A 75-year-old man presented with recurrent pruritic eczema of the penis and scrotum that was refractory to medication of the local dermatologic clinic for one and a half years. The lesion consisted of an erythematous and indurated plaque with ulceration and exudation (). Review of the patient's history revealed that he underwent right hemicolectomy for adenocarcinoma in the ascending colon when he was 62 years old. He remained under regular follow-up for 13 years, during which no metastases were reported. Examination of skin biopsy from the inguinal folds revealed large cells with clear to eosinophilic cytoplasm that had infiltrated into the epidermis, singly and in clusters (). The initial histologic diagnosis of the skin biopsy was EMPD. The preoperative instrumental investigations showed no evidence of recurrence on the previous surgical site or other underlying internal malignancy. The patient underwent a mapping biopsy at multiple sites to accurately establish the boundary of the lesion, followed by wide excision and closure of the defect with a skin graft.\nThe resected perineum and penile shaft showed ill-defined indurated nodules with a firm consistency. The lesion in the overlying epidermis measured 6 cm, with a 1.5-cm-sized mass in the dermis. The cut surface was solid and gray-white with focal mucinous appearance. On histologic examination, the lowpower view showed a relatively well-defined mass occupying the dermis and subcutis (). The overlying epidermis showed irregular epidermal hyperplasia containing scattered large cells arranged singly or in groups, as in the previous skin biopsy, suggesting an epidermal pagetoid spread of underlying tumor cells (). The tumor showed two composite features in which solid nests of poorly differentiated carcinoma were juxtaposed with paucicellular mucinous lakes with floating tumor cell clusters (). The latter accounted for the majority of the tumor, about 70%, and the rest consisted of poorly differentiated components. Tumor cells in both the mucinous pool and more cellular area revealed the same histological features of abundant eosinophilic cytoplasm and large vesicular nuclei with frequent mitoses up to 7/10 high power field (, ). In situ lesions similar to ductal carcinoma in situ of the breast were also observed () with colonization of the hair follicles (). Overall histology suggested a mucinous carcinoma with minor poorly differentiated components.\nHistological differential diagnosis included PCMC and late metastasis of the previously diagnosed colon cancer. Histologic review of the patient’s previous colon cancer showed a 4.3-cm moderately differentiated adenocarcinoma with the assigned stage of T3N0M0. The tumor consisted of well-formed or cribriform patterns of tumor glands with frequently observed dirty necrosis (). There was no mucin production observed in the skin lesion.\nImmunohistochemical studies were performed. The Paget’s and dermal tumor cells of the skin lesion were positive for cytokeratin (CK) 7, CK20, gross cystic disease fluid protein-15 (GCDFP-15) (–), and carcinoembryonic antigen (CEA), but negative for caudal-related homeobox gene 2 (CDX-2). On the other hand, tumor cells of the colon cancer were positive for CK20, CDX-2, CEA, but not gross cystic disease fluid protein 15 or CK7. Additional staining of human epidermal growth factor receptor 2 and estrogen receptor (ER) was observed in the skin lesion (, ), but the lesion was negative for progesterone receptor (PR). Myoepithelial cells surrounding the carcinoma in situ were highlighted by CK5/6 immunostaining (). The overall immunohistochemical findings of the skin lesion were different from those of colon cancer but similar to those of breast cancer, but similar to those of breast cancer, indicating sweat gland origin. On the basis of these histologic and immunohistochemical findings, the two malignancies were considered to differ in origin, and the present case was a primary mucinous carcinoma of the skin.\nAnother challenge was to determine whether the minor poorly differentiated components were eccrine or apocrine in origin because there was no clear distinction in histologic and immunohistochemical features. We concluded apocrine differentiation of the lesion due to the location in the groin, where apocrine glands are many in number, and to the resemblance of apocrine carcinoma in the breast even though decapitation secretion was absent. In addition, close approximation and colonization of the hair follicle () favored the origin of the follicularapocrine unit.\nThe final pathologic diagnosis was PCMC with EMPD showing apocrine differentiation.\nThis case was approved by the institutional review board (IRB) of Kosin University Gospel Hospital, and informed consent was waived by the IRB (IRB reference number: 2017-10-010).
Our case highlights a 73-year-old male who was referred for surgical correction of right eye ptosis that was present for 2 years. He complained that his ptosis was progressively worsening. On assessment of his driver’s license from 5 years prior, the right sided ptosis was present. His past medical history was significant for diabetes mellitus, dyslipidemia and remote head trauma resulting in a basal skull fracture. His past ocular history was significant for prior cataract extraction and primary open angle glaucoma which was controlled medically.\nOn initial examination, his visual acuity was 20/25–1 and 20/20–1 in the right and left eye, respectively. His intraocular pressures were 12 mmHg bilaterally. His anterior segment examination was unremarkable. His posterior examination was unremarkable apart from glaucomatous disc damage. His ocular movements were full and there was no enophthalmos or exophthalmos. He was noted to have right-sided ptosis (Fig. ). Upon palpation of his right orbit, he was noted to have an upper lateral orbital rim mass. The patient was otherwise asymptomatic; he did not report pain, pressure or right-sided visual deficits. Computed tomography (CT) noted ill-defined soft tissue thickening anterior to the right globe, predominantly pre-septal but with slight post-septal extension (Fig. ).\nAn orbitotomy was performed for biopsy of the right orbicularis muscle and anterior orbit through an eyelid crease incision. The pathology revealed diffusely and deeply infiltrating tumour cells extending through the dermis, subcutis, orbicularis muscle bundles and nerve fibers (Fig. a-c); the tumour cells were noted to have a monotonous histiocytoid appearance with foamy granular eosinophilic cytoplasm (Fig. d). There was diffuse infiltration of the dermis with sparing of the epidermis and lack of surrounding desmoplastic reaction. In specific areas, lesional cells showed single filing. Sebaceous differentiation was not seen, and the epidermis did not show a cutaneous Paget’s disease-like change. At high magnification, intracytoplasmic vacuoles and occasional intermixed signet ring cells were identified (Fig. e). They were characterized by a crescent-like nuclei and a main, centrally located cytoplasmic vacuole. Rare scattered mitoses were noted. Immunohistochemical staining revealed the tumour cells to be AE1/AE3, CK7, GCDFP-15, E-cadherin, androgen receptor (AR) stain and GATA3 positive (Fig. f). No appreciable staining was noted with CK20, CDX2, TTF-1, S100, mammaglobin, p63, uroplakin-II, PSAP, PAX8, tryptase, CD20, CD117, CD43, WT1, calretinin and PSA stains. MIB-1 showed a low proliferative index (about 10%). Progesterone receptor stain was negative; however, estrogen receptor stain did show patchy staining (about 15–20%). Final pathology report confirmed the diagnosis of primary cutaneous signet-ring cell/histiocytoid carcinoma of the right eyelid. Systemic workup was performed with positron emission tomography (PET) and full body CT which failed to identify a distant primary malignancy or metastatic disease.\nThe decision was made to attempt surgical excision of the tumor. After the bulk of the grossly apparent tumor was removed, intraoperative frozen sections were sent. Unfortunately, frozen pathology was unable to differentiate tumor cells from normal inflammatory histiocytes. Thus, numerous superficial biopsies of the right periorbital soft tissue were performed, which revealed extension significantly further than the gross disease. Thereafter, the patient underwent a wide orbital exenteration with reconstruction using a temporary split-thickness skin graft. On final permanent sections, there still remained positive margins.\nLater, the patient underwent further resection by the head and neck oncology team, in which further extensive resections were performed around the original rim of the exenteration site. The previous skin graft was resected, the orbital apex was further dissected, the maxillary sinus was removed and further resection into the skull base was performed. Neck dissection was performed in preparation for free muscle-skin flap reconstruction after all skin and deep margins were found to be negative.\nTwo rounds of adjuvant post-operative radiation were administered (5040 cGy in 28 fractions) 3 months after his reconstruction. Post-radiation PET and CT scans were negative for recurrence 6 months after his initial surgery. There was no evidence of recurrence after 4 years of follow-up.