Soft Tissue, Abdominal Wall

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 12, and subcutaneous panniculitis like T-cell lymphoma of the soft tissue of the abdominal wall. The information provided in this case was accurate and correct at the time of publication in 2021. Any changes in terminology since the time of publication may not be reflected in this case.

Microscopic sections demonstrate adipose tissue infiltrated in a lobular pattern by dense aggregates of small to intermediate-sized atypical lymphocytes with finely dispersed chromatin. Lymphocytes surround single adipocytes. In some sections, necrosis is present, but there is no angiocentricity or angiodestruction. Other sections of the overlying dermis and epidermis are uninvolved by lesional cells, and there is no epidermotropism. Occasional histiocytes are also present in the background, but no clusters of plasmacytoid dendritic cells are seen. These morphologic findings, combined with the aforementioned immunophenotype, are most consistent with subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPLTCL) is a CD8+ cytotoxic T-cell lymphoma composed of αβ T cells that involves only the subcutaneous fat and mimics a lobular panniculitis. A characteristic finding on histologic sections is rimming of adipocytes with variably sized lymphocytes in the subcutaneous fat. Necrosis is often found and can obscure other findings, making the diagnosis challenging. Epidermotropism is never identified, and angiocentricity and angionecrosis are infrequent. Its immunophenotype (βF1+, TCRγ-, CD3+, CD4-, CD8+, TIA1+, CD30-, CD56-) is consistent with an αβ T-suppressor phenotype. Proliferation markers like Ki67 can be helpful to highlight proliferating neoplastic lymphocytes (often greater than 80%, but on average ~70%) surrounding adipocytes, especially when lupus erythematosus panniculitis is in the differential (the proliferation index is essentially zero in lupus panniculitis and it will also often involve the dermis or epidermis). Molecular studies for T-cell receptor gene rearrangements demonstrate clonality but can be limited by the relatively small number of neoplastic cells present in a tissue biopsy. Some studies have identified gains of chromosomes 1pter, 2pter, 10qter, 11qter, 12qter, 16, 19, 20, and 22.

SPLTCL is rare and counts for less than 1% of all non-Hodgkin lymphomas. It has a minor female predominance over males and a large age range. While the median age of presentation is 35, pediatric patients are not uncommon, with approximately one-fifth of all cases occurring before the age of 20. It has even been rarely reported in infants. Systemic lupus erythematosus (most common) or other autoimmune diseases occur in up to one-fifth of cases. In patients with systemic lupus erythematosus, differentiating SPLTCL from lupus erythematosus panniculitis is particularly challenging. Patients with SPLTCL often present with multiple subcutaneous nodules on the trunk and extremities, usually without overlying ulceration. Clinically, the nodules are often the most apparent sign and symptom. Cytopenias and elevated liver function tests are often identified and an overt hemophagocytic lymphohistiocytosis syndrome occurs in as many as 20% of cases.

Overall, SPLTCL follows an indolent clinical course with an 80% 5-year overall survival; however, if a hemophagocytic syndrome is present it portends a poor prognosis. Combination chemotherapy has been used, but more recent studies suggest that there may be a role for immunosuppression with cyclosporine A or prednisone.

ALK-negative anaplastic large cell lymphoma (ALCL), always demonstrates CD30+ positivity. ALCL is among a heterogeneous group of hematologic malignancies that often display pleomorphic large cells or characteristic hallmark cells with abundant eosinophilic or amphophilic cytoplasm and finely clumped kidney-bean or horseshoe-shaped nuclei with a perinuclear eosinophilic region. The skin is the most common extranodal site of involvement, but it may also involve bone, soft tissue, lung, and liver.

Lupus erythematosus panniculitis (LEP) is often the most challenging differential diagnostic consideration to consider and is thought to occur on a spectrum with SPLTCL. LEP is non-clonal, and it more often demonstrates nodules of B cells, plasma cells, and aggregates of CD123+ plasmacytoid dendritic cells. Ki67 can highlight low proliferation index, even if fat rimming by lymphocytic inflammation is present, whereas the proliferation index would be elevated in SPLTCL. Additionally, LEP may involve the dermis and epidermis, which would effectively rule out SPLTCL, which is limited to the subcutaneous adipose tissue.

Mycosis fungoides (MF) tends to involve the superficial dermis and epidermis, regardless of stage. It has a T-helper immunophenotype (most commonly βF1+, CD3+, CD4+, CD8-) and often demonstrates epidermotropism. Clinically, MF exhibits a protracted clinical course versus the more aggressive cutaneous lymphomas.

Primary cutaneous gamma-delta T-cell lymphoma (PCγδTCL) does not exclusively involve the subcutaneous adipose tissue and will involve the overlying dermis and epidermis. It most often occurs in patients between the ages of 25-91 years old with a median age of 61. It is reported only rarely in pediatric patients. It is an aggressive cytotoxic γδ T- cell lymphoma that demonstrates a cytotoxic immunophenotype, with TCRγ+, βF1-, CD3+, CD4-, CD8-/+, TIA1+, CD56+, and CD57-. It can be associated with autoimmune diseases and lymphoproliferative disorders, and it often progresses to hemophagocytic lymphohistiocytosis and death within a few years. Clinically, large patches and plaques with frequent ulceration present throughout the body, most commonly on the legs or torso. Lymphadenopathy and bone marrow involvement is infrequent. Occasional cases have been found to be associated with Epstein–Barr virus infection, and rare cases have been seen in patients after TNF-alpha inhibitor treatment.

1. Bosisio F, Boi S, Caputo V, et al. Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma. Am J Surg Pathol. 2015;39(2):206-211.
2. Guitart J, Weisenburger DD, Subtil A, et al. Cutaneous [gamma][delta] t-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas. Am J Surg Pathol. 2012;36(11):1656-1665.
3. Hahtola S, Burghart E, Jeskanen L, et al. Clinicopathological characterization and genomic aberrations in subcutaneous panniculitis-like T-cell lymphoma. J Invest Dermatol. 2008;128(9):2304-2309.
4. Jaffe ES, Arbor DA, Campo E, Harris NL, Quintanilla-Martinez L. Hematopathology 2nd ed. Elsevier, Inc. 2017; Chapter 37. Lamant-Rochaix L, Fedlman AL, Delsol G and Brousset P. Anaplastic Large-Cell Lymphoma, ALK Positive and ALK Negative:Pages 673-692.
5. Jaffe ES, Arbor DA, Campo E, Harris NL, Quintanilla-Martinez L. Hematopathology 2nd ed. Elsevier, Inc. 2017; Chapter 39. LeBoit PE and Pincus LB. Mycosis Fungoides and Sezary Syndrome: Pages 713-730.
6. Jaffe ES, Arbor DA, Campo E, Harris NL, Quintanilla-Martinez L. Hematopathology 2nd ed. Elsevier, Inc. 2017; Chapter 40. Kadin ME and Kempf W. Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative disorders: Pages 731-746.
7. Jaffe ES, Arbor DA, Campo E, Harris NL, Quintanilla-Martinez L. Hematopathology 2nd ed. Elsevier, Inc. 2017; Chapter 41. Ceroni L. Primary Cutaneous T-Cell Lymphomas: Rare Subtypes: Pages 747-760.
8. Koh MJA, Sadarangani SP, Chan YC, et al. Aggressive subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis in two children (subcutaneous panniculitis-like T-cell lymphoma). Journal of the American Academy of Dermatology. 61:875-881 2009
9. LeBlanc RE, Tavallaee M, Kim YH, Kim J. Useful parameters for distinguishing subcutaneous panniculitis-like t-cell lymphoma from lupus erythematosus panniculitis. Am J Surg Pathol. 2016;40(6):745-754.
10. Magro CM, Crowson AN, Kovatich AJ, Burns F. Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia. Journal of Cutaneous Pathology. 2001;28(5):235-247.
11. WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. IARC Press; 2024 [cited 2024/6/8]. (WHO classification of tumours series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63
12. Willemze R, Jansen PM, Cerroni L, et al.: Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood. 2008;111(2):838-845.