Pathogenesis
MCL, like most cancers, results from the acquisition of a combination of (non-inherited) genetic mutations in somatic cells. This leads to a clonal expansion of malignant B lymphocytes. The factors that initiate the genetic alterations are typically not identifiable, and usually occur in people with no particular risk factors for lymphoma development. Because it is an acquired genetic disorder, MCL is neither communicable nor inheritable.A defining characteristic of MCL is mutation and overexpression of cyclin D1, a cell cycle gene, that contributes to the abnormal proliferation of the malignant cells. MCL cells may also be resistant to drug-induced apoptosis, making them harder to cure with chemotherapy or radiation. Cells affected by MCL proliferate in a nodular or diffuse pattern with two main cytologic variants, typical or blastic. Typical cases are small to intermediate-sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large-sized cells with finely dispersed chromatin, and are more aggressive in nature. The tumor cells accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL may also replace normal cells in the bone marrow, which impairs normal blood cell production. Diagnosis
Diagnosis generally requires stained slides of a surgically removed part of a lymph node. Other methods are also commonly used, including cytogenetics and fluorescence in situ hybridization (FISH). Polymerase chain reaction (PCR) and CER3 clonotypic primers are additional methods, but are less often used.The immunophenotype profile consists of CD5+ (in about 80% of cases), CD10-/+, and it is usually CD5+ and CD10-.
Other factors linked with dysthymia include stress, social isolation, and lack of social support.In a study using identical and fraternal twins, results indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is in part caused by heredity means. Co-occurring conditions
Dysthymia often co-occurs with other mental disorders. A "double depression" is the occurrence of episodes of major depression in addition to dysthymia. Switching between periods of dysthymic moods and periods of hypomanic moods is indicative of cyclothymia, which is a mild variant of bipolar disorder. "At least three-quarters of patients with dysthymia also have a chronic physical illness or another psychiatric disorder such as one of the anxiety disorders, cyclothymia, drug addiction, or alcoholism". Common co-occurring conditions include major depression (up to 75%), anxiety disorders (up to 50%), personality disorders (up to 40%), somatoform disorders (up to 45%) and substance use disorders (up to 50%). People with dysthymia have a higher-than-average chance of developing major depression. A 10-year follow-up study found that 95% of dysthymia patients had an episode of major depression. When an intense episode of depression occurs on top of dysthymia, the state is called "double depression." Double depression
Double depression occurs when a person experiences a major depressive episode on top of the already-existing condition of dysthymia. It is difficult to treat, as patients accept these major depressive symptoms as a natural part of their personality or as a part of their life that is outside of their control.