When panniculitis becomes lymphoma: Timely diagnosis and treatment of a subcutaneous panniculitis-like T-cell lymphoma hiding in plain sight

INTRODUCTION

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic cutaneous T-cell lymphoma that is typically localized to the subcutaneous adipose tissue and presents with associated constitutional symptoms. Here, we report a case of SPTCL with occasional systemic dissemination, emphasizing the clinicopathological features, thereby bringing familiarity to the diagnosis of this rare entity.

CASE REPORT

A previously healthy 21-year-old female, working as an attendant at an Ayurvedic spa, presented with an 8-month history of progressively enlarging, painful, erythematous, lichenified, and leathery skin plaques involving both limbs and the abdomen. This was accompanied by B symptoms, including weight loss, drenching night sweats, and fatigue. Prior consultations had resulted in diagnoses of eczema, psoriasis, cellulitis, a suspected arthropod bite, and even a raised question of abuse. There was no response to topical steroids or antibiotics.

Clinical examination revealed multiple indurated, erythematous-to-violaceous lesions with peripheral scaling and no significant organomegaly [Figure 1]. Initial laboratory investigations showed mild anemia, markedly elevated lactate dehydrogenase (lactate dehydrogenase [LDH] 1,336 U/L; normal 140–280), alkaline phosphatase (320 U/L), and ferritin (>2000 ng/mL). Peripheral blood smear showed no atypical lymphocytes. Pancreatic enzyme levels were within normal limits (58 U/L). Systemic lupus erythematous was ruled out following a negative antinuclear antibody (ANA) profile.

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Figure 1:

(a and b) The patient presented with multiple, indurated, erythematous to violaceous lesions. (c) The lesions have resolved after six cycles of chemotherapy.

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Histopathological examination of multiple punch biopsies demonstrated a dense lymphoid infiltrate extending from the reticular dermis into the subcutaneous fat, with characteristic “rimming” of individual adipocytes by atypical lymphocytes [Figure 2a]. The neoplastic cells exhibited irregular, hyperchromatic nuclei with conspicuous nucleoli. The background showed prominent karyorrhexis, fat necrosis, and “bean-bag” histiocytes containing cellular debris, morphology indicative of a subcutaneous lymphoproliferative disorder with panniculitis [Figure 2b].

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Figure 2:

(a) Microscopy shows an atypical lymphocytic infiltrate extending from reticular dermis to subcutaneous fat (hematoxylin and eosin [H&E] staining, ×4 power). (b) Bean bag histiocytes , as highlighted by the red arrows, are seen in the background, which are typical of this disease (H&E staining, ×40 power). (c) Atypical lymphocytes, as highlighted by the red arrows, are seen rimming the adipocytes, showing strong membranous and cytoplasmic positivity for CD3 (immunohistochemical staining for CD3, ×40 power).

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Immunohistochemistry revealed the neoplastic cells to be strongly positive for CD3 [Figure 2c], CD8, CD7, and granzyme B, with partial loss of CD5. The KI-67 proliferation index was markedly elevated at 75%. Importantly, stains for CD4, CD20, CD30 and CD56 were negative. This assisted in effectively excluding other differentials such as gamma-delta T-cell lymphoma or natural killer (NK)/T-cell neoplasms, further supported by the lack of involvement of dermis and deeper tissues, absence of angioinvasion, and minimal areas of necrosis.

Staging positron emission tomography-computed tomography (PET-CT) revealed unexpected multifocal hypermetabolic lesions in the liver, distal femora, tibiae, and tarsal bones. Bone marrow biopsy showed florid megakaryocytic hyperplasia and a focal increase in interstitial lymphoid cells, confirming stage IV disease according to the American Joint Committee on Cancer/Union for International Cancer Control staging criteria for non-Hodgkin’s lymphoma. Occasional hemophagocytic histiocytes were noted, though not meeting full criteria for hemophagocytic lymphohistiocytosis (HLH) as per the Histiocyte Society guidelines (absence of splenomegaly, normal triglycerides, and soluble CD25 levels).

The patient was initiated on CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) with a dramatic response. After six cycles, there was complete resolution of skin lesions and normalization of LDH. Follow-up PET-CT showed complete metabolic response with resolution of previously noted osseous and hepatic lesions. The patient, who had been wheelchair-bound at presentation due to pain and weakness, regained full mobility and returned to work [Figure 1].

DISCUSSION

SPTCL represents <1% of all non-Hodgkin’s lymphomas and usually follows an indolent course limited to subcutaneous tissue. The major histopathological differentials considered include the panniculitis group (lupus panniculitis and pancreatic panniculitis) and aggressive lymphomas, namely gamma-delta T-cell lymphoma and extranodal NK/T-cell lymphoma. Negativity for antinuclear antibody (ANA) test and specific histologic feaatures (lack of B lineage cells and plasma cells with mucin) excluded lupus panniculitis, while pancreatic panniculitis was ruled out by normal pancreatic amylase levels, lack of saponification, and absence of neutrophils. The classic immunohistochemistry and histology omitted aggressive lymphomas [Table 1].^[1]

The 2022 World Health Organization classification also emphasizes that SPTCL can be distinguished from aggressive gamma-delta T-cell lymphomas through CD56/T-cell receptor-gamma negativity, and from extranodal NK/T-cell lymphoma by its Epstein–Barr virus-encoded RNA negativity.^[1] Hepatitis A virus cellular receptor 2 mutations have been identified in HLH-associated cases, though testing was not available here.^[2] Prognosis remains favorable (5-year survival 85–91%) with chemotherapy, contrasting sharply with gamma-delta variants (10% survival).^[3]

Our case is remarkable for several reasons:

1. The extensive systemic involvement (bone and liver) seen here occurs in <5% of cases^[4]

2. Given the histological resemblance to the benign panniculitides, this case exemplifies the diagnostic complexities of SPTCL^[5]

3. The presence of marrow hemophagocytosis without meeting full HLH criteria illustrates the variable clinical spectrum of this association.

CONCLUSION

This case highlights the importance of including SPTCL in the differential diagnoses of treatment-resistant panniculitis-like lesions with constitutional symptoms, where PET-CT provides valuable assistance in uncovering extracutaneous involvement. CD8+/Granzyme B+ expression, high Ki-67, and negative lupus markers excluded lupus panniculitis despite histological overlap. The pathognomonic CD8+/CD56-immunophenotype serves as a critical diagnostic feature to distinguish SPTCL from histologic mimics, particularly aggressive gamma-delta T-cell lymphomas. Importantly, our experience reaffirms that CHOP chemotherapy retains therapeutic efficacy even in advanced disease with multisystem dissemination, offering favorable outcomes when initiated promptly following accurate immunohistochemical characterization.