Follicular Helper T cell Lymphoma

The findings are diagnostic of a non-epidermotropic CD4+ T cell lymphoma. Overall the architectural growth pattern, cytomorphology and phenotypic profile is compatible with unilesional (i.e. as opposed to the more common multicentric form) primary cutaneous follicular helper T cell lymphoma of which there are two main types as will be alluded to presently. This non-epidermotropic nodular architectural disposition arranged around vessels and adnexal structures defines the basic architecture encountered in multifocal and unilesional primary cutaneous follicular helper T cell lymphoma. The designation as being a follicular helper T cell lymphoma relates to the extensive staining for PD1 as well as nuclear staining for NFAT amidst the neoplastic cells. In addition it is characteristic to see a significant degree of dendritic cell hyperplasia, The fact that there are a number of large atypical cells that exceed 30% of the infiltrate is important in regards to the specific categorization. If it was a more diffuse pattern of growth then this particular lymphoma would be considered a relatively aggressive one falling under the designation of peripheral T cell lymphoma, not otherwise specified. However when the neoplasm does maintain this distinct nodular growth pattern with a background of many small and intermediate sized lymphocytes my experience has been that these cases of primary cutaneous follicular helper T cell lymphoma still follow a very indolent course when presenting as a solitary lesion.

The patient does present with a solitary lesion. He is otherwise healthy. The two main forms of primary cutaneous follicular helper T cell lymphoma exhibiting this unilesional presentation with this particular nodular architecture showing a significant neoplastic large cell populace would be in the context of 1: CD30 + primary cutaneous pleomorphic small/medium sized T cell lymphoma which is a unilesional form of follicular helper T cell lymphoma versus 2: CD30 - primary cutaneous follicular helper T cell lymphoma not otherwise specified.

In this case I would use the designation of primary cutaneous follicular helper T cell lymphoma unilesional variant if the large atypical cells were CD30 negative. However in this case the large atypical cells express CD30. We are in the process of reporting cases of unilesional primary cutaneous pleomorphic small/medium sized T cell lymphoma that have many large atypical CD30 positive T cells that exceed the 30% large cell cutoff that defines the conventional number of large cells allowed in this neoplasm. Perhaps in the future one might completely abandon the term of primary cutaneous CD4+ small/medium sized pleomorphic T cell lymphoma since it is a form of follicular helper T cell lymphoma and simply refer to these cases as unilesional follicular helper T cell lymphoma where both the CD30 negative and CD30 positive variants appear prognostically similar.

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Slide 1: 63 year-old man with a single lesion of the posterior leg. The biopsy shows a superficial and deep nodular lymphocytic infiltrate.

Slide 2: The infiltrate is arranged around blood vessels and adnexal structures. There is a narrow grenz zone that separates the infiltrate from the overlying epidermis. There is also some permeation of the interstitium by this infiltrate. The infiltrate is not significantly epidermotropic.

Slide 3: The infiltrate has a heterogeneous composition comprising small, intermediate and larger lymphoid forms. The cells are atypical albeit non-cerebriform in their appearance. They have angulated and irregular nuclear contours with marked nuclear hyperchromasia. The larger atypical cells are in the 20-30 micron size range. These larger cells are quite pleomorphic. They are mononuclear in nature but do vary in terms of their nuclear shapes. They do not really have an immunoblastic morphology given the hyperchromatic closely condensed nature of the chromatin.

Slide 4: The infiltrate has a heterogeneous composition comprising small, intermediate and larger lymphoid forms. The cells are atypical albeit non-cerebriform in their appearance. They have angulated and irregular nuclear contours with marked nuclear hyperchromasia. The larger atypical cells are in the 20-30 micron size range. These larger cells are quite pleomorphic. They are mononuclear in nature but do vary in terms of their nuclear shapes. They do not really have an immunoblastic morphology given the hyperchromatic closely condensed nature of the chromatin. There were a number of atypical mitotic figures. The percent of these larger atypical cells borders on 30-40%. There are a few admixed histiocytes and scattered eosinophils. The infiltrate is vasocentric, perifollicular and also shows accentuation around the straight eccrine duct. There is some evidence of vascular injury characterized by endothelial cell swelling and red cell extravasation. There is also minimal intraluminal fibrin deposition. There is a significant degree of histiocytic infiltration albeit it is obscured by the neoplastic lymphoid populace but does impart some vague granulomatous features to this infiltrate.

Slide 5: There is extensive highlighting of the infiltrate for the pan T cell marker CD3.

Slide 6: CD4 stain. The CD4 to CD8 ratio is markedly elevated and is in excess of 10:1 clearly indicative of CD4+ T cell lymphoproliferative disease.

Slide 7: There is extensive highlighting of the infiltrate for the pan T cell marker CD5

Slide 8: There is extensive highlighting of the infiltrate for the pan T cell marker CD7 which is diminished compared to CD3 and CD5.

Slide 9: This is the CD8 stain. The CD4 to CD8 ratio is markedly elevated and is in excess of 10:1 clearly indicative of CD4+ T cell lymphoproliferative disease.

Slide 10: CD20 immunostain. There is a minor B cell component most conspicuous around the hair follicles. Roughly 20% of the infiltrate is in the context of B cells. These B cells do not form germinal centers but rather are disposed primarily in a single cell fashion..

Slide 11: The larger cells which occupy roughly 30-40% of the infiltrate exhibit CD30 positivity.

Slide 12: There is extensive immunoreactivity in the cytoplasm for NFAT. However there are also many cells that show nuclear staining for NFAT. In any one high power field there are over 100 cells that show nuclear staining for NFAT.

Slide 13: There is an extensive degree of staining for PD1. The PD1 preparation highlights the larger cells but also the small and intermediate size lymphocytes. Likely 60% of the infiltrate is PD1 positive. The findings are diagnostic of a CD30+ PRIMARY CUTANEOUS CD4+ SMALL/MEDIUM SIZED PLEOMORPHIC T-CELL LYMPHOMA AS A DISTINCT SUBSET OF UNILESIONAL FOLLICULAR HELPER T CELL LYMPHOMA