The patient is a 72-year old woman who noted a rapidly growing soft tissue mass on her left thigh. An excisional biopsy was performed.
Histological sections reveal dense, predominantly subcutaneous infiltrate of small to medium-sized atypical
lymphoid cells of different sizes. Occasional larger lymphocytes are seen. There are many admixed histiocytes, some containing debris and focally forming multinucleated cells. There is minimal involvement of the overlying epidermis and dermis. The individual adipocyte spaces show rimming by neoplastic lymphocytes with enlarged hyperchromatic nuclei and minimal amount of cytoplasm. Foci concerning for vascular invasion are seen adjacent to large areas of necrosis. By immunohistochemistry, the atypical lymphoid cells are T-cells as highlighted by CD3 and CD5. Most of them express CD8, and over 50% of those are estimated to express cytotoxic markers Graenzyme B and TIA-1. CD4 highlights a subset of lymphoid cells and stains dimly histiocytes. Ki-67 proliferative index is approximately 40% in the lymphoid component. There are very few admixed B cells as highlighted by CD20. The atypical lymphoid cells are negative for S100, CD30 and EBV. CD68 highlights admixed histiocytes. CD138 is largely negative. T cell gene rearrangement studies detected a presence of monoclonal T cell receptor gamma gene rearrangement.
DIAGNOSIS: SUBCUTANEOUS PANNICULITIS-LIKE T-CELL LYMPHOMA
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of primary cutaneous T-cell lymphoma clinically mimicking panniculitis. According to the updated 2016 World Health Organization classification and the WHO–European Organization for Research and Treatment of Cancer (EORTC) classification of cutaneous lymphomas, SPTCL is restricted to cases with ab T-cell phenotype that express beta-F1 by immunohistochemistry. The neoplastic cells are mature cytotoxic T cells that express CD3 and CD8 and have variable loss of pan T cell antigens, starting with CD5, and followed by CD7 and CD2. They express cytotoxic markers (granzyme B, TIA-1, and perforin), CD56, CD30 and have “hotspots” of Ki-67. SPTCL is consistently negative for EBV-encoded small RNA (EBER).
The classic presentation involves multiple subcutaneous nodules and deeply seated plaques on the trunk and extremities in adults with a 2:1 female predominance. This type of cutaneous lymphoma has overall an intermediate prognosis with protracted clinical course and recurrent cutaneous relapses; the extracutaneous spread is rare. The skin nodules may ulcerate. However, mortality is much higher in patients who develop hemophagocytic syndrome, a potentially life-threatening systemic complication where the patients become severely ill with fevers, chills, malaise, weight loss, pancytopenia and hepatosplenomegaly.
Microscopically, the tumor is comprised of sheets of atypical lymphoid cells of varying sizes with hyperchromatic nuclei infiltrating diffusely throughout the subcutis, As reflected in its name, it stays confined to the subcutaneous tissue and spares the overlying epidermis and dermis. A prominent lymphoid infiltrate extends both the lobules and the septae with a characteristic “rimming” of individual adipocytes by the neoplastic cells. It is not uncommon to see admixed reactive histiocytes, especially at the sites of fat necrosis, some ingesting the lipid. There is often marked tumor necrosis and karyorrhexis with fat necrosis and admixed reactive histiocytes, some ingesting the lipid. Vascular invasion and angiodestruction can be seen, but are uncommon.
Primary cutaneous gd T-cell lymphoma (PCGDTCL) is now considered a distinct entity that is in the differential diagnosis of the SPTCL; immunosuppression appears to be play a role in its etiology. It has a highly aggressive clinical behavior. Cutaneous lesions are more likely to ulcerate and are associated with systemic symptoms in at least half of the patients. The tumor is composed of mature, activated g/d T-cells that are non-immunoreactive for beta-F1, double negative for CD4 and CD8, express CD2, CD3 and CD56.
Lupus erythematosus panniculitis is a benign histological masquerade of the SPTCL. Some of the useful histologic features of the lupus panniculitis include the presence of reactive lymphoid follicles with germinal centers, presence of plasma cells and less rampant proliferation. Ki-67 proliferative index can be helpful as the lymphocytes infiltrating around the adipocytes in lupus are mostly negative, while the “rimming” neoplastic T-cells in SPTCL are almost uniformly labeling with Ki-67. Lastly, positive EBV in situ hybridization study is most supportive of a nature killer cell, or T cell lymphoma. Also T cell gene rearrangement studies by PCT detect clonality in over 80% of cases of lymphoma, while LE does not have rearranged genes.
- L Cerroni. Lymphoproliferative lesions of the skin. J Clin Pathol. 2006 Aug; 59(8): 813–826.
- García-Herrera A, Calonje E. Cutaneous Lymphomas with Cytotoxic Phenotype. Surg Pathol Clin. 2017 Jun;10(2):409-427.
- Willemze R. Cutaneous lymphomas with a panniculitic presentation. Semin Diagn Pathol. 2017 Jan;34(1):36-43.
- Swerdlow SH, Campo E, Harris NL, Jaffe ES, et al, Eds. (2008). WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, International Agency for Research on Cancer, p. 212-213.
- Chapter 40. Primary Cutaneous T-Cell Lymphomas Rare Subtypes. In: Jaffe ES, Harris NL, Vardiman JW, Campo E, Arber DA, Eds. Hematopathology, Elsevier Saunders Publishers, St. Louis, MO, USA, 2010, p. 618-622.