T cell Lymphomas Flashcards
Extranodal NK/T cell lymphoma
Highly aggressive, poor prognosis. Most common in men of SE Asian origin. EBV-associated. Previously called “angiocentric lymphoma.” Of note, many cases previously described as “mindline lethal granuloma” are believed to be incorrectly diagnosed EN-NKTCL.
Typically presents as an ulcerating lesion in the nasal mucosa. Ulceration and pseudoepitheliomatous hyperplasia with squamous metaplasia are appreciated on histology.
Angiocentric and angioinvasive growth leading to ischemic necrosis and ulceration of the involved tissues. The tumor is composed of small, medium-sized, or large cells which are admixed with apoptotic bodies and inflammatory cells. Abundant karryorrhectic debris is present in the background, sometimes contained within tingible body macrophages. Geographic necrosis, hemorrhage, and fibrinoid exudation are common.
When present in skin, splits through fat cells and is reminiscent of subutaneous panniculitis-like T cell lymphoma.
IHC: CD2+, cCD3+, CD56+, perforin/granzyme B/TIA-1+, CD43+, CD45RO+, Fas+, Fas-L+. 15% of cases CD25+, 30% of cases CD30+. sCD3-, CD16-, CD57-. T cell markers and CD20 usually negative, but may be positive.
Genetics: TCR and Ig are not rearranged. EBV present in 90-100% of cases. p53 mutated in 25-60% of cases, correlating with large cell morphology and poor prognosis.
Subcutaneous panniculitis-like T-cell lymphoma
Enteropathy-associated T cell lymphoma
Closely linked to celiac disease and is more common in individuals of Northern European descent. However, in some patients with EATL, celiac disease is clinically silent and only diagnosed at autopsy. The cellular infiltrate is polymorphic. The neoplastic T-cells express alpha-beta T-cell receptor, but rare cases of gamma-delta do occur. Makes up 2/3 of all intestinal T cell lymphomas. Often presents as ulceration, plaque, or stricture of the small intestinal mucosa in a 50-60 year-old individual.
A small population of patients develop HLH.
Cells are moderately pleomorphic, medium-to-large size with round or angulated nuclei and prominent nucleoli. 40% of cases show large cell or anaplastic phenotype. Tumors display angiocentric and angioinvasive pattern with extensive necrosis. Inflammatory cells, including histiocytes and eosinophils, are often present. The lymphoma frequently extends to the epithelium and invades, with intraepithelial lymphocytosis.
The malignancy spreads through the mesentery, and mesenteric lymph nodes are frequently involved and show intrasinusoidal or paracortical infiltration. Sometimes lymph nodes simply show necrosis or cavitation – the results of destruction by the lymphoma.
IHC: TCRαβ+, CD3+, perforin/granzyme B+, CD103+, CD4 neg, CD5 neg, CD8 neg, CD56 neg. Those with large, anaplastic morphology are often CD30+.
Genetics: 50% display loss of heterozygosity for CDKN2A/B (p16-INK4a and p14-ARF), with resultant decrease or loss of p16/p14 expression. p53 is lost in 25% of cases, but 75% of cases display some dysregulated pattern of p53 expression. JAK3 and STAT5B are each mutated in ~25% of cases, with some JAK-STAT pathway mutation in 50% of cases. NOTCH1 amplification is also seen.
Monomorphic epitheliotrophic intestinal T-cell lymphoma
Previously called “EATCL type II”. Unlike EATCL, MEITL is not associated with Celiac’s disease, is more common in those of Asian or Hispanic descent, and is derived from TCRγδ+ T cells. There is usually no history of malabsorption.
Cells are monomorphic with medium-sized round nuclei and scant pale cytoplasm. Unlike EATL, it lacks an inflammatory component and necrosis is less prominent. Pleiomorphism is minimal or absent.
IHC: TCRγδ+, CD3+, perforin/granzyme B/TIA-1+, CD8+, CD56+, MATK+
Genetics: More commonly than EATCL, these lymphomas often have a mutation in the JAK-STAT pathway, especially in **JAK3 or STAT5B. ** Another very commonly mutated gene is SETD2. More often than not, there is myc amplification on chromosome 8q24. Less common mutations are JAK2 and GNAI2. EBV is negative.
If EBV is positive, you should double check that it is not an extranodal NK/T cell lymphoma.
Hepatosplenic T cell lymphoma
Extranodal, post-thymic T cell lymphoma that affects mostly young adults (median 35 years) with a male predominance. Classically involves liver, spleen, and bone marrow. 50% of cases have anemia and leukopenia. Immunodeficiency is an important risk factor.
Has a characteristic sinusoidal pattern of infiltration in involved organs. They are seen single-file in the sinuses of the marrow and liver. In the spleen, this gives the appearance of red pulp expansion. Cytology is that of medium-sized, monomorphic lymphoid cells with ovoid to slightly irregular nuclei. Frequently evolves into an aggressive pleomorphic lymphoma.
Since marrow involvement is so prevalent, the preferred diagnostic test is bone marrow biopsy. Marrows are typically hypercellular with trilineage hematopoiesis, but sinuses clogged with single-file or aggregated lymphoid cells. CD3 staining is recommended. A marrow specimen should also be submitted for flow cytometry.
IHC: Usually delta-gamma+, CD2+, CD3+, CD7 +/-, CD56+, CD4 neg, CD5 neg, CD8 neg, CD57 neg. TIA-1+, granzyme B neg, perforin neg.
Genetics: Frequently isochromosome 7q (50-70% of cases) and STAT5B mutations (30% of cases). STAT3 is less commonly found mutated. Trisomy 8 or loss of chromosome Y correlate with progression.
Note: delta-gamma positive in young-adult males, alpha-beta positive in adolescent females or post-menopausal females
Ddx: Hairy cell leukemia (B cell), splenic marginal zone lymphoma (B cell, also sinusoidal), aggressive NK/T cell lymphoma