How do I differentiate lupus panniculitis from a primary subcutaneous T‑cell lymphoma, and what are the recommended diagnostic work‑up and treatment options?

Differentiating Lupus Panniculitis from Subcutaneous Panniculitis-Like T-Cell Lymphoma

The most critical diagnostic distinction relies on identifying Ki-67 hotspots enriched with atypical CD8+ T-cells rimming adipocytes (specific for SPTCL), versus the presence of plasmacytoid dendritic cell clusters, lymphoid follicles with germinal centers, and prominent plasma cells (specific for lupus panniculitis). 1

Diagnostic Work-Up Algorithm

Step 1: Initial Histopathologic Assessment

Examine for features that strongly favor lupus panniculitis:

• Lymphoid follicles with reactive germinal centers (present in 45% of lupus panniculitis, absent in SPTCL) 2
• Clusters of plasmacytoid dendritic cells (PDCs) identified by CD123 staining (present in 81% of lupus panniculitis vs only 18% of SPTCL) 3
• Prominent plasma cell infiltrates admixed with lymphocytes (91% of lupus panniculitis cases) 2
• Hyaline/lipomembranous fat necrosis pattern (characteristic of lupus panniculitis) 3
• Dermal mucin deposition (73% of lupus panniculitis cases) 2
• Epidermal interface changes with hyperkeratosis and follicular plugging 4

Examine for features that strongly favor SPTCL:

• Fibrinoid/coagulative fat necrosis pattern (characteristic of SPTCL) 3
• Moderate to marked nuclear atypia in lymphocytes 3
• Adipocyte rimming by atypical lymphocytes 3, 1

Step 2: Immunohistochemistry Panel (Essential)

Apply this limited but highly specific panel:

• Ki-67, CD3, CD4, and CD8 immunostains to identify diagnostic "Ki-67 hotspots" 1

Ki-67 hotspots are pathognomonic for SPTCL:

• Foci showing high Ki-67 proliferation enriched with atypical CD8+ cytotoxic T-cells rimming adipocytes are highly specific for SPTCL and not identified in lupus panniculitis 1
• The combination of lymphocyte atypia plus adipocyte rimming by CD8+ T-cells within Ki-67 hotspots is diagnostic of SPTCL 1

Additional immunophenotyping findings:

• SPTCL shows α/β T-cell phenotype (critical for diagnosis, as γ/δ cases are now classified separately) 5
• Loss of CD5 expression with or without diminished CD7 favors SPTCL 4
• CD8 dominance in the subcutaneous infiltrate favors SPTCL 4
• B-cell aggregates arranged at periphery of fat lobules favor lupus panniculitis 2, 6

Step 3: Molecular Analysis

Perform T-cell receptor (TCR) gene rearrangement studies:

• Polyclonal TCR-gamma gene rearrangement (polyclonal smear) supports lupus panniculitis 2
• Monoclonal T-cell clone supports SPTCL, though high-throughput sequencing may be needed to confirm neoplastic clones in evolving disease 1

Step 4: Clinical Correlation (Critical for Final Diagnosis)

Assess for clinical features of SPTCL:

• Hemophagocytic syndrome (HPS) is the most critical prognostic indicator—present in SPTCL patients with dramatically worse outcomes (5-year survival 46% with HPS vs 91% without HPS) 5
• Fever and cytopenias requiring immediate intervention 5
• Age >50 years (median age 55 years for SPTCL vs 38-40 years for lupus panniculitis) 4
• Lack of response to hydroxychloroquine/steroids and progressive disease 4

Assess for clinical features of lupus panniculitis:

• Prior or concurrent diagnosis of systemic lupus erythematosus 4
• Female predominance 2
• Response to hydroxychloroquine and/or corticosteroids with recurrence after cessation 4
• Overlying skin changes characteristic of lupus erythematosus 4

Critical Diagnostic Pitfalls

Beware of histologic overlap cases:

• Some cases show features of both SPTCL and lupus panniculitis in different areas of the same biopsy, raising the possibility of a disease spectrum 6
• Hyaline lipomembranous change, B-cell aggregates, PDC clusters, and plasma cells can occasionally be seen in SPTCL (including patients with HPS), so these features favor but do not absolutely exclude SPTCL 1
• Erythrophagocytosis in lupus panniculitis indicates supervening subcuticular lymphoid dyscrasia and warrants closer monitoring 4
• Cases of lupus panniculitis with phenotypic abnormalities (CD5/CD7 loss, CD8 dominance) or T-cell clonality may show local destruction, fever, and cytopenias but still respond to hydroxychloroquine/prednisone 4

When the diagnosis remains indeterminate:

• Consider the category of "indeterminate lymphocytic lobular panniculitis (ILLP)" for cases without prior lupus history, no systemic symptoms, and clinical course not suggestive of lymphoma 4
• These patients respond to hydroxychloroquine/steroid therapy with recurrences following cessation, similar to lupus panniculitis 4

Treatment Recommendations

For Confirmed SPTCL

Without hemophagocytic syndrome:

• Systemic corticosteroids or other immunosuppressive agents should be considered first-line 5
• For solitary or localized lesions, radiotherapy with electrons is advised 5
• Prognosis is excellent with 5-year overall survival of 91% 5

With hemophagocytic syndrome:

• Multi-agent chemotherapy is required immediately due to extremely aggressive clinical syndrome 5
• Prognosis is significantly worse with 5-year overall survival of only 46% 5

For Confirmed Lupus Panniculitis

First-line therapy:

• Hydroxychloroquine and/or systemic corticosteroids 4
• Expect recurrences following cessation of therapy, requiring maintenance treatment 4
• Prognosis is excellent with no mortality in well-characterized cohorts 1