Lymphoma and plasma cell neoplasms
T / NK cell disorders
Subcutaneous panniculitis-like T cell lymphoma (SPTCL)

Author: Robert E. LeBlanc, M.D.
Editorial Board Member Review: Genevieve M. Crane, M.D., Ph.D.
Deputy Editor Review: Debra Zynger, M.D.

Revised: 26 April 2018, last major update February 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: (Subcutaneous panniculitis-like T cell lymphoma [title]) SPTCL

Cite this page: LeBlanc, R.E. Subcutaneous panniculitis-like T cell lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBsubcutaneouspan.html. Accessed December 17th, 2018.
Definition / general
  • Peripheral T cell lymphoma derived from mature, postthymic cytotoxic αβ T cells
  • Presents as subcutaneous plaques and nodules; dissemination beyond subcutis is unusual
  • While most experience an indolent course, some patients can develop hemophagocytic lymphohistiocytosis (HLH)
Essential features
  • Rare adipotropic peripheral T cell lymphoma with a CD8 positive cytotoxic αβ immunophenotype that presents as subcutaneous plaques and nodules
  • Rarely disseminates beyond the subcutaneous fat and is generally associated with excellent overall survival
  • Subpopulation of patients can develop HLH, which is associated with worse survival
  • Histopathology can help distinguish subcutaneous panniculitis-like T cell lymphoma (SPTCL) from lupus erythematosus panniculitis and more aggressive lymphomas that involve the fat
  • Rare patients show overlapping features of lupus erythematosus panniculitis and SPTCL; they may also be at risk of developing HLH
Terminology
  • Subcutaneous panniculitis-like T cell lymphoma (SPTCL)
ICD coding
  • C86.3: Subcutaneous panniculitis-like T cell lymphoma
Epidemiology
  • Cases comprise < 1% of cutaneous T cell lymphomas
  • Higher incidence among women than men
  • Wide age range; median age at diagnosis in 30s
  • Substantial number of patients < 20 years old
Sites
  • Variable but most frequently involves the trunk, upper and lower extremities and buttocks
  • In contrast with how lupus erythematosus panniculitis presents, SPTCL is more likely to involve the buttocks and lower extremities and less likely to involve the face
Etiology
  • Not understood
  • Disagreement over whether or not SPTCL can evolve in the setting of lupus erythematosus panniculitis because rare patients exhibit overlapping clinical and histologic features
Clinical features
  • Can follow a many year history of what appears to be a benign, indolent panniculitis
  • Variably tender, erythematous subcutaneous plaques and nodules measuring up to several centimeters in diameter
  • Lesions may persist or resolve with lipoatrophy reminiscent of lupus erythematosus panniculitis
  • Dissemination beyond the skin and lymphadenopathy are rarely encountered
  • 20% of patients have antecedent or concomitant autoimmune disorders, most often systemic lupus erythematosus (Blood 2008;111:838)
  • Patients commonly present with fatigue, fever, weight loss and systemic symptoms
  • Reported risk of developing HLH is approximately 20% but may be as low as 6% in pediatric patients (Am J Surg Pathol 2008;32:1495, Ann Dermatol 2011;23:329, Pediatr Blood Cancer 2013;60:1165)
Diagnosis
  • Diagnosis requires strong clinical correlations to exclude lupus erythematosus panniculitis as well as other lymphoma
  • Patients with overlapping clinical and microscopic findings of SPTCL and lupus erythematosus panniculitis may have a risk of developing HLH (Am J Surg Pathol 2015;39:206)
  • No histologic features predict which patients are at risk of developing HLH
Laboratory
  • Patients can occasionally have a positive ANA (anti-nuclear antibody)
    • Does not favor the diagnosis of lupus erythematosus panniculitis
    • Patients with lupus panniculitis are less likely to have systemic lupus erythematosus
  • HLH 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis includes:
    • Fever
    • Splenomegaly
    • Cytopenias affecting ≥ 2 lineages
    • Hypertriglyceridemia or hypofibrinogenemia
    • Low or absent NK cell activity
    • Ferritin ≥ 500 µg/L
    • Soluble CD25 ≥ 2,400 U/mL
    • Evidence of hemophagocytosis in the bone marrow, spleen or lymph node
    • 5 of the criteria are necessary to establish the diagnosis in the absence of an HLH causing mutation (Pediatr Blood Cancer 2007;48:124)
Prognostic factors
  • Excellent 5 year overall survival of 91% in patients who do not develop HLH
  • Development of HLH is associated with decreased 5 year overall survival of 46% (Blood 2008;111:838)
Case reports
Treatment
  • In the absence of HLH, patients are managed conservatively
  • Treatment is tailored to each patient; an array of therapies exist including localized therapies (radiotherapy and intralesional steroids) and systemic therapies (steroids, biologic antineoplastic agents such as bexarotene or denileukin diftitox and HDAC inhibitors)
  • More aggressive disease is sometimes treated with an intensive regimen of biologic agents, HDAC inhibitors or single agent chemotherapy
Clinical images

Images hosted on other servers:

Thigh

Clinical, micro and immuno

Microscopic (histologic) description
  • Lobular panniculitis-like infiltrate with background fat necrosis, karyorrhexis and histiocytes that contain karyorrhectic debris or lipids and sometimes exhibit erythrophagocytosis
  • Lymphocytes rim adipocytes, characteristically disrupting the adipocyte cell membranes and often appearing within the adipocyte lobules
  • Lymphocytes are at least mildly enlarged and exhibit nuclear hyperchromasia and contour irregularity
  • Plasma cells, lymphoid follicle and hyaline lipomembranous fat necrosis are less conspicuous or absent in SPTCL in comparison to lupus erythematosus panniculitis
  • Biopsies from older lesions can show granulomatous inflammation, lipomembranous fat necrosis and or fibrosis in lieu of adipotropic lymphoma
  • Epidermotropism is rare and the intraepidermal cells are sparse and do not form Pautrier microabscesses in contrast with developed lesions of mycosis fungoides
  • Hemophagocytosis should be assessed in the bone marrow, spleen or lymph node and not the skin per HLH 2004 criteria (Pediatr Blood Cancer 2007;48:124)
Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Robert E. LeBlanc, M.D.

Low power view of a dense lymphoid infiltrate

High power view of adipocytes

H&E

Ki67 hotspot


TCRβF1

CD8

TIA1

Positive stains
  • Ki67 hotspots (foci of increased expression enriched with CD8 positive cytotoxic T cells rimming adipocytes) can be a helpful clue to the diagnosis in samples obscured by necrosis or an accompanying polymorphous inflammatory infiltrate
  • Adipotropic lymphocytes express TCRβF1, CD8 and cytotoxic markers such as TIA1 and granzyme
Negative stains
  • TCRγ staining should raise consideration for primary cutaneous gamma delta T cell lymphoma
  • EBER staining of lesional cells should raise consideration for extranodal NK / T cell lymphoma, nasal type
  • CD4 should raise consideration for mycosis fungoides or secondary subcutaneous involvement by an extracutaneous peripheral T cell lymphoma
  • CD30 staining of ≥ 75% of the infiltrate should raise consideration for anaplastic large cell lymphoma
  • CD56 staining may raise concern for primary cutaneous gamma delta T cell lymphoma, extranodal NK / T cell lymphoma or blastic plasmacytoid dendritic cell neoplasm
  • CD123 plasmacytoid dendritic cell clusters are much more common and easier to identify in lupus erythematosus panniculitis; however, they have been identified in some clinically annotated cases of SPTCL (Histopathology 2013;62:1057, Am J Surg Pathol 2016;40:745)
Molecular / cytogenetics description
  • Clonal rearrangement of the T cell receptor can be a helpful clue to the diagnosis whenever the histologic findings are nonspecific and there is strong clinical consideration for a diagnosis of SPTCL
  • Identification of a clonal T cell receptor gene rearrangement in a single biopsy is considerably less specific for the diagnosis of lymphoma than identification of the same clone in multiple biopsies taken at different times or from different sites
  • Clones can persist in atypical lymphocytic lobular panniculitis and other T cell dyscrasias that do not behave as lymphoma
Differential diagnosis
  • Atypical lymphocytic lobular panniculitis: indolent, clonal T cell dyscrasia with relatively subtle lymphoid atypia and inconspicuous erythrocyte phagocytosis by histiocytes, an absence of distinct adipocyte rimming, less extensive fat necrosis and a propensity for spontaneous clinical resolution and recurrence (J Cutan Pathol 2008;35:947); this diagnosis is somewhat controversial, however the features described are distinct from lupus erythematosus panniculitis and lymphoma.
  • Extranodal NK / T cell lymphoma, nasal type: while skin limited disease has been associated with improved survival over variants that show extracutaneous involvement at the time of diagnosis, this lymphoma is much more aggressive than SPTCL and more likely to show angiodestruction as opposed to karyorrhexis and adipocyte rimming; this lymphoma expresses EBER (Hum Pathol 2017;68:61)
  • Lupus erythematosus panniculitis: ubiquitously low Ki67 expression without hotspots, no lymphoid cytologic atypia, no distinct rimming (the infiltrate splays adipocyte lobules)
  • Mycosis fungoides: can mimic SPTCL in lesions that involve the fat; however, MF is more likely to be CD4+ / CD8- and the clinical history alone will often distinguish these entities
    • Clonality studies comparing patches to subcutaneous disease can be considered in the unlikely circumstance that the clinical history does not clarify the diagnosis
  • Peripheral T cell lymphoma, NOS: may require clinical correlations; often either CD4+ / CD8- or CD4- / CD8-
  • Primary cutaneous anaplastic large cell lymphoma: usually larger cells with greater pleomorphism and CD30 expression in ≥ 75% of cells
    • Infiltrate is not confined to fat lobules
    • No rimming
  • Primary cutaneous gamma delta T cell lymphoma: early lesions may closely mimic SPTCL; however, this often aggressive lymphoma is comprised of cells that express TCRγ
Board review question #1
Which of the following stains (when positive) would exclude the diagnosis of subcutaneous panniculitis-like T-cell lymphoma?

  1. Granzyme
  2. Ki67
  3. TCRβF1
  4. TCRγ
Board review answer #1
D. Primary cutaneous gamma delta T cell lymphoma is a much more aggressive disease that had been subsumed under the category of SPTCL until 2008. Staining of all newly diagnosed cases of SPTCL with an immunohistochemical stain for TCRγ is strongly advised to exclude a gamma delta T cell lymphoma.
Board review question #2
Which of the following findings in SPTCL has the greatest impact on prognosis?

  1. Hemophagocytic lymphohistiocytosis
  2. High Ki67 expression
  3. Involvement of the buttock and lower extremities
  4. Presence of splenomegaly
Board review answer #2
A. HLH is associated with a significant decline in overall 5 year survival in patients with SPTCL. Otherwise, the disease is usually associated with an indolent course. Some patients may have splenomegaly; and while this finding sometimes presages the development of HLH, additional criteria need to be met to establish the diagnosis. Splenomegaly in SPTCL is generally not attributed to splenic involvement by lymphoma. SPTCL usually exhibits high Ki67 expression throughout the lesion or Ki67 hotspots enriched for cytotoxic CD8+ lymphocytes rimming adipocytes.