Lymphoma & related disorders

• Primary cutaneous cytotoxic T cell lymphoma, which typically involves subcutaneous adipose tissue (Am J Surg Pathol 1991;15:17, JAMA Dermatol 2022;158:1167, Asia Pac J Clin Oncol 2023;19:27, Leuk Lymphoma 2021;62:2130, J Am Acad Dermatol 2021;85:1093, Blood 2020;135:1058, Blood Adv 2021;5:3919)
  • First described by Gonzalez and colleagues in 1991
  • Defined as a distinct entity by the 2001 World Health Organization Classification of Hematopoietic and Lymphoid Tumors
    • Initially included cases of both α / β and γ / δ phenotypes

Contributed by Roberto N. Miranda, M.D.

Contributed by Roberto N. Miranda, M.D.

• Skin involvement (JAMA Dermatol 2022;158:1167, Surg Pathol Clin 2021;14:177, Histopathology 2013;62:1057, Blood Adv 2021;5:3919, J Clin Pathol 2015;68:954)
  • Epidermis and dermis are usually spared
    • Interface dermatitis, plasma cell aggregates, follicular plugging or mucin deposits may occur
    • Minimal involvement by lymphoma cells of deep dermis can be observed
  • Lobular infiltrate
    • Variable size (small to intermediate) lymphocytes with hyperchromatic and irregular nuclei and scant pale / clear cytoplasm
      • Subset of cases with large cell or pleomorphic morphology
    • Variable density of atypical lymphocytes involving lobules and sparing septa
      • Rimming adipocytes or lipid vacuoles
    • Background
      • Scattered reactive plasma cells and neutrophils
      • Absence of plasmacytoid dendritic cells aggregates (> 10 cells)
      • Reactive histiocytes, sometimes dense and forming granulomas or lipogranulomas
  • Necrosis may vary from mild to extensive
  • Karyorrhexis, mitotic figures and hemorrhage can be present
  • Hemophagocytosis may be detected in skin or other tissues (e.g., bone marrow)
• Bone marrow is not involved by overt lymphoma cells but aggregates of small lymphocytes can be detected around adipocytes

Contributed by Roberto N. Miranda, M.D.

• Lupus erythematosus panniculitis (Am J Dermatopathol 2010;32:24, Asia Pac J Clin Oncol 2023;19:27, Histopathology 2013;62:1057, Am J Surg Pathol 2016;40:745):
  • F > M
  • Multiple or single lipoatrophy, erythema or subcutaneous nodules
  • Extremities (upper arms) > face > trunk
  • Epidermal and dermal changes
    • Lymphocytic lobular / septal panniculitis with mild or no cytological atypia
    • Intradermal mucin, hyaline lipomembranous changes, mild vasculitis, reactive germinal centers and plasma cells
    • Aggregates of CD123+ plasmacytoid dendritic cells
  • Absence of atypical T cells
    • Mixed cell infiltrate: CD3+, CD4+, CD8+, CD20+
  • Low Ki67 proliferation index (~< 10%)
  • Usually polyclonal TCRγ gene rearrangement
    • Rare cases with monoclonal peak
• Cytophagic histiocytic panniculitis (Ital J Pediatr 2014;40:17):
  • Infiltration of subcutaneous by T cells and phagocytic histiocytes
  • Isolated in skin or associated with other malignancies
    • Skin lesions may remain
  • No evidence of monoclonal rearrangements of TRB or TRG gene
• Cold panniculitis (J Clin Pathol 2015;68:954):
  • Physical panniculitis
  • Appropriate clinical history
  • More common in pediatric patients
    • Face (chin and cheeks)
      • Different chemical composition of the adipose tissue
  • Adults: usually after chronic use of ice pack or environmental exposure
  • Lymphoid infiltrate of lobular distribution
    • Increased density along the dermal - subcutaneous transition, dermal perivascular and periadnexial regions
    • Dermal mucin and interface dermatitis may be present
  • No evidence of monoclonal TCB or TRG gene rearrangements
• Lyme disease (J Clin Pathol 2015;68:954):
  • Rare cases presenting as lobular panniculitis
    • Dense lymphocytic infiltrate in subcutaneous tissue with scattered plasma cells
      • Small to medium size and moderate atypia
    • No extension to overlying dermis or epidermis
  • Predominance of CD8+ cells
    • TIA1+
    • CD30-, CD56-
  • Identification of Borrelia burgdorferi DNA by PCR or positive serology
• Atypical lymphocytic lobular panniculitis (Am J Surg Pathol 2015;39:206):
  • Indolent condition with spontaneous regression
    • Controversial entity
  • Lobular infiltration of clonal, small to intermediate sized T cells and mild nuclear atypia
    • Usually less dense infiltrate
    • Adipocyte rimming is less frequent
    • Hemorrhage and karyorrhexis are usually absent
  • Good prognosis
• Primary cutaneous gamma delta T cell lymphoma (Surg Pathol Clin 2021;14:177):
  • Plaques, nodules and tumors with rapid progression and ulceration
  • Involvement of epidermis, dermis and subcutaneous tissue
    • Medium to large size lymphocytes with irregular nuclear contours, clumped chromatin and eosinophilic cytoplasm
  • CD3+, CD7+, CD5-, CD4-, CD8-
  • TIA1+, granzyme B+, perforin+
  • TCRδ+, TCRγ+, TCRβ (βF1)-
  • Poor prognosis
• Primary cutaneous CD30+ T cell lymphoproliferative disorders (Surg Pathol Clin 2021;14:177):
  • Multiple papules or solitary lesion
  • Monomorphic lymphoid infiltrate predominantly in dermis
    • May occur in hypodermis
  • CD3+, CD4 variable, CD8 variable
  • CD30 strong and diffuse
  • Indolent behavior
• Primary cutaneous peripheral T cell lymphoma, not otherwise specified (J Eur Acad Dermatol Venereol 2021;35:658):
  • Solitary or disseminated papulonodular or tumor lesions with rapid growth and necrosis
  • Nodular or diffuse infiltrate in dermis and subcutaneous tissue
    • Variable morphology, usually large, pleomorphic cells
  • Epidermotropism absent or focal
  • CD3+ / CD4- / CD8- or CD3+ / CD4+ / CD8-
    • CD8+ may also occur
  • Poor prognosis
    • 3 year overall survival: ~60%
    • 5 year overall survival: ~50%
• Acute myeloid leukemia involving skin (An Bras Dermatol 2018;93:216):
  • Variable clinical presentation
  • Diffuse infiltration of dermis and hypodermis
    • Neoplastic cells can rim adipocytes
• Extranodal NK / T cell lymphoma involving skin (Surg Pathol Clin 2021;14:177):
  • More common in adults
  • Ulcerated and necrotic tumors
  • Small to large atypical lymphocytes in an inflammatory and necrotic background
  • Angiocentricity and angioinvasion
  • Positive: CD2, CD56, TIA1, granzyme B, perforin, EBER
  • Negative: CD3ε, CD4, CD5, CD8
  • Poor prognosis

Which of the following is true about subcutaneous panniculitis-like T cell lymphoma?

1. Frequently presents with an aggressive clinical behavior
2. Localized or multiple subcutaneous nodules are the most common clinical presentation
3. Lymph nodes are usually involved at initial diagnosis
4. Somatic mutations of HAVCR2 are common

B. Localized or multiple subcutaneous nodules are the most common clinical presentation. Subcutaneous panniculitis-like T cell lymphoma usually presents as localized or multiple subcutaneous nodules, usually in the legs, arms or trunk and rarely with lymph node involvement. Germline mutations of HAVCR2 are classically described as a predisposing factor in up to 85% of patients.

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Reference: Subcutaneous panniculitis-like T cell lymphoma

Which of the following immunophenotypic pattern corresponds to subcutaneous panniculitis-like T cell lymphoma?

1. CD3-, CD4-, CD8+, TIA1-, granzyme B+, TCRγδ+
2. CD3-, CD4+, CD8+, TIA1-, granzyme B-, TCRγδ+
3. CD3+, CD4-, CD8+, TIA1+, granzyme B+, TCRαβ+
4. CD3+, CD4+, CD8-, TIA1+, granzyme B-, TCRαβ+

C. CD3+, CD4-, CD8+, TIA1+, granzyme B+, TCRαβ+. The typical immunophenotype is CD3+, CD4-, CD8+, TIA1+, granzyme B+ and TCRαβ+. The picture shows positivity in the neoplastic cells and highlights rimming of adipocytes.

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Reference: Subcutaneous panniculitis-like T cell lymphoma