text:
Current evaluation of breast health concerns and diagnosis of breast cancer
Issue: BCMJ, vol. 60 , No. 1 , January February 2018 , Pages 27-32	Clinical Articles
By: Amie Padilla-Thornton, MD, FRCPC Jessica Farrell, MD, FRCPC Paula Gordon, MD, FRCPC Akushla Wijayanayagam, MD, FRCSC Rebecca Warburton, MD, FRCSC Amanda Roberts, MD, MPH, FRCSC Connie G. Chiu, MD, FRCSC Sonia Cader, MD, FRCSC F. Michelle Sutter, MD, FRCSC Christopher Baliski, MD, FRCSC Rona E. Cheifetz, MD, MEd, FRCSC, FACS Elaine McKevitt, MD, MEd, FRCSC, FACS
ABSTRACT: The process leading to diagnosis of breast cancer has changed over the past 20 years with improvements in diagnostic imaging and a shift from surgical biopsy to image-guided core needle biopsy. History-taking and physical examination, diagnostic breast imaging, and biopsy are essential when evaluating breast concerns, as is the use of the Breast Imaging Reporting and Data System (BI-RADS) when describing findings. Assessment of the concordance between physical examination findings, imaging, and biopsy pathology is also essential to diagnosis, and minimizes surgical intervention. The roles of the primary care physician, radiologist, and surgeon have changed as well over the past 20 years, meaning that the optimal management of patients with breast concerns is now multidisciplinary. Referring physicians have different roles in navigating patients through the diagnostic system in different communities.
Physical examination, diagnostic breast imaging, and image-guided core needle biopsy are essential when evaluating breast complaints, as is the use of the Breast Imaging Reporting and Data System (BI-RADS) when describing findings.
The evaluation of breast health concerns and the diagnosis of breast cancer have changed significantly over the past 20 years due to advances in imaging technology and pathology techniques as well as increased interdisciplinary management of breast problems.
The referral pathways for diagnostic breast imaging address both the evaluation of a presenting breast complaint in the symptomatic patient and the evaluation of an abnormality identified on screening mammography in an asymptomatic patient. The diagnostic imaging workup for each requires careful risk assessment, use of the Breast Imaging Reporting and Data System (BI-RADS) lexicon, and concordance assessment of the physical examination, imaging, and pathology results. If these components of the patient's workup are not concordant, further investigation is necessary to rule out malignancy.
History and physical examination
When patients present with breast concerns, a detailed clinical history should be obtained and a physical examination performed to clarify the symptoms and physical findings and determine the need for further investigation with diagnostic breast imaging. Palpable lumps or areas of thickening, nipple discharge, and breast pain are among the most common presenting complaints.
A lump or area of thickening should be assessed for any features of concern for breast cancer, such as hard or irregular texture and apparent fixation to the chest wall, as well as any associated nipple discharge, overlying skin or nipple changes, and the presence of palpable axillary or supraclavicular lymphadenopathy.
Physiologic nipple discharge should be differentiated from pathologic nipple discharge. Physiologic discharge is bilateral, involves multiple ducts, is milky/yellow/green in color, and is nonspontaneous. This type of discharge does not require diagnostic medical imaging. Pathologic discharge is unilateral, involves a single duct, is clear/bloody/serosanguinous in color, and is spontaneous.
A physical examination is the first step in the evaluation of breast pain. The location and characteristics of the pain help to differentiate breast pain from chest wall pain. Chest wall pain is commonly located at the costochondral junctions and over the lateral chest wall rather than in the breast itself. Physiologic breast pain is characterized as cyclical, nonfocal, and bilateral, and is typically due to hormonal or age-related changes. Physiologic breast and chest wall pain do not require diagnostic breast imaging as pain of this nature has not been shown to correlate with the presence of breast cancer.[1] Breast pain that is persistent, noncyclical, unilateral, and, most importantly, focal, may indicate underlying breast pathology.
Diagnostic breast imaging is indicated when a palpable breast lump or thickening, suspicious skin changes, pathologic nipple discharge, or focal breast pain are confirmed on physical examination. In the absence of suspicious physical examination findings, screening mammography is recommended.
If an abnormality is identified on screening mammography, a physical examination of the breast should be performed to determine if the finding is image-detected only or associated with findings on examination. Ideally, breast examination should occur prior to a core needle biopsy (CNB) to allow for accurate clinical assessment of the abnormality in question.
Diagnostic breast imaging
There are several reasons a patient may be referred for diagnostic breast imaging. This specialized imaging is used to evaluate a physical examination finding or to further characterize an abnormality identified on a screening mammogram in an asymptomatic patient. In addition, diagnostic breast imaging should be scheduled on a routine surveillance basis for patients with breast prostheses and previously treated breast cancers or high-risk lesions.
Bilateral diagnostic mammography and targeted ultrasound focused on the area of clinical concern are used to evaluate the majority of breast health concerns. Digital breast tomosynthesis, a form of 3-D or volumetric mammography, is becoming increasingly available for use in diagnostic breast imaging and permits better differentiation between normal and abnormal tissue.[2] Magnetic resonance imaging (MRI) may be used in limited circumstances, such as for screening patients with a known BRCA1 or BRCA2 mutation or a history of mantle radiation between age 10 and 30, for assessment of breast prostheses that may have ruptured, for assessment of indeterminate lesions, for assessment of pathologic nipple discharge, and for staging of breast cancers, particularly if there is multifocality or lobular histology.[3]
Categories of risk
The Breast Imaging Reporting and Data System,[4] published by the American College of Radiology (ACR) and summarized in (Table 1), provides standardized descriptions of findings that communicate the likelihood of breast cancer based on the imaging workup. The BI-RADS assessment of risk ultimately determines the need for an image-guided needle biopsy.
Patients with imaging studies categorized as BI-RADS 1 (negative) or BI-RADS 2 (conclusively benign) do not require further imaging workup. Lesions assessed as BI-RADS 3 have an estimated malignancy risk of less than 2% and follow-up imaging is recommended at 6, 12, and 24 months to ensure stability. Lesions assessed as BI-RADS 4 have an estimated malignancy risk of between 2% and 95% and biopsy is recommended. With this large range of risk, many radiologists subdivide BI-RADS 4 into three categories based on positive predictive values: 4A (less than 2% to less than or equal to 10% risk), 4B (greater than 10% to less than or equal to 50% risk), and 4C (greater than 50% to less than or equal to 95% risk). Lesions assessed as BI-RADS 5 have an estimated risk of malignancy greater than 95%, require core needle biopsy, and should have surgical excision even if the pathology from the biopsy does not confirm malignancy.
During the diagnostic breast imaging appointment, the radiologist will integrate elements from this detailed assessment by correlating the findings on the different imaging modalities. The radiologist will then prepare a report providing a final BI-RADS assessment score and guidance. Typically, the report will make one of five recommendations:
1. The imaging is incomplete and has not as yet permitted thorough assessment of the presenting clinical concern (BI-RADS 0). Additional imaging is required with final management options to be detailed in a subsequent report.
2. The findings are negative (BI-RADS 1) or benign (BI-RADS 2) and the patient can be discharged from undergoing further diagnostic breast imaging. If the patient is older than 40, routine screening mammography will be recommended.
3. The findings are estimated to have a greater than 98% likelihood of being benign (BI-RADS 3) and follow-up imaging in 6, 12, and 24 months is required to demonstrate stability, at which point the findings will be considered definitively benign.
4. An abnormality identified is estimated to have a greater than 2% likelihood of being malignant (BI-RADS 4 or BI-RADS 5), and an image-guided biopsy is required for definitive pathologic diagnosis.
5. Depending on the presenting compliant, referral to a breast specialist or surgeon may be recommended.
A very small subset of breast cancers will not be detected on a mammogram or breast ultrasound, and negative findings on imaging should not be cause for a delay in diagnosis of breast cancer. Any suspicious findings from a physical examination require further imaging and biopsy. In this situation, referral to a surgeon is advised.
Image-detected breast abnormalities
Nonpalpable breast lesions (masses, calcifications, asymmetries, and architectural distortion) can be identified on screening mammograms as well as incidentally on diagnostic breast imaging done for other indications. The evaluation of such abnormalities focuses on assessing the risk for malignancy. Patients should have an examination to determine whether there is an associated physical finding; however, in cases where there are no associated physical findings to guide the treating clinician, the BI-RADS reporting system and radiology-pathology concordance statements are particularly useful in determining the need for further management and follow-up.
Core needle biopsy
Core needle biopsy (CNB) of breast lesions is the preferred initial invasive diagnostic procedure,[5-9] and image guidance by ultrasound, mammography, or MRI is recommended to increase the accuracy of targeting.[8,10] CNB is able to accurately diagnose most breast lesions and results in an improved cosmetic outcome for the patient and cost savings to the health care system. As well, CNB can decrease the number of operations that a patient requires.[7,8] CNB is safe and does not cause dissemination of cancer.[7]
The guidance modality chosen depends on the conspicuity of the lesion. Most masses are seen clearly on ultrasound, and can therefore be biopsied with ultrasound guidance. For lesions seen on mammography, but not visible on ultrasound, biopsy with stereotactic or tomosynthesis guidance is used. Either way, the procedures are well tolerated under local anesthesia. CNB of breast lesions is now the standard of care and surgical biopsy should be performed only when core needle biopsy is not possible.[5-9,11] Obtaining preoperative core needle biopsy diagnoses of breast lesions in more than 90% to 95% of patients is a quality indicator in breast surgery internationally.[5,6,9] CNB pathology results are classified as benign, high-risk, or malignant.[8,12]
Concordance assessment
Concordance assessment is an integral part of core needle biopsy. For an image-guided CNB, "concordance refers to the agreement of imaging and histopathological findings such that the histopathology satisfactorily explains the imaging findings."[12,13] Discordance refers to occasions when a breast CNB demonstrates benign histology while the imaging findings indicate possible malignancy. Discordance indicates that further evaluation is required, with options including (1) repeating CNB, possibly with a larger gauge or vacuum-assisted device, (2) surgical excisional biopsy, or (3) clinical and imaging surveillance.[8,12]
Failure to resolve discordance between radiology and pathology results can lead to a delay in breast cancer diagnosis. The specifics of radiologic-pathologic correlation should be provided by the radiologist performing the biopsy,[12,13] and this is typically done by issuing a radiology-pathology addendum report that includes the histopathologic diagnosis and outlines whether further investigation, follow-up, surgical excision, or multidisciplinary review is recommended.
For symptomatic patients, there should be correlation with the physical examination findings, diagnostic breast imaging, and pathology[12] by the clinician who has ordered and reviewed the investigations. If the physical examination results remain suspicious for malignancy, but imaging and/or core needle biopsy results are benign, further investigations such as skin biopsy, surgical biopsy, repeat core needle biopsy, or further imaging are necessary to rule out malignancy.
Borderline or high-risk lesions
Concordance assessment also involves assessing the risk of undersampling, which refers to the possibility of missing a significant finding in the adjacent tissue that was not removed by the CNB. When there is a significant probability of undersampling, the lesion is regarded as a borderline or high-risk lesion. Surgical excision of the area is typically recommended for high-risk lesions found on CNB to rule out malignancy. The risk of undersampling varies by diagnosis and is affected by factors such as the number and size of CNB specimens taken, the size of the lesion, and the institution.[8,12] The high-risk lesions for which surgical excision is usually recommended are shown in (Table 2). Institutions that have documented a low upgrade-to-breast-cancer rate following surgical resection for specific diagnoses may offer their patients short-term imaging follow-up rather than surgical excision.[8,12,14]
After surgical excision
Concordance assessment is recommended after surgical excision of breast lesions to ensure that the lesion of interest has been accurately targeted and adequately sampled. For image-detected abnormalities, specimen imaging of fine-wire-guided excisions is recommended and all breast surgical specimens should be oriented for the pathologist. In rare circumstances, the lesion localized for surgery with palpation or wire placement is different from the lesion biopsied under imaging guidance, and this is suggested by discordance between preoperative CNB pathology and surgical pathology. The presence of the CNB scar in the tissue excised suggests accurate targeting, but scarring can also be present in adjacent tissue. Discordance between the surgical pathology and the preoperative diagnosis indicates further investigations are required, usually further imaging, with possible repeat image-guided localization and surgical re-excision. Multidisciplinary review is recommended to guide management.
Navigating the diagnostic system
With the development of more options for diagnostic breast imaging and the introduction of image-guided breast biopsy, patients may need to attend several appointments to complete their imaging workup. It is recommended that patients have their mammograms, breast ultrasound, and image-guided core needle biopsies performed by a single radiology group to facilitate comparison, limit duplication of examinations, and decrease wait times. When more specialized biopsy or imaging techniques are required, such as stereotactic core biopsy or MRI-guided biopsy, the patient may be referred to a different facility as access to these services is not universally available. All relevant imaging and reports, as well as any pathology reports, should be forwarded when a patient is referred to a new facility.
The potential for fragmented care and extended wait times has been recognized.[15,16] The 2012 Provincial Breast Health Strategy Summary Report[16] recommended a target wait time of 21 days to diagnosis without biopsy and a wait time of 28 days to diagnosis when biopsy is required. The report also recommended facilitating necessary investigations and increasing navigation resources for patients to achieve the goal of a prompt diagnosis. The Screening Mammography Program of BC introduced fast track booking for evaluation of screen-detected lesions in 2010,[17] and many breast diagnostic teams in the province have introduced care pathways and dedicated breast health clinics in an attempt to reduce wait times.[18,19]
Currently, each community has a slightly different system for arranging breast imaging and biopsies. Additional investigations are facilitated either by radiology or by the ordering physician, depending on the centre. With so many different approaches and pathways, problems can arise, particularly if patients have mammograms outside of their usual community or health authority. Referring physicians should be aware of these differences and the role they are expected to play in arranging investigations and follow-up for their patients.
Methodical evaluation of breast health concerns is essential to ensure completion of a thorough imaging and pathology assessment in an appropriate time frame. This allows for malignancy to be excluded and the patient returned to the care of the referring physician, or for malignancy to be confirmed and definitive treatment arranged. The BI-RADS lexicon is needed to communicate the likelihood of malignancy in a standardized way, while concordance assessments between the clinical presentation, imaging results, and final pathology are crucial and should be employed throughout the evaluation. Finally, because of slight variations in local practice, referring physicians should be aware of the role they play in helping patients navigate the diagnostic system.
The authors would like to acknowledge the BC Cancer Surgical Oncology Network for facilitating a series of meetings for surgeons from all health authorities. We would also like to thank Dr Stacey Piche, a radiologist in Penticton, Dr Karen Seland, a radiologist in Prince George, and Dr Elaine Wai, a radiation oncologist in Victoria, for reviewing the article and participating in our discussions of current diagnostic evaluation of breast problems.
This article has been peer reviewed.
1. American College of Radiology. ACR appropriateness criteria: Breast pain. Accessed 10 March 2017. https://acsearch.acr.org/docs/3091546/Narrative.
2. Hooley RJ, Durand MA, Philpotts LE. Advances in digital breast tomosynthesis. AJR Am J Roentgenol 2017;208:256-266.
3. BC Cancer. Clinical indications for breast MRI. Reviewed July 2009. Accessed 30 July 2016. www.bccancer.bc.ca/health-professionals/clinical-resources/cancer-manage...(Magnetic-Resonance-Imaging).
4. Sickles EA, D'Orsi CJ, Bassett LW, et al. ACR BI-RADS Mammography. In: ACR BI-RADS Breast Imaging Reporting and Data System. 5th ed. Reston, VA: American College of Radiology, 2013.
5. Del Turco MR, Ponti A, Bick U, et al. Quality indicators in breast cancer care. Eur J Cancer 2010;46:2344-2356.
6. American College of Surgeons. National accreditation programs for breast centers. Accessed 2 August 2016. www.facs.org/~/media/files/quality%20programs/napbc/2014%20napbc%20stand...
7. Cho K, Tyldesley S, Speers C, et al. The utilization and impact of core needle biopsy diagnosis on breast cancer outcomes in British Columbia. BCMJ 2014;56:183-190.
8. Silverstein M, Recht A, Lagios M, et al. Special report: Consensus conference III. Image-detected breast cancer: State-of-the-art diagnosis and treatment. J Am Coll Surg 2009;209:504-520.
9. American Society of Breast Surgeons. Measure #263: Preoperative diagnosis of breast cancer—national quality strategy domain: Effective clinical care. Accessed 4 September 2016. www.breastsurgeons.org/statements/QM/ASBrS_Preoperative_diagnosis_of_bre....
10. American Society of Breast Surgeons. Position statement on image-guided percutaneous biopsy of palpable and nonpalpable breast lesions. Accessed 1 August 2016. www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Image-....
11. American Society of Breast Surgeons. Performance and practice guidelines for excisional breast biopsy. Approved 2014. Accessed 4 September 2016. www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Perfor....
12. American Society of Breast Surgeons. Consensus guideline on concordance assessment of image-guided breast biopsies and management of borderline and high-risk lesions. Accessed 9 January 2017. www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Concor...
13. American College of Radiology. ACR practice parameter for the performance of ultrasound-guided percutaneous breast interventional procedures. Revised 2016. Accessed 19 March 2017. www.acr.org/~/media/ACR/Documents/PGTS/guidelines/US_Guided_Breast.pdf.
14. Becker AK, Gordon PB, Harrison DA, et al. Flat ductal intraepithelial neoplasia 1A diagnosed at stereotactic core needle biopsy: Is excisional biopsy indicated? AJR Am J Roentgenol 2013;200:682-628.
15. Poole B, Gelmon K, Borugian M, et al. Breast cancer screening and diagnosis in British Columbia. BCMJ 2008;50:198-205.
16. Pelletier L. Breast health strategy summary report 2012. Provincial Health Services Authority.
17. Borugian MJ, Kan L, Chu CC, et al. Facilitated "fast track" referral reduces time from abnormal screening mammogram to diagnosis. Can J Public Health 2008;99:252-256.
18. Baliski C, McGahan CE, Liberto CM, et al. Influence of nurse navigation on wait times for breast cancer care in a Canadian regional cancer center. Am J Surg 2014;207:686-691;discussion 691-692.
19. McKevitt EC, Dingee CK, Leung S, et al. Reduced time to breast cancer diagnosis with coordination of radiological and clinical care. Cureus. Published online 7 December 2017. www.cureus.com/articles/9947-reduced-time-to-breast-cancer-diagnosis-wit....
Drs Padilla-Thornton, Farrell, and Gordon are radiologists in Vancouver. Drs Padilla-Thornton and Farrell are also clinical instructors in the Department of Radiology at UBC, and Dr Gordon is a clinical professor. Dr Wijayanayagam is a surgeon in BC and Dr Roberts is a surgeon in Ottawa, and both are associated with the BC Cancer Surgical Oncology Network. Drs Warburton, Chiu, Cader, Sutter, Baliski, Cheifetz, and McKevitt are surgeons in BC associated with the BC Cancer Surgical Oncology Network. As well, Drs Chiu and Cader are clinical instructors in the Department of Surgery at UBC; Drs Baliski, Warburton, and Sutter are clinical assistant professors; Dr Cheifetz is an associate professor; and Dr McKevitt is a clinical associate professor.
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Amie Padilla-Thornton, MD, FRCPC, Jessica Farrell, MD, FRCPC, Paula Gordon, MD, FRCPC, Akushla Wijayanayagam, MD, FRCSC, Rebecca Warburton, MD, FRCSC, Amanda Roberts, MD, MPH, FRCSC, Connie G. Chiu, MD, FRCSC, Sonia Cader, MD, FRCSC, F. Michelle Sutter, MD, FRCSC, Christopher Baliski, MD, FRCSC, Rona E. Cheifetz, MD, MEd, FRCSC, FACS, Elaine McKevitt, MD, MEd, FRCSC, FACS. Current evaluation of breast health concerns and diagnosis of breast cancer. BCMJ, Vol. 60, No. 1, January, February, 2018, Page(s) 27-32 - Clinical Articles.
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Here I watched Game of Thrones season 8 first episode
I hope Amazon publishes it at 2100 EDT (UTC -0500) like they did last year. Gotta love those WEB-DLs before the episode even finishes airing on HBO. And Amazon is pretty close to Blu-ray quality in terms of video to my eyes.
Anyway, for anyone in the U.S. with cable, IPTV, and/or satellite TV HBO has a free weekend for this weekend including Sunday if the WEB-DL isn't up that night so if you're really impatient you can just watch it through your set top box. I am unsure which TV providers are participating besides my own (Cincinnati Bell).
I'd recommend waiting though because U.S. TV is bitrate starved trash. Either decades old MPEG2 or worse MPEG2 transcoded in the most shitty way possible to H.264 by some IPTV or sat providers.
HBO has now revealed the exact length of all six episodes.
The network has updated its TV schedule to reveal that the opening episode, which airs on April 14, will be 54 minutes long, while the second instalment, airing on April 21, will be 58 minutes long.
It's also confirmed that episode three is a whopping 82 minutes, contrary to previous information taken from its online schedule that had it down at a measly 60 minutes.
Episode four is 78 minutes, and the final two episodes are a hefty 80 minutes each.
Benioff and Weiss have written almost every episode for the entire show themselves. They don't seem to be interested in getting too many other people on board (which is a shame, because Bryan Cogman, one of the few other writers on the show, has fairly consistently shown a respect for the source material which D&D have increasingly lacked).
Episode 1 (click here) showed that they're capable of strong, competent writing when they stick closely to what GRRM has laid out, but with every passing season since, they've shown that they really struggle whenever they go off on their own (whether the deviation is by necessity (as with recently, where they only have the endgame, but not the actual path there, and have to invent the path from scratch, more or less) or by choice (where they decide they just don't give a shit about the books and want to write their own fan-fiction; too many examples of that to bother listing)).
I did still enjoy this episode though (except, as I mentioned, for the stupid shit they're doing with Sansa and Arya), but I do agree that this episode has really highlighted something which D&D have struggled with continuously over the course of the show, which is: the existence of geography and the passage of time. Which is kind of ironic; they chose to make the opening credits of the show a map of Westeros which they then proceed to ignore. (It's baffling that it took them as long as it did to get where they were, but then Gendry seemed to make it back to Castle Black in a relatively short amount of time (although, again!, it's almost impossible to measure time in this show); also, while I know little and less of the speed of ravens, it seems the raven made it from Castle Black to Dragonstone pretty fast; but that particular point is one that would probably take more calculation to work out than it's worth, so eh)
Or just enter on 123movies here and search it, or find it fast on featured area.
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Research | Open | Published: 31 October 2007
Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study
Borislav A Alexiev1,
Wenle Wang1,
Yi Ning1,
Saranya Chumsri2,
Ivana Gojo2,
William H Rodgers1,
Sanford A Stass1 &
Xianfeng F Zhao1
Context. -
Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate.
Objective. -
To evaluate the lineage differentiation of neoplastic cells in MS by immunohistochemistry, and to correlate the results with clinicopathologic findings and cytogenetic studies.
Design. -
Histologic and immunohistochemical examinations were performed on formalin-fixed paraffin-embedded tissue samples from 13 cases of MS. They were classified according to the World Health Organization criteria. Chromosomal analysis data were available in 11 cases. Clinical, pathological, and cytogenetic findings were analyzed.
Results. -
The study included six male and seven female patients with an age range of 25 to 72 years (mean, 49.3 years) and a male to female ratio of 1:1.2. MS de novo occurred in 4/13 (31%) of cases examined. The most sensitive immunohistochemical markers were CD43 and lysozyme present in all cases with MS (13/13, 100%). All de novo MS showed a normal karyotype, monoblastic differentiation, and lack of CD34. The most common chromosomal abnormalities in MS associated with a hematopoietic disorder were trisomy 8 and inv(16) (2/11, 18%).
Conclusion. -
An immunohistochemical panel including CD43, lysozyme, myeloperoxidase (MPO), CD68 (or CD163), CD117, CD3 and CD20 can successfully identify the vast majority of MS variants in formalin-fixed paraffin-embedded tissue sections. The present report expands the spectrum of our knowledge showing that de novo MS has frequent monoblastic differentiation and frequently carries a normal karyotype.
Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site or in the bone [1]. The tumor can involve any part of the body, but commonly involved sites include subperiosteal bone structures of the skull, paranasal sinuses, sternum, ribs, vertebrae, and pelvis; lymph nodes and skin are also common sites [1]. MS may occur de novo or concurrently with acute myeloid leukemia (AML) or a myeloproliferative disorder [1]. The rate of occurrence is approximately 1.4% to 9% of patients with AML [2, 3]. MS is frequently mistaken for non-Hodgkin lymphoma (NHL), small round cell tumor (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma/PNET, and medulloblastoma), and undifferentiated carcinoma. The diagnosis is missed in about 50% of cases when immunohistochemistry is not used [4]. The most common suggested diagnosis was that of a NHL [5].
The present study was designated to evaluate the lineage differentiation of neoplastic cells in MS by immunohistochemistry, and correlate the results with clinicopathologic findings and cytogenetic studies.
Thirteen patients with a histologic diagnosis of myeloid sarcoma were included in the present study. The initial diagnosis was made on core biopsies (3 cases) and surgical specimens (10 cases). The specimens were fixed in 10% formaldehyde and embedded in paraffin. Five-micron tissue sections were stained with hematoxylin-eosin. The use of paraffin blocks for this study meets Institutional Review Board and Health Insurance Portability and Accountability Act requirements, and has been approved by the Institutional Review Board at the University of Maryland.
Immunohistochemical staining was performed using an automated slide preparation system (Benchmark XT, Ventana, Tuscon, AZ), a Ventana Enhanced DAB Detection Kit (Ventana, Tucson, AZ), and commercially available prediluted monoclonal antibodies: CD163 (NeoMarkers), CD4 (Biocare Medical), myeloperoxidase, lysozyme, CD3, CD4, CD8, CD15, CD20, CD34, CD43, CD68, CD79a, CD117, Factor VIII (FVIII), and glycophorin A (all Ventana, Tucson, AZ).
Chromosomal Study
Chromosomal analysis was performed on tumor specimens from 11 patients at diagnosis. Cells were cultured in RPMI 1640 medium with 20% fetal bovine serum for 24 and 48 hours, respectively. Metaphase cells were analyzed following standard G-banding method. Their karyotypes were interpreted according to the International System for Human Cytogenetic Nomenclature.
The clinical findings are shown in Table 1. The study included six male and seven female patients with an age range of 25 to 72 years (mean, 49.3 years) and a male to female ratio of 1:1.2. MS de novo occurred in 4/13 (31%) cases examined.
Table 1 Clinical findings in patients with myeloid sarcoma
Sites of involvement
MS occurred in a variety of extramedullary sites (Table 1). Nine of thirteen cases with MS (69%) had a synchronous involvement of the bone marrow by acute leukemia, myeloproliferative, or myelodysplastic disorder.
Histology and immunohistochemistry
The pathologic diagnoses are shown in Table 2.
Table 2 Pathologic diagnosis in patients with myeloid sarcomas
Immature granulocytic sarcomas (IGS) were characterized by the presence of numerous (> 90%) blasts with high N/C ratio, round or oval nucleus, dispersed chromatin and prominent nucleolus. The cytoplasm of the majority of neoplastic cells was agranular with a varying degree of basophilia. Eosinophilic granulation was notable in a minority of a cell population. The neoplastic cells in IGS showed reactivity with CD34, CD43, CD117, and lysozyme. MPO was present in a variable number of blasts, but always <10%. Focal weak reactivity of the neoplastic cells with antibodies to CD68 and/or CD163 was also noted. Differentiated granulocytic sarcomas (DGS) showed maturation to more mature neutrophils (>10% of neoplastic cells). The neoplastic cells in DGS showed strong reactivity with CD43, MPO, CD15, lysozyme, and variably expressed CD117. CD68 and CD163 were positive in <20% of neoplastic cells.
Monoblastic sarcomas (MBLS) were composed of a large population (> 80%) of monoblasts. The neoplastic cells were large, with abundant eosinophilic cytoplasm, round or oval nuclei with dispersed chromatin and one or more prominent nucleoli. Promonocytes showed more irregular, delicately convoluted nuclear features. MBLS were strongly positive for CD43, lysozyme, CD68, CD163, weakly for CD4, and negative for CD34. Scattered MPO positive cells were also noted (Figs. 1, 2, 3, 4, 5, 6, 7).
Monoblastic sarcoma de novo, skin. (hematoxylin-eosin, × 100).
Monoblatic sarcoma de novo, skin. Multiple mitotic figures are seen. (hematoxylin-eosin, × 400).
Monoblastic sarcoma de novo. Neoplastic cells are positive for CD43. (B-SA, anti-CD43, × 400).
Monoblastic sarcoma de novo. Neoplastic cells are positive for CD163. (B-SA, anti-CD163, × 400).
Monoblastic sarcoma de novo. Neoplastic cells are negative for CD3. Residual T-lymphocytes are positive with CD3 antibody. (B-SA, anti-CD3, × 400).
Monoblastic sarcoma de novo. One single neoplastic cell is positive for MPO. (B-SA, anti-MPO, × 400).
Monoblastic sarcoma de novo. Neoplastic cell are negative for CD34. Stain for CD34 reveals endothelial cells. (B-SA, anti-CD34, × 400).
In monocytic sarcoma (MCS), the majority of neoplastic cells showed marked nuclear lobulation and stained strongly with antibodies to CD43, lysozyme, CD68, CD163, and variably with MPO (Figs. 8, 9, 10, 11).
Monocytic sarcoma, gallbladder. (hematoxylin-eosin, × 100).
Monocytic sarcoma, gallbladder. Neoplastic cells have very dispersed chromatin and inconspicuous nucleoli. Note irregular and delicately convoluted nuclear configuration. (hematoxylin-eosin, × 400).
Monocytic sarcoma, gallbladder. Neoplastic cells are positive for CD43. (B-SA, anti-CD43, × 400).
Myelomonocytic sarcomas (MMS) were characterized by proliferation of both neutrophilic and monocytic precursors with above described morphologic and immunohistochemical features each comprising >20% of neoplastic cells. The cases were notable for increased numbers of eosinophils containing large eosinophilic granules in the cytoplasm.
The neoplastic cells in all MS examined did not react with antibodies to FVIII, and glycophorin A. T and B lymphocyte lineage-specific antigens such as CD3, CD20, and CD79a were typically absent.
All MS were morphologically and immunophenotypically analogous to their leukemic counterparts.
The cytogenetic findings are shown in Table 3. Chromosomal abnormalities were observed in 6/11 (55%) cases examined. All patients with MS occurring de novo had a normal karyotype (4/4, 100%). The most common genetic abnormalities were the presence of an extra chromosome 8 and inv(16) (2/11, 18%) (Fig. 12).
Monocytic sarcoma, gallbladder. Chromosomal analysis reveals trisomy 8 and trisomy 13. (standard G-banding)
Table 3 Cytogenetic findings in patients with myeloid sarcoma
MS is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site [6]. The neoplasm usually occurs in patients with acute myeloid leukemia, myelodysplastic or myeloproliferative disorder. It may rarely precede peripheral blood or bone marrow involvement, presenting a diagnostic challenge. In our study, all patients were adults with a slight female predominance. In agreement with previous reports, the neoplasms occurred in different locations including the orbit, gingiva, skin, breast, vertebral bodies, GI tract, and genito-urinary system. [6–16].
With extensive morphological and immunohistochemical analyses, the MS were classified into five types: a) immature granulocytic sarcoma (IGS); b) differentiated granulocytic sarcoma (DGC); c) monoblastic sarcoma (MBLS); d) monocytic sarcoma (MS), and myelomonocytic sarcoma (MMS) (Table 2). These tumors were also morphologically and immunophenotypically analogous to their leukemic counterparts. In agreement with previous reports [5], CD43 and lysozyme were the most sensitive markers staining a large proportion of neoplastic cells in all tumors examined (13/13, 100%). MPO and CD117 were the most sensitive of the markers for myeloid differentiation while monocytic precursors consistently strongly expressed CD68 and CD163. Differential diagnosis of MS includes several entities, the majority of which can be readily distinguished using a combination of morphologic and immunohistochemical evaluation. MS is frequently mistaken for malignant B-cell or T-cell lymphoma, especially when it presents without leukemic manifestation [3]. An incomplete workup may be misleading because NHL and MS share morphologic similarities and both express some leukocyte antigens, such as CD43 and CD45. In our study, B-cell and T-cell lymphomas were excluded by negative stains for CD20, CD79a and CD3, respectively. In addition, blastic NK cell lymphoma can mimic IGS, or MBLS. The neoplastic cells consistently express CD43, CD4, CD56, and, unlike MS, are negative for MPO, CD33, CD117, lysozyme, and CD68. Burkitt lymphoma could be excluded by negative immunoreactivity for B-cell-associated antigens, a relatively low proliferation rate, and lack of t(8;14) or t(2;8), and t(8;22) translocations.
The findings are in agreement with previous observations and suggest that an immunohistochemical panel including CD43, MPO, CD117, CD68 (or CD163), CD3 and CD20 can successfully identify the majority of MS in formalin-fixed, paraffin-embedded tissue specimens [17–22]. Using the antibody panel mentioned above, we reached the correct diagnosis in all cases examined. In cases with megakaryoblastic and/or erythroblastic differentiation, diagnosis can be confirmed by inclusion of one or more lineage-specific markers, such as FVIII, CD41, CD61, glycophorin A, and hemoglobin A in the diagnostic panel [1, 23].
MS has been described in association with a variety of chromosomal abnormalities [1, 24]. In particular, t(8;21)(q22;q22) and inv(16) are regarded as recurrent aberrations in GS [1, 3, 9, 15] while translocations involving 11q23 have been detected in MBLS [1]. In this study, chromosomal aberrations were detected in 55% (6/11) of the cases. The commonest abnormalities were +8, and inv(16) occurring in 18% (2/11) of MS. DGS (n = 1) and MCS (n = 1) carried trisomy 8 (n = 1) while inv(16) was observed in IGS (n = 1) and MMS (n = 1). The findings support the recent observation of Deeb et al. [24] who described chromosome 8 abnormalities as the most common genetic aberration in MS. In this study, all cases carrying chromosomal abnormalities (6/6, 100%) had simultaneous AML, myeloproliferative disorder or MDS. Similar to what was reported by others [25], we found that inv(16) was associated with myelomonocytic differentiation in at least one case. Inv(16) was also identified in another case that was classified as IGS with multiple cytogenetic abnormalities. Furthermore, both cases involved the breast, in contrast to earlier reports of intestinal involvement by inv(16) positive MS with monocytic differentiation. All patients with de novo MS showed a normal karyotype (4/4, 100%), monoblastic differentiation, and lack of CD34. Previous studies revealed a correlation of monocytic differentiation, lack of CD34, and normal cytogenetics with nucleophosmin gene (NPM1) abnormalities [26]. In adults, NPM1 gene mutations have been identified in 50% to 60% of all AML cases with a normal karyotype [26]. Whether this newly identified molecular marker can aid in stratification of patients is under clinical investigation. In addition, a recent study showed a significant correlation between extramedullary involvement and coexpression of MCP-1/CCR2 by M4–M5 blasts which might help to explain some aspects of the pattern of invasion in MS with monocytic differentiation [27].
The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate [7]. Previous studies have indicated that the biologic behavior is dramatic irrespective of presentation, age, sex, phenotype and cytogenetics [25]. Conversely to that reported by Pileri et al. [25], other reports showed a shorter median survival of patients with chromosome 8 abnormalities [2] and better prognosis for patients with GS [9]. From our experience, the occurrence of GS in patients with hematological abnormalities has a negative impact on median survival and prognosis (unpublished observations).
The present report expands the spectrum of our knowledge showing that de novo MS has frequent monoblastic differentiation and frequently carries a normal karyotype. The most common genetic aberrations in MS associated with hematopoietic disorders were trisomy 8 and inv(16).
Brunnung RD, Matutes E, Flandrin G, Vardiman J, Bennett J, Head D, Harris NL: Acute myeloid leukemias. World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Edited by: Jaffe ES, Harris NL, Stein H, Vardiman JW. 2001, IARC Press, 77-105.
Tsimberidou AM, Kantarjian HM, Estey E, Cortes JE, Verstovsek S, Faderl S, Thomas DA, Garcia-Manero G, Ferrajoli A, Manning JT, Keating MJ, Albitar M, O'Brien S, Giles FJ: Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia. 2003, 17: 1100-1103. 10.1038/sj.leu.2402958.
Zekry N, Klooster MJ, Raghavan R, Wang J: A 7-year-old child with a history of acute myeloid leukemia presenting with multiple gastrointestinal polyps. Arch Pathol Lab Med. 2006, 130: 3-4.
Audouin J, Comperat E, Le Tourneau A, Camilleri-Broet S, Adida C, Molina T, Diebold J: Myeloid sarcoma: clinical and morphological criteria useful for diagnosis. Int J Surg Pathol. 2003, 11: 271-282. 10.1177/106689690301100404.
Menasce LP, Banerjee SS, Beckett E, Harris M: Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases. Histopathol. 1999, 34: 391-398. 10.1046/j.1365-2559.1999.00651.x.
Valbuena JR, Admirand JH, Gualco G, Medeiros LJ: Myeloid sarcoma involving the breast. Arch Pathol Lab Med. 2005, 129: 32-38.
Colella G, Tirelli A, Capone R, Rubini C, Guastafierro S: Myeloid sarcoma occuring in the maxillary gingiva: a case without leukemic manifestations. Int J Hematol. 2005, 81: 138-41. 10.1532/IJH97.E0410.
Antmen B, Haytac MC, Sasmaz I, Dogan MC, Ergin M, Tanyelli A: Granulocytic sarcoma of gingival: an unusual case with aleukemic presentation. J Periodontol. 2003, 74: 1514-1519. 10.1902/jop.2003.74.10.1514.
Stein-Wexler R, Wootton-Gorges SL, West DC: Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia. Pediatr Radiol. 2003, 33: 136-139.
Ojima H, Hasegawa T, Matsuno Y, Sakamoto M: Extramedullary myeloid tumour (EMMT) of the gallbladder. J Clin Pathol. 2005, 58: 211-213. 10.1136/jcp.2004.019729.
Yavuz S, Paydas S, Disel U, Erdogan S: Ovarian granulocytic sarcoma. Leuk Lymphoma. 2004, 45: 183-185. 10.1080/10428109031000149331.
Oliva E, Ferry JA, Young RH, Prat J, Srigley JR, Scully RE: Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases. Am J Surg Pathol. 1997, 21: 1156-1165. 10.1097/00000478-199710000-00005.
Valbuena JR, Admirand JH, Lin P, Medeiros LJ: Myeloid sarcoma involving the testis. Am J Clin Pathol. 2005, 124: 445-452. 10.1309/NXLC-J1B1-6YDF-QWND.
Garcia MG, Deavers MT, Knoblock RJ, Chen W, Tsimberidou AM, Manning JT, Medeiros LJ: Myeloid sarcoma involving the gynecologic tract: a report of 11 cases and review of the literature. Am J Clin Pathol. 2006, 125: 783-790.
Al-Quran SZ, Olivares A, Lin P, Stephens TW, Medeiros LJ, Abruzzo LV: Myeloid sarcoma of the urinary bladder and epididymis as a primary manifestation of acute myeloid leukemia with inv(16). Arch Pathol Lab Med. 2006, 130: 862-866.
Gopal S, Marcussen S, Dobin SM, Koss W, Donner LR: Primary myeloid sarcoma of the testicle with t(15;17). Cancer Gen Cytogen. 2005, 157: 148-150. 10.1016/j.cancergencyto.2004.06.010.
Li JM, Liu WP, Zhang MH, Wei X, Gu JM, Han AJ, Wu WQ, Chen XY: Clinicopathologic and immunophenotypic analysis of myeloid sarcoma. Zhonghua Bing Li Xue Za Zhi. 2006, 35: 606-611.
Liu YH, Zhuang HG, Liao XB, Luo XL, Cai XL, Luo DL: Diagnosis and differential diagnosis of granulocytic sarcomas. Zhonghua Xue Ye Xue Za Zhi. 2003, 24: 568-571.
Ritter JH, Goldstein NS, Argenyi Z, Wick MR: Granulocytic sarcoma: an immunohistologic comparison with peripheral T-cell lymphoma in paraffin sections. J Cutan Pathol. 1994, 21: 207-216. 10.1111/j.1600-0560.1994.tb00262.x.
Chang CC, Eshoa C, Kampalath B, Shidham VB, Perkins S: Immunophenotypic profile of myeloid cells in granulocytic sarcoma by immunohistochemistry. Correlation with blast differentiation in bone marrow. Am J Clin Pathol. 2000, 114: 807-811. 10.1309/WWW7-DG6X-HC16-D7J2.
Hudock J, Chatten J, Miettinen M: Immunohistochemical evaluation of myeloid leukemia infiltrates (granulocytic sarcomas) in formaldehyde-fixed, paraffin-embedded tissue. Am J Clin Pathol. 1994, 102: 55-60.
Traweek ST, Arber DA, Rappaport H, Brynes RK: Extramedullary myeloid cell tumors. An immunohistochemical and morphological study of 28 cases. Am J Surg Pathol. 1993, 17: 1011-1019.
Hirose Y, Masaki Y, Shimoyama K, Sugai S, Nojima T: Granulocytic sarcoma of megakaryoblastic differentiation in the lymph nodes terminating as acute megakaryoblastic leukemia in a case of chronic idiopathic myelofibrosis persisting for 16 years. Eur J Hematol. 2001, 67: 194-198. 10.1046/j.0902-4441.2001.492umedoc.492.x.
Deeb G, Baer MR, Gaile DP, Sait SN, Barcos M, Wetzler M, Conroy JM, Nowak NJ, Cowell JK, Cheney RT: Genomic profiling of myeloid sarcoma by array comparative genomic hybridization. Genes Chromosomes Cancer. 2005, 44: 373-383. 10.1002/gcc.20239.
Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, Piccaluga PP, Agostinelli C, Asioli S, Novero D, Bisceglia M, Ponzoni M, Gentile A, Rinaldi P, Franco V, Vincelli D, Pileri A, Gasbarra R, Falini B, Zinzani PL, Baccarani M: Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007, 21: 340-350. 10.1038/sj.leu.2404491.
Chen W, Rassidakis GZ, Medeiros LJ: Nucleophosmin gene mutations in acute myeloid leukemia. Arch Pathol Lab Med. 2006, 130: 1687-1692.
Cignetti A, Vallario A, Roato I, Circosta P, Strola G, Scielzo C, Allione B, Garetto L, Caligaris-Cappio F, Ghia P: The characterization of chemokine production and chemokine receptor expression reveals possible functional cross-talks in AML blasts with monocytic differentiation. Exp Hematol. 2003, 31: 495-503. 10.1016/S0301-472X(03)00066-3.
Department of Pathology, University of Maryland Medical Center, 22 S Greene Street, Baltimore, MD, USA, 21201
Borislav A Alexiev
, Wenle Wang
, Yi Ning
, William H Rodgers
, Sanford A Stass
& Xianfeng F Zhao
Department of Internal Medicine, Division Hematology Oncology, University of Maryland Medical Center, Marlene and Stewart Greenebaum Cancer Center, 22 S Greene Street, Baltimore, MD, USA, 21201
Saranya Chumsri
& Ivana Gojo
Search for Borislav A Alexiev in:
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Correspondence to Borislav A Alexiev.
BAA evaluated the H&E and immunohistochemical stains, confirmed the diagnosis, designed the report and drafted the manuscript.
YN performed the cytogenetic studies.
SC and IG provided relevant clinical information.
WHR, SAS and XFZ provided consultation.
All authors read and approved the final manuscript.
Authors' original file for figure 10
Lysozyme
Neoplastic Cell
Normal Karyotype
Myeloproliferative Disorder


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AFC North News
AFC North Roundup: The Rise and Fall Edition
In which the Ravens once again look like a championship team, the Bengals and Steelers throttle each other until one of them chokes, and the Browns deal Pat Shurmer what was probably a fatal blow.
By Rebecca Rollett Dec 28, 2012, 6:41am EST
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Charles LeClaire-USA TODAY Sport
Here are the current standings:
Baltimore Ravens: 10 - 5 (Division record 4-1)
Cincinnati Bengals: 9 - 6 (Division record 2-3)
Cleveland Browns: 5 - 10 (Division record 2-3)
Pittsburgh Steelers: 7 - 8 (Division record 2-3)
The AFC North entered last Sunday with two teams needing to win their game to keep their playoff hopes alive—the Bengals and Steelers both had a must-win game. Unfortunately they were playing each other, which meant one was bound to come up short. In the event, it was the Steelers who did so. Their defenses both played very well, but the Steelers played perhaps their best defensive game of the year, even with a decimated backfield. They held the Bengals' running backs to an unbelievable 14 yards on 16 carries, for a .9 average gain per carry. They set season highs in sacks (six) and passes defensed (nine.) But no amount of defensive awesomeness can overcome the way the offense mostly played.
Special teams looks like a goat when you look at the numbers, but the Pittsburgh kicking and gunner teams held the Bengals to two total return yards. The game featured three missed field goals between the two kickers. None of the three were really the fault of the kickers. Two of them (one by Pittsburgh's Shaun Suisham and one by Bengals kicker Josh Brown) were longer than the longest NFL field goal ever made at Heinz Field, and were straight but short, and an easy Suisham attempt was low because of a bad snap and consequently tipped.
The other two teams were playing for pride. The Browns were mathematically eliminated from any chances of making the playoffs the previous week, but have been playing pretty well as of late, and would have liked to have pulled out a win. Unfortunately, the team they faced was the Broncos, and Peyton Manning appeared to be the Peyton Manning of days of yore, zipping passes into the arms of blanketed receivers and generally doing whatever he liked. He threw for a season-high 339 yards, with three touchdowns, giving the Broncos 10 wins in a row. A Von Miller sack of Brandon Weeden sent him out of the game with a shoulder injury, and Colt McCoy finished the game. This didn't really improve things, as the offense never really got anything going. Trent Richardson, however, now has the most yards of any rookie Browns player, so that's something.
The Ravens, on the other hand, were guaranteed a playoff spot, but didn't look like a playoff team. They were even possibly fighting for the division crown, which had seemed assured a month ago. They welcomed the defending Super Bowl New York Giants into their house, and proceeded to embarrass them. All facets of the team played well, furthermore, which is always encouraging. The offense accumulated a season-high 533 yards. Special teams did their job, and the defense held Eli Manning to 150 yards and one touchdown. They now have the hat and the t-shirt, and presumably are focusing on the Lombardi. They have to get past some teams who have looked a lot better than they have most of the year, however.
Let's look at the stats:
Ben Roethlisberger is still overall the best, despite a disastrous Week 16 outing. Not that it does the 2012 Steelers much good...
Interception Watch:
This week I decided to add the number of touchdowns thrown as well for each passer—it is the second number, and the third number is TDs to INT:
Joe Flacco: 10/22 2.2
Andy Dalton: 16/26 1.625
Brandon Weeden: 17/14 .823 (Colt McCoy played part of the Week 16 game, but didn't throw a pick either.)
Ben Roethlisberger: 8/23 2.875
Pittsburgh Passers, Total: 14
It's interesting how lopsided this stat was earlier in the season. Brandon Weeden began the season with four interceptions in the first game alone, but fortunately the rate slowed drastically. His rate of touchdowns to interceptions is still pretty bad, however, being less than one touchdown for each interception. Andy Dalton did better than that, but wasn't impressive. Ben Roethlisberger has had a great year in this stat, and although his 2.875 rate doesn't match the leaders in the league this year, Aaron Rodgers, Robert Griffin III, and Tom Brady (each of whom threw at least 4 TD passes per interception,) it is just below Peyton Manning's 3+. Now if Ben can just keep from throwing a few more on Sunday...
Receivers:
Interestingly, although the number of incompletions has fluctuated a great deal during the season, the average is reasonably close as the season draws to a close. Cleveland still leads the AFC North in drops. But are those real drops? Here is the Pro Football Focus drop rate (adjusted for whether a ball was really determined to be catchable or not) for the three principal wideouts on each team:
Cincinnati, whose receivers were so good for so long, has proven to have feet of clay. The Pittsburgh receivers have been making their way back towards respectability. Anquan Boldin is the man. Enough said.
As we can see, the TEs are still more reliable, except for Jermaine Gresham. If Marvin Lewis wants my opinion (and I doubt he does) he needs to get Andy Dalton a truly reliable TE.
Rushing:
To give the Pittsburgh defense its due, check out the Bengals' rushing numbers...
NFL Ranking: (Calculated by averaging the NFL ranking for Average Yards Allowed and Average Points Allowed:)
Baltimore Ravens: No. 16 (No. 20, 361.7; No. 12 PPG, 21.4) Last week No. 22
Cincinnati Bengals: No. 7 (No. 6, YPG, 317.5; No. 8 PPG, 20.2) Last week No. 8
Cleveland Browns: No. 22 (No. 24, 373.9; No. 19, 22.9) Last week No. 18
Pittsburgh Steelers: No. 6 (No. 1, YPG, 272.9; No. 10, PPG, 20.3) Last week No. 5
Well, defense may win championships, but you have to have enough offense to get there.
Splash Plays:
Here's trending:
This is the ratio between yards gained and yards given up. Black is yards given up in each case.
This stat makes me very sad. Shaun Suisham doesn't deserve the dive his stats took this week. But that's life in a team sport, even in a position which is so likely to make one the goat sooner or later.
Point Differential:
The season, summed up in one little chart...
That's it until next week.
Mock Draft Monday: Steelers look to add a disruptive CB with top pick In the latest mock draft, the Steelers look to add another "Witherspoon" to their defensive secondary.
The quarterback salary cap conundrum Even the Steelers show how once a quarterback gets paid it is tough to keep a championship roster.
How the Steelers flipped the script for the second half of the 2022 season From 2-6 to 9-8, what really drove the turnaround.


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"Summon the bravery!" Encounters at Small Earth
Filmmaker James Murray-White describes taking part in the Small Earth conference within the stunning beauty of Snape. At this special event, psychotherapists, ecologists, economists, philosophical and spiritual thinkers gathered to address hope for future living within the ecosphere.
"Get the tools you need to understand where we're currently living: in the belly of the beast."
– Alastair McIntosh
The starting question for this powerful converging and sharing of minds in the wonderful location of Snape was "Can we return to living within the terms of Earth's ecosphere?" And this question was minutely probed and dissected over an intense, sometimes gruelling, sometimes uplifting and ultimately rejuvenating four days. The choice of location was sublime: a place I know well and often regret I don't spend enough time in — a place of water, reed beds, and the wonderful vast skies with multiple colour gradations to dream within; absolutely a setting to contemplate the miracle of our time on the blue dot of our earth.
Small Earth, big skies at Snape. Photograph: James Murray-White © 2018
A miracle indeed, but a miracle that our human species has been bent on destroying — and this convergence was aimed at therapists and psychologists with a passion to serve the planet through their work.
Here was a chance to listen, to talk and share, and also to grieve for the pain of the world.
Reclaiming what gives life
To start each day, psychotherapist James Barratt offered us all the opportunity to share into a social dreaming matrix: a space to hear and reflect upon each others' dreams. It feels particularly useful when a group has come together for a few days and is going through a process together, on any level. I found this powerful group process took us very deeply into our collective unconscious, and it was a strong learning to hear dreams and then have the chance to collectively unpick what they might be saying: finding threads and applying our experience to them.
As one of the few non-therapists attending, I dipped deeply in and needed some time to dip out. I found that it touched into lots of the work I've done since an MSc in Human Ecology at the (sadly now defunct) Centre for Human Ecology in Edinburgh some years back, and it was an honour to connect again with Gaelic shaman of the CHE and other institutions, Dr Alastair McIntosh — a keynote speaker.
McIntosh's lecture on Saturday, Reclaiming what gives life, was full of his pain and passion for the human community: quoting psalms, Shakespeare, Gaelic poets; taking us with him on his journey across the island of Harris, and into the dark heart of the world of advertising, particularly the pernicious evil of the tobacco industry.
Drawing on his comments in the film Consumed, which opened the conference, he asked of us to call back the soul, by "looking at the nature of the belly of the beast", that "the place of our calling is in the belly of the beast — don't let it take us out of our natural joy." The way forward is to "open up to that marginal realm where I suggest a healing will come."
Small earth, life abundant at Snape. Photograph: James Murray-White © 2018
A highlight of the conference was meeting with naturalist Chris Packham, who shared ways to achieve a different way of thinking about our place within the ecosphere. Ultimately, he said, if we truly tap into our human capacity for altruism, restraint and care, we might survive: "once we recognise that we are just a keystone in our own ecological microsystems."
Following on from this in a public lecture to four hundred of us, and accompanied by his dog Scratchy, Packham laid it on the line for humanity: "Summon the bravery. Look at it cold hard and in the face. It is an ecological apocalypse. We must act now."
Other notable speakers included Jungian analyst Andrew Fellows; researcher, writer and transformational coach Mick Collins; novelist Melissa Harrison; and ecopsychologist Mary-Jayne Rust.
Making the Transformocene
Andrew Fellows started by playing us a song of the Earth from a Siberian shaman: calling us into the Earth and reminding us of our belonging. Combining hard fact — that human activity is adding heat to the atmosphere at the rate of four Hiroshima explosions every second, and that two years ago the global human call for air-conditioning overtook our call for heating — with an analyst's perspective, he said: "We hang (in this ecosphere) by a thin thread, and that thread is man's psyche". Fellows spoke passionately to our failings and our human frailties — preparing us perhaps for McIntosh's attempts to lift us spiritually.
Mick Collins spoke to what he names the Transformocene: that age which transforms and changes within the recent and the new. This draws upon the very necessary shadow work that humanity must undertake, which Collins calls us "to do with depth." Naming himself a 'wounded transformer', speaking with great passion and, as described in conversations afterwards, coming from a rich discursive life of facing inner crises and awakenings, he is emerging as an important figure in our movement for change.
I relished coming back to creativity with writer Melissa Harrison, whose conviction she says comes from being part of "the last generation that was able to play and be outside." That reminded me of David Bond's 2013 documentary Project Wild Thing, which uses the diminishing statistic, from his mother's 80% spent outdoors, his own 50% outdoors playtime, to his inner-City kids' mere 3%, as the starting place to advertise the joys of being outdoors within the world. I looked after a friend's kids the night after returning from Small Earth and was shocked that they were up at 6 am, devouring screen time and off in distant virtual lands of warfare and commodity.
Melissa Harrison inspired too: "I can hold both hope and pain at the loss of species and changing climate, but it's painful. Why not try to hold hope?" She suggested that we all adopt our own home patches to protect and to closely observe, if we are not already in this act of service: "this sense of responsibility implies that we are the main players in this. Keep it cared for and vibrant."
Art, land and sky at Snape Photograph: James Murray-White © 2018
Gaining a calm presence on small Earth
Mary-Jane Rust gave an exemplary presentation that, for me, rounded off the few days and was grounded in doing, reflection and practice. With examples of eco-psychotherapy projects that re-engage folk with the earth, she spoke of "attending to our rage" at what we see and hear in terms of destruction and change and, with this, "becoming aware of our own emotional centre we gain a calm." That presence, she suggests, "delivers us the present moment, and enables an attitude of reverence, humility, and an apology — to the Earth".
These talks were followed by a range of follow-up afternoon workshops. I particularly loved the chance to forage for leaves, sticks and objects outside, and return to put them all together within an art-making workshop facilitated by Marion Green.
And I appreciated the buildings and cultural-creative environment of the Maltings, coming back to life after the end of their industrial use. The stunning beauty of Snape: the reeds, absorbing CO2, the River Alde flowing up to the buildings, and the vast East Anglian sky, all reminded me that we live in a beautiful world. It's up to each and every one of us to deeply engage, live a life in full service to the ecosphere, as well as to the human population and all other species that inhabit it too.
My thanks to the organisers, presenters, and fellow participants of Small Earth for this opportunity. May these few days enable us to continue to serve, and to quote Mick Collins, to live a life "in discipleship to nature, and to service."
The Small Earth conference took place at Snape Maltings in Suffolk, from 8th to 11th November 2018. It was organised by CONFER, an independent organisation established by psychotherapists in 1998 to provide innovative, challenging and inspiring continuing educational events for psychotherapists, psychologists and other mental health workers.
Mick Collins' idea of the Transformocene is explored in his book, The Visionary Spirit. In the Spring 2018 Issue of Permaculture magazine, Mick explained: "We're living in a time when we're standing at the threshold of the Anthropocene – an era where humans have had an impact on the Earth's eco-systems. In this way, the Anthropocene reflects the Spirit of the Times (zeitgeist), which highlights the degrading ways we've been treating the planet. In contrast, the idea for the Transformocene Age came to me after reading Carl Jung's Red Book, which chronicles his meetings with the Spirit of the Depths. Therefore, the emergence of the Transformocene is cultivated via a deeper connection to the wisdom from the collective unconscious and through our encounters with the sacred."
A writer and filmmaker linking art forms to dialogue around climate issues, whose practice stretches back to theatre-making.
A psychotherapist and writer committed to the rewilding of human nature, exploring the correlation between despoiling our natural world and the desolation of the human spirit
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Author James Murray-WhitePosted on 30th November 2018 30th December 2022 Categories ReviewTags Anthropocene, Boundaries, Care, Climate Change, Creativity, Cultural Change, Ecological Understanding, Ecology, Events, Film, Hope, Ideas, Loss, Nature, Place, Spaces, Spirituality, Workshop
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"Attending to the world's extraordinary surprise"


This page deals with rumors that are posted on a regular bases, it should be that noted that NQRS does not necessary agree or endorse in any way anything that is posted on this page, that the below are rumors put forward by the general public or found in the coarse of NQRS research. In no way is it the opinion of NQRS , we accept no responsibility for what is posted and those who wish not to have the name and contact details placed below the posted add will be respected and not released by NQRS.
During our years of research NQRS has had many claims put forward, after considerable research, some have been proven correct and other remain a myth till proved other wise. What follows is what has been put forward to NQRS over the past ten years, as well as some current day claims as well. Please do not treat them as fact, but if you can add to the claim in some way. Please feel free to add your comments.
At the end of the war, my unit placed alto of aircraft in a pit burial near strafpine , I have since been back and there is now a football oval where we put the planes. Somewhere in poor condition and others not too bad at all. All had be stripped of motors and other components.
Around the 1980's I got into a tunnel over near the Oaky air base. I got in through the creek and walked past much equipment, I have been back and the entrance is gone, but I noticed some unusually man hole covers in an area where there is no sewerage and only one was bolted down. When I went to open this, the police arrived and I was sent on my way. I seem to recall a story in the post about this bunker, on the other page was a write up about a person who found all the gold bullion around Australia, I think his name was Robinson, does any one recall this same story, I will watch the bill board for a response.


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Chamberlin Prepares to Head to Ukraine as Fulbright Scholar
CATEGORIES: Faculty & Staff, Graduate Program, Research
Dennis Chamberlin, Associate Professor
After returning from a semester of teaching Iowa State students in Urbino, Italy, Associate Professor Dennis Chamberlin is back in the U.S. for a short time before he'll have to pack his bags again for his next adventure abroad. At the end of the month Chamberlin will return to Europe, to spend the next year teaching photojournalism to graduate students as a Fulbright Scholar in Ukraine.
Chamberlin, a Pulitzer-Prize winning photographer, is one of two U.S. scholars to receive a Fulbright award to teach journalism in Ukraine. For his assignment, Chamberlin will be adding a documentary/visual journalism curriculum component to the master's program at the Ukrainian Catholic University in Lviv.
"I'm really honored by the opportunity because I know that there aren't that many opportunities for journalism professors with some of these awards," Chamberlin says.
Chamberlin's latest accolade is no small feat. The Core Fulbright Scholar Program offers nearly 500 teaching and research awards annually in over 125 countries. Last year, Iowa State had three professors who received Fulbright awards to study in Poland, Romania and Serbia.
"The Fulbright is a highly coveted award that, in many disciplines, is one of the highest honors a faculty member can receive," says Dawn Bratsch-Prince, Iowa State's senior vice president and provost. "It's an acknowledgement not only the high quality of Dennis' scholarship, but it also provides an opportunity for him to contribute to higher education on a more global scale."
Chamberlin will teach the first photojournalism course offered by the UCU, a ten-year-old institution whose journalism program will celebrate its fifth year in September. Despite being a young program, Chamberlin said that his research indicated that UCU's journalism program is among the best in the country.
"Dennis is a gifted photographer and a respected teacher, and I am confident that the Ukrainian Catholic University will find him a great resource," says Beate Schmittmann, Dean of the College of Liberal Arts and Sciences. "I also believe that Dennis will return with new inspirations and ideas and I look forward to seeing them take form."
UCU offers a two-year master's program and only enrolls 25 students in each class.
Chamberlin will spend the first semester working with second-year students and the second semester working with first-year students on photography and multimedia projects. Earlier this summer, he had a chance to meet some of the students he'll be working with when he participated in the Lviv Media Forum as an invited presenter.
"I'm most looking forward to working with the students, who are so enthusiastic and passionate about becoming journalists and doing good for society and helping forge and create a new Ukraine," Chamberlin says. "Their excitement was contagious."
After spending a few days in Lviv, Chamberlin says that he already fell in love with the city. For him, Eastern Europe has a nostalgic feel.
Chamberlin lived and worked in Poland part-time after graduating from Indiana University. His trip to Poland was his first plane ride, which became the first of many trips to the country. In 1987, Chamberlin returned and lived there for 25 years.
When he first came to Poland the country was a communist satellite state of the Soviet Union. As a young photographer, Chamberlin was among the first western journalists who were granted access to cover life inside of the communist nation in the early stages of its Solidarity movement, which eventually led to the nation's transition to a capitalist economic system and to a parliamentary democracy. After his first two-month trip to the country, he says he was "completely shocked, but in a good way," and has returned to Poland all but one year since he and his family returned to the U.S. in 2002 so he could attend graduate school.
When he was applying for his Fulbright last summer, Chamberlin said he had no hesitation about applying for a Fulbright in Ukraine, despite the nation's recent political turmoil. He says that the nation's layers of history make it a complex and interesting place that he looks forward to exploring. His experience living and working in Poland through its time of political and social change left him eager to document and help future journalists document similar changes in Ukraine.
"Chamberlin's plans for his work at the Ukranian Catholic University are a great way to extend his educational efforts to students and faculty in another country, especially a country that has been frequently in the news in recent years," says William Gutowski, Associate Dean of the College of Liberal Arts and Sciences at Iowa State.
While teaching in Ukraine for the 2016-17 school year, Chamberlin will also participate in workshop projects in rural mountain areas in Ukraine and is planning to orchestrate collaborative projects between his Ukrainian students and students at the Greenlee School. He also hopes to facilitate future study abroad programs for Iowa State students. Chamberlin's wife Joan has also secured a teaching position at UCU, where she will teach English and academic writing courses.


I like to describe myself as "an eccentric genius." People always laugh, because they think I'm joking. I always laugh, because they think I'm joking.
An astrologer once titled a reading for me, "If she's not crazy, there's no end to the good she can do you!" I laughed for a solid week, because I'd never heard myself described better.
I couldn't fit in if I tried; not authentically, anyway. I was raised specifically to be an outsider. I can blend in well enough to function, sure. But it's not my natural state of being.
Honestly, that crap gets old; by the time you get to be my age, you just want to be, y'kno? Or at least, I do. It does have a price, though. You have to tune out other people's opinions.
My neighbors do call me "the Crazy Cat Lady." I'm okay with that.
So what if I thank the spent blooms for the joy and beauty they shared when I pull them off my flowers? I'm not asking you to do it. I'm not hurting anybody. It makes me happy. I feel less guilty for plucking them off, and I do appreciate their service. I scatter them on the sidewalk, intending them to provide luck and protection to whomever crosses their paths. You may think it's nuts, but every time I send out a positive intention, it feels good. I am adding to the sum total of goodwill in the world.
Ok. I get the point. But I don't do this aloud if I see anybody outside, man. I'm semi-aware, even though I have a number of…eccentricities.
Or, I can be known as "The Crazy Cat Lady." Do what makes sense to me, without bothering with what anybody else would make of it. Do what makes me happiest, so long as it doesn't hurt anybody else.
Way I figure, it's a service. Maybe it gives them a little amusement to see what the crazy pink-haired old lady is doing. Or somebody to feel superior to. Maybe they can feel a little more normal by comparison. Who knows? The ones it bothers probably aren't a good match for my energy anyway.
I'm as kind as I know how to be; I try to add light and love wherever I go, in however humble (or eccentric) the contribution. Everything good I have to share with anybody is enhanced by living as happy as I know how to live.
I guess I'll change how much "me" I let out roam in the wild if I see a good reason; I have at times before. I try stay balanced and I do what I need to do, because I am a grown-up about what counts. But I'm really hoping I don't see good reason. It's a lot more fulfilling being authentically colorful than widely palatable.
more power to you! maybe they call you the crazy cat lady because their minds can't process beyond limited categories.
Thank you, Jeffrey. I know my "color" is very off-putting to some, whereas other people seem just lit up by it. I guess as long as I'm broadcasting it in some form, I'll attract the people most whom it speaks to positively.
I'm one of those people who are lit up – like a Christmas tree! – by it!


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Opportunities abound through the Camp and Retreat Ministries of Holston Conference for faithful Disciples to participate in this life changing work. The administration of each of the five camps will become your partner in discovering how best for you to be involved. Consider the following avenues through which God might be calling you to put your faith in action serving others through camp.
Thank you for prayerfully considering how you might become involved in these life changing ministries. Access a calender of events taking place at each campsite that might be of interest to you.


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Trump Announces Latest Round of Sanctions Targeting Iran's Supreme Leader and Senior Regime Officials
Written by Admin on June 24, 2019 . Posted in NEWS
THe president of the U.S., issued a new executive order, sanctioning the Iranian regime's supreme leader-June 24, 2019
In the latest round of sanctions, the Trump administration is targeting the Iranian regime's Supreme Leader and other senior officials.
On Monday, June 24, US President Donald Trump announced fresh sanctions against the Iranian regime following the downing of a US drone last Thursday.
Addressing Iranian Aggression
President Trump told reporters that the sanctions were a response to Iranian regime aggression but would have happened anyway due to the regime's increasing hostility in the region.
Last week, the US released a video that it claims show regime forces removing unexploded ordinance from the hull of a Japanese oil tanker in the Persian Gulf. The Trump administration believes the regime was behind two attacks on international tankers.
The sanctions will, he said, "deny the Supreme Leader and the Supreme Leader's office, and those closely affiliated with him and the office, access to key financial resources and support."
He added: "We call on the regime to abandon its nuclear ambitions, change its destructive behavior, respect the rights of its people, and return in good faith to the negotiating table."
The new sanctions are the latest moves from the Trump administration designed to limit the regime's inflow of cash. In April, Trump and his cabinet announced the designation of the regime's Revolutionary Guards (IRGC) as a foreign terror organization (FTO). The listing cut off international support for the repressive organ, limiting its ability to accept assistance, support, and counsel from international citizens or companies.
In May, Trump also reintroduced sanctions against the regime's petrochemical industry. He ordered countries to stop importing Iranian oil in an attempt to bring the regime to the negotiating table.
Tough Diplomacy
Senior figures inside the Iranian regime criticized the move. The Iranian Foreign Secretary, Javad Zarif, who was one of the names the Trump administration announced would be subject to sanctions, denounced the decision over Twitter.
In a post, he accused Trump and his advisors of despising diplomacy and having a "thirst for war." Under the new sanctions, Zarif and others will be excluded from the US financial system and their assets in the US.
The rest of the eight officials include senior figures in the Army, Navy, IRGC, and Iranian aerospace industry.
The White House also revealed that the sanctions could be extended to anybody who has business ties to the named officials. "Anybody who conducts significant transactions with these sanctioned individuals may be exposed to sanctions themselves," it said in a statement.
Welcomed by the Opposition
The Iranian opposition welcomed the announcement. President-elect of the Iranian opposition, Maryam Rajavi, called the decision "spot on" and "most impressive". She urged the US government to consider adding the Iranian Ministry of Intelligence (MOIS) to its list of foreign terrorist groups as well.
Sanctioning Khamenei & his office, the epicenter of crime, corruption & terrorism in #Iran, is spot-on & most imperative. These sanctions must be expanded to the mullahs' Ministry of Intelligence & Security (MOIS), which has blocked the uprising for a #FreeIran.
— Maryam Rajavi (@Maryam_Rajavi) June 24, 2019
The MOIS was behind a string of planned terror attacks on European soil in 2018, including a plan to detonate a car bomb at an opposition-organized event in Paris last summer.
Mohammad Mohaddessin, the chairman of the Foreign Affairs Committee of the National Council of Resistance of Iran (NCRI) also welcomed the announcement of the latest sanctions. He called the move an "imperative step."
Sanctioning Khamenei & his notorious office is the most imperative step. Thousands of mullahs, IRGC members & torturers have dominated all affairs in the country, destroyed #Iran , shackled the ppl & caused bloodshed & war. All Iranians demand the imposition of full sanctions.
— Mohammad Mohaddessin (@Mohaddessin) June 24, 2019
"Khamenei & his office are the primary center of execution, torture, suppression, the export of terrorism & warmongering," he added. "It is the source of theft, embezzlement, corruption, poverty & unemployment," and "holds the key to the nuclear weapons program."
He echoed Ms. Rajavi's calls for blacklisting the MOIS.
Tags: Iran Sanctions, Iran Terrorism, Maryam Rajavi, Mujahedin-e Khalq, National Council of Resistance of Iran (NCRI), NCRI, PMOI
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When it comes to drumming, Leah Burke is usually on beat - but real life isn't always so rhythmic. An anomaly in her friend group, she's the only child of a young, single mum, and her life is decidedly less privileged. And even though her mom knows she's bisexual, she hasn't mustered the courage to tell her friends - not even her openly gay BFF, Simon.
Serie: Simon vs. the Homo Sapiens Agenda, Titel 2
When it comes to drumming, Leah Burke is usually on beat - but real life isn't always so rhythmic. She's an anomaly in her friend group: the only child of a young, single mom, and her life is decidedly less privileged. She loves to draw but is too self-conscious to show it. And even though her mom knows she's bisexual, she hasn't mustered the courage to tell her friends - not even her openly gay BFF, Simon. So Leah really doesn't know what to do when her rock-solid friend group starts to fracture in unexpected ways. With prom and college on the horizon, tensions are running high.
I love Leah and her squad