Home > Lymphoma & related disorders > Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma

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Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma

Authors: Mario L. Marques-Piubelli, M.D., Maria C. Ferrufino-Schmidt, M.D., Roberto N. Miranda, M.D.

Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.

Editor-in-Chief: Patricia Tsang, M.D., M.B.A.

Last author update: 7 August 2020

Last staff update: 24 November 2023

Copyright: 2001-2024, PathologyOutlines.com, Inc.

PubMed search: Epidermotropic CD8+ lymphoma

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Table of Contents

Cite this page: Marques-Piubelli ML, Ferrufino-Schmidt MC, Miranda RN. Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBCD8epidermotropic.html. Accessed April 16th, 2024.

Definition / general

Cutaneous T cell lymphoma (CTCL) with marked epidermotropism by CD8+ cytotoxic T cells and aggressive clinical behavior (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425, Radiology 1991;178:907, Am J Pathol 1999;155:483)
Included as provisional entity in 2008 and maintained as provisional in the 2017 revised WHO; first described in 1999 (Elder: WHO Classification of Skin Tumours, 4th Edition, 2018, Histopathology 2015;67:425, Am J Pathol 1999;155:483)

Essential features

Cutaneous T cell lymphoma (CTCL) with marked epidermotropism by CD8+ cytotoxic T cells and aggressive clinical behavior (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Usually have generalized skin involvement (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425)
Unfavorable prognosis and aggressive clinical course (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)

ICD coding

ICD-O: 9709/3 - Cutaneous T cell lymphoma, NOS

Epidemiology

Rare, < 1% of all cutaneous T cell lymphoma (J Am Acad Dermatol 2012;67:748, J Am Acad Dermatol 2010;62:300)
More common in elderly: sixth and seventh decade (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, Am J Pathol 1999;155:483)
M:F = 3:1 (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, Am J Pathol 1999;155:483)
No predisposing factors (Mod Pathol 2017;30:761)

Sites

Usually have generalized skin involvement (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425)
- Variable distribution in cases with localized involvement: upper / lower extremities, trunk, head and neck (Mod Pathol 2017;30:761)
Oral mucosa or perioral skin involvement may be present (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
High tendency to spread to extranodal sites (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
- Lung, testis, CNS, liver, spleen and heart
Lymph node and bone marrow involvement are rare (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425, Am J Pathol 1999;155:483)

Clinical features

Rapidly progressive (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Diffuse eruptive papules, patches, plaques, nodules and tumors with central ulceration and necrosis (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Uncommon presentation as superficial hyperkeratotic patches and plaques clinically resembling pagetoid reticulosis of the Ketron-Goodman type (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, J Am Acad Dermatol 2010;62:300)

Diagnosis

Combination of clinical, histopathological and immunohistochemical features (J Am Acad Dermatol 2012;67:748)
Diagnostic criteria (J Am Acad Dermatol 2012;67:748)
- Constant features
  - Aggressive clinical course with few weeks evolution
  - Widespread ulcerated papules, plaques and tumors without precursor lesion
  - Epidermotropism and nodular or diffuse dermal pleomorphic T cell infiltrate
  - CD8+ / CD4-
- Variable features
  - Pyoderma gangrenosum-like, pagetoid reticulosis-like and annular erythematous scaling patches
  - Spongiosis, blisters and necrosis
  - Deep lymphoid infiltrate, angiocentrism and angiodestruction
  - Variable expression of CD2, CD7, CD15, CD45 and CD56

Prognostic factors

Unfavorable prognosis and aggressive clinical course (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
- Median survival: 22 - 32 months
- 5 year overall survival: 18 - 32%
Worst prognosis in patients presenting with tumors at diagnosis (Mod Pathol 2017;30:761)
Survival not influenced by cell size (small versus large), distribution (localized versus disseminated) or immunophenotype groups (Mod Pathol 2017;30:761)

Case reports

16 year old boy with primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma with cerebral infiltration and treated with cord blood stem cell transplant (SCT) (Intern Med 2018;57:2051)
19 year old woman with primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma simulating pyoderma gangrenosum (Clin Exp Dermatol 2009;34:e261)
29 year old woman with primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma and homozygous mutation in SAMHD1 (JAAD Case Rep 2015;1:227)
47 year old man with primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma and complete durable remission after autologous and allogeneic hematopoietic stem cell transplantation (JAAD Case Rep 2017;3:196)
61 year old man with primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma and history of psoriasis (Ann Dermatol 2018;30:255)
68 year old man with lupus-like initial clinical presentation (Indian Dermatol Online J 2019;10:298)
72 year old man with primary cutaneous aggressive epidermotropic CD8+ cytotoxic T cell lymphoma of the ear (J Laryngol Otol 2007;121:503)

Treatment

No definite successful therapy available
Multiagent chemotherapy: CHOP (cyclophosphamide, hydroxydorubicin, vincristine and prednisone), CHOEP (cyclophosphamide, hydroxydorubicin, vincristine, etoposide and prednisone), hyper-CVAD (hyper-cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine) and MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin) (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761)
- Unsatisfactory and usually partial response
Total skin electron beam therapy with or without oral retinoid (e.g. bexarotene) (J Am Acad Dermatol 2012;67:748, J Am Acad Dermatol 2010;62:300)
- Partial response and some cases with complete clearance
Allogeneic or autologous stem cell transplant (SCT) (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, J Am Acad Dermatol 2010;62:300)
- Setting of unresponsive or relapse after multiagent chemotherapy or early use of combined intensive chemotherapy and SCT

Microscopic (histologic) description

Epidermotropism (particularly in basal layer) usually followed by a pagetoid or lichenoid pattern (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425, Am J Pathol 1999;155:483)
- Rare cases with absence of epidermotropism (J Am Acad Dermatol 2012;67:748)
Dermal infiltrate with lymphocytes of variable size (small to large), pleomorphic cytology, nodular or diffuse pattern and deep extension into dermis down to subcutaneous (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, Am J Pathol 1999;155:483)
Folliculotropism, syringotropism, angiocentrism and angioinvasion may be present (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300)
Other findings: acanthosis, spongiosis, blistering and necrosis (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)

Microscopic (histologic) images

Contributed by Roberto N. Miranda, M.D.

Skin epidermotropism and dermal infiltrate

Epidermotropism with intraepidermal cluster

Lymphoma at the dermoepidermal junction

Large pleomorphic cells

CD3 positivity

CD4 negativity of epidermotropic cells

CD7 positivity of epidermotropic cells

CD8 positivity of epidermotropic cells

TIA1 positivity of lymphoma cells

Proliferation marker Ki67

Pagetoid reticulosis

Microabscess of Pautrier in pagetoid reticulosis

CD3 in pagetoid reticulosis

CD8 in pagetoid reticulosis

βF1 pagetoid reticulosis

Folliculotropism in CD8 epidermotropic TCL

Epidermotropism in CD8 epidermotropic TCL

Epidermotropic small lymphoma cells

Liver involvement by CD8 cytotoxic TCL

CD3 positive lymphoma cells

CD8 positive lymphoma cells

Positive stains

CD3, CD8 and CD45RA (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
- Very rare cases of double CD4 / CD8 negativity (Mod Pathol 2017;30:761)
Cytotoxic granules: TIA1, granzyme B and perforin (Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Variable CD2 and CD7 (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483, Oncol Ther 2016;4:199)
- CD2- / CD7+: associated with rapid progression
- CD2+ / CD7-: less aggressive clinical course
BCL2 (Am J Pathol 1999;155:483)
βF1 (Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Ki67 (often > 75%) (J Am Acad Dermatol 2012;67:748, Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425)

Negative stains

Molecular / cytogenetics description

Clonal TR rearrangement (J Am Acad Dermatol 2012;67:748, Mod Pathol 2017;30:761, J Am Acad Dermatol 2010;62:300, Am J Pathol 1999;155:483)
Haploinsufficiency for TP53 (Ann Dermatol 2018;30:255)

Sample pathology report

Ulcerated plaque of the trunk, skin punch biopsy:
- Primary cutaneous T cell lymphoma, most consistent with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma (see comment)
- Comment: Section shows an adequate skin punch biopsy with intense epidermotropism, focal epidermal necrosis, acanthosis and spongiosis. There is an extensive, nodular and diffuse dermal infiltrate composed of variably sized, pleomorphic lymphocytes with irregular nuclear contours, hyperchromatic nuclei and scant cytoplasm. Immunohistochemical studies show that the abnormal lymphocytes are diffusely positive for CD3, CD7, CD8, CD45RA, TIA1, T cell receptor beta (βF1) and granzyme B. The atypical cells are negative for CD2, CD4, CD5, CD56, EBER, CD30, T cell receptor gamma / delta and ALK1. The Ki67 proliferation index is approximately 70%. According to clinical notes, the patient is a 63 year old man with history of hypertension. The patient presented to the department of dermatology with a 5 week history of ulcerated plaques, papules and nodules in the upper and lower limbs, trunk, head, neck, tongue and perioral area. A computed tomography (CT) showed multiple nodules in liver, without evidence of lymphadenopathy. The final diagnosis is most consistent with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma.

Differential diagnosis

Lymphomatoid papulosis (LyP) type D (Am J Clin Pathol 2013;139:491, Histopathology 2015;67:425):
- Clinical presentation as waxing and waning papules and nodules
- Some cases are histologically indistinguishable from primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma
- Wedge shaped infiltrate of medium size pleomorphic T cells with cytotoxic phenotype
- Large cells with strong and uniform expression of CD30
- May be associated or preceded by other lymphoid malignancies such as mycosis fungoides
- Good prognosis
Primary cutaneous anaplastic large cell lymphoma (Am J Clin Pathol 2013;139:491):
- Large cells with strong and uniform expression of CD30
- Localized disease
Subcutaneous panniculitis-like T cell lymphoma (Am J Clin Pathol 2013;139:491, Am J Surg Pathol 2004;28:719):
- Solitary or multiple infiltrated subcutaneous nodules or deeply seated plaques
- Dissemination to extracutaneous sites is rare
- Overlying dermis and epidermis typically uninvolved
- Pleomorphic cells admixed with histiocytes
- Excellent prognosis
Primary cutaneous acral CD8+ T cell lymphoma (Oncol Ther 2016;4:199):
- Provisional entity according to the WHO
- Indolent clinical presentation of nodules and papules in ears, nose and lower limbs
- Absence of ulceration and angiocentricity
- Epidermis is often spared and has minimal epidermotropism
- Medium sized lymphocytes
- CD2 and CD5 usually positive
Extranodal NK / T cell lymphoma, nasal type (Am J Clin Pathol 2013;139:491, Am J Surg Pathol 2004;28:719):
- Most cases with NK phenotype (CD3ε+ / CD56+)
- Small to large atypical cells with irregular nuclear folding
- EBER+
Solitary pagetoid reticulosis (Woringer-Kolopp disease) (Histopathology 2015;67:425):
- Solitary or localized hyperkeratotic erythematous patches
- Marked pagetoid epidermotropism of medium and atypical mononuclear cells
- Either CD4+ / CD8+ or CD4- / CD8-
- Treatment: topical corticosteroids, localized radiation, psoralen plus ultraviolet A (PUVA) and excision
Primary cutaneous γδ T cell lymphoma (Am J Clin Pathol 2013;139:491, Mod Pathol 2017;30:761, Am J Surg Pathol 2004;28:719):
- Composed of mature γδ T cells
- Uncommon epidermotropism
- Medium to large shape with clumped chromatin
- No involvement of mucosae; rare involvement of extranodal sites
Mycosis fungoides (J Am Acad Dermatol 2012;67:748, Histopathology 2015;67:425, J Am Acad Dermatol 2010;62:300, Oncol Ther 2016;4:199):
- Longer clinical history with typical progression: patch → plaque → tumor
- Cerebriform morphology
- Frequent lack of CD7
- Rare mucosal involvement
- Common lymph node involvement with variable histologic appearance and pathologic staging
- Rare ulceration, angiocentricity and angioinvasion
- Needs systemic chemotherapy in longstanding and advanced disease
- Good prognosis
Secondary cutaneous involvement of peripheral T cell lymphoma (Am J Clin Pathol 2013;139:491):
- Exclusion diagnostic: always rule out the other defined entities
- Small size morphology and CD4+
- Secondary skin involvement; unusual confined to cutaneous sites

Additional references

Medeiros: Diagnostic Pathology - Lymph Nodes and with Extranodal Lymphomas, 2nd Edition, 2017

Board review style question #1

CD3+ / CD4- / CD7- / CD8+ / CD30- / EBER-
CD3+ / CD4- / CD7+ / CD8+ / CD30- / EBER+
CD3+ / CD4+ / CD7+ / CD8+ / CD30- / EBER+
CD3+ / CD4+ / CD7+ / CD8+ / CD30+ / EBER-

Board review style answer #1

A. CD3+ / CD4- / CD7- / CD8+ / CD30- / EBER-

Comment Here

Reference: Primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma

Board review style question #2

Pyoderma gangrenosum-like
Spongiosis, blistering and necrosis
Variable expression of CD2, CD4, CD5, CD7 and CD8
Widespread ulcerated papules, plaques and tumors without precursor lesion

Board review style answer #2

D. Widespread ulcerated papules, plaques and tumors without precursor lesion

Comment Here

Reference: Primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma