SPTCL is more common in women and has a predilection for younger individuals. The median age at presentation is 36 years (range 1 to 79). Approximately 50% of cases occurred in individuals 21 to 40 years of age, and 19% of cases are 20-year-old or younger patients.³ Numerous cases have now been reported in children where it represents 3.4% of all skin lymphomas.⁴

The etiology of SPTCL remains unknown. It has been reported that nearly 19% of cases of SPTCL have associated autoimmune disorders. Those included systemic lupus erythematosus, juvenile rheumatoid arthritis, Sjögren disease, type 1 diabetes mellitus, idiopathic thrombocytopenia, multiple sclerosis, Raynaud disease, and Kikuchi disease.³ A study by Yi et al.⁵ showed a series of 11 cases of SPTCL initially diagnosed as autoimmune disorders including erythema nodosum, pyoderma gangrenosum, lupus profundus, vasculitis, and inflammatory myopathy-like lesions. The authors speculated that cases with inflammatory myositis and/or Behçet disease represented paraneoplastic manifestations of SPTCL. Some of these cases (2/11) had elevation of antinuclear antibodies (ANA) in the serum, anti double stranded DNA antibody, and one case had an elevated anti neutrophil cytoplasmic antibody (ANCA). A study from the Mayo clinic on a series of 23 patients revealed preceding diagnoses of autoimmune disorders in ∼57% of cases. These included lupus panniculitis (LP), erythema nodosum, Weber–Christian disease, cellulitis, and granulomatous panniculitis of unknown etiology. The association between SPTCL and lupus erythematosus profundus (LEP) has led to the hypothesis that perhaps the two entities represent two ends of the same spectrum.^6,7 An intermediate category in between SPTCL and LEP has been proposed by Magro et al.⁸ as atypical lobular lymphocytic panniculitis. A series of five cases of SPTCL by Pincus et al.⁷ showed serologic and/or end-organ dysfunction (in addition to cutaneous changes of LEP) in all the patients. Some of the cases met 4 of 11 diagnostic criteria from the American College of Rheumatology for a diagnosis of lupus. One of the patients had pancytopenia, lymphadenopathy, and partial control of the disease with antimalarial medications. It should be noted that some cases of lobular panniculitis with a CD8⁺ phenotype can occur in children in association with clonal populations of T cells in the setting of congenital immune deficiency syndromes. Rare cases in association with HIV⁹ and sarcoidosis have also been documented.¹⁰ The association between certain medications and development of SPTCL has been described in patients receiving etanercept,¹¹ rituximab, and cyclophosphamide.¹² Unusual presentations have been reported in patients with Down syndrome,¹³ cervical cancer,¹⁴ during pregnancy,¹⁵ and neurofibromatosis type 1.¹⁶

SPTCL was originally described by Gonzalez et al.¹⁷ The typical lesions consist of nodules/tumors or skin plaques, which can vary in diameter from 1 to 20 cm or more (Fig. 15-1). Lesions are frequently multifocal (78%) and rarely ulcerate (6%). They mostly present on the extremities and less frequently on the trunk and face. Facial lesions might be associated with extraocular muscle palsy.¹⁸ They can clinically simulate other causes of panniculitis, such as erythema nodosum¹⁹ or LP. Other rare clinical presentations might mimic dermatomyositis,^20,21 morphea,²² cellulitis,²³ facial edema,²⁴ venous stasis–like ulceration,²⁵ lipomembranous panniculitis,²⁶ eschar-like crusting,²⁷ erythromelalgia,²⁸ and alopecia.²⁹ Rare cases in the breast have been reported.^30,31 Lipoatrophy might be seen after resolution.³²

Systemic symptoms occur in 40% to 50% of cases and include fever, chills, night sweats, and weight loss. Cytopenias and alterations in liver enzymes often occur. Hemophagocytic syndrome (HPS) is seen in 17% of cases and is associated with high mortality (46% at 5 years).³ HPS is more prevalent in SPTCLs with γδ phenotype (45%).^33,34 Less common clinical manifestations include lymphadenopathy, hepatosplenomegaly, pleural effusions, and bone marrow involvement.^35,36 However, in most cases of SPTCL without HPS the systemic workup is usually negative for extracutaneous disease.^37,38 Transmission of the disease has been documented after allogeneic bone marrow transplantation¹¹ and cardiac transplantation.³⁹ Some cases show spontaneous resolution.^40,41,42

The prognosis of SPTCL is excellent with a 5-year overall survival of >80%.³³ Approximately 60% of patients achieve complete remission, and about 12% die of the disease. Most of the mortality is due to HPS, which usually develops late in the course.³ Pediatric cases appear to have higher recurrence rates (>50%), but overall low mortality.⁴³ A fatal case with overlap features of lupus and hemophagocytosis had been reported.⁴⁴

There is a dense, adipotropic lymphoid infiltrate within subcutaneous lobules mimicking a lobular panniculitis.^{3,34,43,63,64,65,66,67,68,69,70} Septal involvement is mild or absent (Figs. 15-2, 15-3, 15-4 and 15-5). Extension of the infiltrate into the deep reticular dermis, surrounding and occasionally infiltrating sweat glands, hair follicles, and sebaceous glands can be seen.⁷¹ Infiltration of the superficial epidermis and/or dermis is exceedingly rare and, if present, should raise the diagnostic consideration of mycosis fungoides (MF) with a secondary panniculitic presentation or GDTCL. Rimming of neoplastic cells around adipocytes is characteristic but not pathognomonic. Similar findings can be seen in LP and in association with other lymphoproliferative disorders such as tumor-stage MF, aggressive epidermotropic CD8⁺ T-cell lymphoma, extranodal NK/T-cell lymphoma, GDTCL, blastic plasmacytoid dendritic cell neoplasm, secondary diffuse large B-cell lymphoma, and leukemia cutis.⁷² Intravascular thrombi adjacent to tissue necrosis are not uncommon, whereas angiotropism and angiodestruction are exceedingly rare. Necrosis and karyorrhexis along with nonneoplastic inflammatory infiltrates (histiocytes, small lymphocytes, and neutrophils) are often prominent, and may mask the underlying neoplastic process. In such scenarios, the presence of necrotic malignant lymphocytes (ghost cells) could be useful in identifying the atypical population. Later stages might show epithelioid histiocytes, granulomas, or lipomembranous changes.²⁶ Eosinophils and plasma cells are uncommon; however, the presence of plasma cells should raise the differential diagnosis of LEP or LEP/SPTCL overlap.^{6,73,74,75,76,77,78,79,80} In the presence of intralobular histiocytes with phagocytosed red blood cells or apoptotic elements, workup for HPS should be considered.⁸¹