Lymphoma & related disorders
Mature T/NK cell disorders
Cutaneous / soft tissue involvement
Primary cutaneous PTCL, NOS
Editorial Board Member: Julie Feldstein, M.D.
Last staff update: 5 December 2024 (update in progress)
Copyright: 2021-2024, PathologyOutlines.com, Inc.
PubMed Search: Primary cutaneous PTCL, NOS
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Marques-Piubelli ML, Murga-Zamalloa CA, Miranda RN. Primary cutaneous PTCL, NOS. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaptclnos.html. Accessed December 17th, 2024.
Definition / general
- Primary cutaneous peripheral T cell lymphoma, not otherwise specified (PC PTCL, NOS) is a rare and aggressive type of cutaneous T cell lymphoma that primarily involves the skin and does not have evidence of systemic involvement at the time of diagnosis (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, Case Rep Oncol 2018;11:212, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213, Blood 2019;133:1703, Histopathology 2014;64:171, J Am Acad Dermatol 2019;80:1771, J Eur Acad Dermatol Venereol 2021;35:658)
- Included as a new entity in the 5th edition of the WHO and a diagnosis of exclusion after other better defined primary cutaneous T cell lymphomas are ruled out
- In the International Consensus Classification, PC PTCL is classified within the PTCL, NOS category (Leukemia 2022;36:1720, Blood 2022;140:1229, Hematol Oncol 2021;39:46, Ann Oncol 2018;29:iv30)
- Diagnosis requires exclusion of other primary cutaneous T cell lymphomas, such as large cell transformation of mycosis fungoides, primary cutaneous gamma delta T cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma, primary cutaneous acral CD8+ T cell lymphoproliferative disorder and primary cutaneous CD4+ small / medium T cell lymphoproliferative disorder
Essential features
- Primary cutaneous peripheral T cell lymphoma, not otherwise specified (PC PTCL, NOS) is a rare and aggressive type of cutaneous T cell lymphoma that primarily involves the skin and does not have evidence of systemic involvement at the time of diagnosis (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, Case Rep Oncol 2018;11:212, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213, Blood 2019;133:1703, Histopathology 2014;64:171, J Am Acad Dermatol 2019;80:1771, J Eur Acad Dermatol Venereol 2021;35:658)
- Aggressive clinical course (Diagnostics (Basel) 2020;10:629, JAAD Case Rep 2020;6:1342, Case Rep Oncol Med 2015;2015:429068, J Am Acad Dermatol 2016;75:992, Blood 2019;133:1703, J Eur Acad Dermatol Venereol 2021;35:658)
- Localized or generalized, infiltrating, erythematous or violaceous plaque-like lesions or papules
- PC PTCL, NOS is a diagnosis of exclusion and therefore other types of primary cutaneous T cell lymphomas should be ruled out before a diagnosis is rendered (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, J Am Acad Dermatol 2019;80:1771)
- No evidence of extracutaneous disease (lymph node, bone marrow or visceral involvement) for at least 6 months after the diagnosis
Terminology
- Cutaneous peripheral T cell lymphoma, not otherwise specified
ICD coding
Epidemiology
- Rare type of cutaneous T cell lymphoma (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, J Am Acad Dermatol 2016;75:992)
- ~2% of all cutaneous lymphomas
- Usually occurs in adults and elderly and has no gender predilection (Diagnostics (Basel) 2020;10:629, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213)
Sites
- Trunk, head and neck, upper or lower extremities (J Am Acad Dermatol 2016;75:992)
Pathophysiology
- Due to the rarity of reported cases, the pathophysiology is not well understood
Clinical features
- Aggressive clinical course (Diagnostics (Basel) 2020;10:629, JAAD Case Rep 2020;6:1342, Case Rep Oncol Med 2015;2015:429068, J Am Acad Dermatol 2016;75:992, Blood 2019;133:1703, J Eur Acad Dermatol Venereol 2021;35:658)
- Localized or generalized, infiltrating, erythematous or violaceous plaque-like lesions or papules
- May share dermoscopic features with benign plaque-like conditions
- May present or progress as multiple masses or tumors (ulcerated or not), usually immobile and indurated
- Rapid evolution: ~6 months
- Itching and pain may be present
- Association with secondary infection
- Localized or generalized, infiltrating, erythematous or violaceous plaque-like lesions or papules
- Constitutional symptoms are uncommon (Diagnostics (Basel) 2020;10:629, J Am Acad Dermatol 2016;75:992)
- Absence of systemic involvement at the time of diagnosis (Diagnostics (Basel) 2020;10:629)
Diagnosis
- Other better defined primary cutaneous T cell lymphomas should be excluded prior to rendering a diagnosis for PC PTCL, NOS (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, J Am Acad Dermatol 2019;80:1771)
- No evidence of extracutaneous disease (lymph node, bone marrow or visceral involvement) for at least 6 months after diagnosis
Laboratory
- HTLV1 negative (Acta Derm Venereol 2019;99:1176)
Prognostic factors
- Median overall survival (OS): 2 - 6 years (J Am Acad Dermatol 2016;75:992, Acta Derm Venereol 2019;99:1176, Blood 2003;102:2213, J Eur Acad Dermatol Venereol 2021;35:658)
- 3 year OS: ~60%
- 5 year OS: ~20 - 50%
- Median disease free survival: 8 months (Blood 2003;102:2213)
- Tumor site may be implicated in the prognosis (J Am Acad Dermatol 2019;80:1771)
Case reports
- 39 year old man with PC PTCL, NOS mimicking periorbital cellulitis (Int J Dermatol 2023;62:e125)
- 67 year old woman with PC PTCL successfully treated with bexarotene monotherapy (Case Rep Oncol 2018;11:212)
- 72 year old woman with PC PTCL, NOS of the eyelid with clinical remission after combination of chemotherapy with etoposide and cyclophosphamide, vincristine, prednisone (COP) (Diagnostics (Basel) 2020;10:629)
- 73 year old man with double negative (CD4- / CD8-) PC PTCL (Acta Derm Venereol 2019;99:1176)
- 78 year old woman with PC PTCL presenting as rapidly growing nodule on shoulder (Case Rep Oncol Med 2015;2015:429068)
Treatment
- Anthracycline based regimen or hematopoietic stem cell transplantation (Diagnostics (Basel) 2020;10:629, Case Rep Oncol Med 2015;2015:429068)
- CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
- CHOEP (CHOP plus etoposide)
- Vorinostat (Acta Derm Venereol 2019;99:1176)
- Bexarotene (Case Rep Oncol 2018;11:212)
Clinical images
Contributed by Roberto N. Miranda, M.D.
Erythematous ulcerated tumor mass lesions
Microscopic (histologic) description
- Predominantly dermal atypical lymphoid infiltrate (superficial or profound) (Diagnostics (Basel) 2020;10:629, Case Rep Oncol Med 2015;2015:429068, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213, J Eur Acad Dermatol Venereol 2021;35:658)
- Diffuse (more common), lichenoid or nodular patterns
- Variable size (ranges from medium to large cell size morphology), round to oval or irregular nuclei with vesicular chromatin
- Absent or discrete epidermotropism, angiocentrism and adnexotropism
- Background cells include few histiocytes, eosinophils and plasma cells
- High mitotic activity is common (Diagnostics (Basel) 2020;10:629)
Microscopic (histologic) images
Contributed by Roberto N. Miranda, M.D.
Atypical dermal infiltrate
Absent or minimal epidermotropism
CD3 positive
CD4 positive
CD8 negative
Partial loss of CD7
CD30 negative
Atypical lymphoid infiltrate
TCR βF1 positive
TCR delta negative
Positive stains
- Pan-T cell markers (Diagnostics (Basel) 2020;10:629, Acta Derm Venereol 2019;99:1176, Case Rep Oncol Med 2015;2015:429068, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213, J Am Acad Dermatol 2019;80:1771)
- CD45 (Case Rep Oncol 2018;11:212)
- GATA3 (J Eur Acad Dermatol Venereol 2021;35:658)
- Associated with solitary lesions on the limbs
- TCR βF1 (J Am Acad Dermatol 2016;75:992)
- High proliferation index: Ki67 ~30 - 90% (Diagnostics (Basel) 2020;10:629, Acta Derm Venereol 2019;99:1176)
Negative stains
- Aberrant T cell phenotype (Diagnostics (Basel) 2020;10:629, Acta Derm Venereol 2019;99:1176, J Am Acad Dermatol 2016;75:992, Blood 2003;102:2213, J Am Acad Dermatol 2019;80:1771)
- CD56 (Diagnostics (Basel) 2020;10:629, Case Rep Oncol Med 2015;2015:429068, Blood 2003;102:2213)
- B cell markers: CD20, PAX5, CD79b (Diagnostics (Basel) 2020;10:629)
- T follicular helper markers: CD10, BCL6, PD-1, ICOS (Diagnostics (Basel) 2020;10:629, J Am Acad Dermatol 2016;75:992)
- CD30 (Diagnostics (Basel) 2020;10:629, JAAD Case Rep 2020;6:1342, Case Rep Oncol Med 2015;2015:429068, J Am Acad Dermatol 2016;75:992, Histopathology 2014;64:171)
- Rare positive cells may be observed
- Granzyme B (Acta Derm Venereol 2019;99:1176, Blood 2003;102:2213)
- TCR γ / δ (J Am Acad Dermatol 2016;75:992)
- EBER (Acta Derm Venereol 2019;99:1176)
Molecular / cytogenetics description
- Monoclonal TCR gene rearrangements are usually detected (Diagnostics (Basel) 2020;10:629, Int J Dermatol 2023;62:e125, JAAD Case Rep 2020;6:1342, Acta Derm Venereol 2019;99:1176, J Am Acad Dermatol 2016;75:992)
Sample pathology report
- Anterior trunk, skin punch:
- Involved by T cell lymphoma (see comment)
- Comment: According to clinical notes, this is a 68 year old man with a history of multiple skin patches in trunk, head and neck and lower extremities of a very recent onset (past 3 months). The patient has no previous medical history of cutaneous lesions.
- Histologic sections of a punch biopsy show a diffuse and dense dermal infiltrate of medium to large sized lymphocytes. Most lymphocytes show irregular nuclear contours, vesicular chromatin and scant cytoplasm. Epidermotropism and angiocentrism are not observed. Scattered mitotic figures are noted. Few histiocytes and plasma cells are noted in the background.
- Immunohistochemical studies reveal the neoplastic cells are positive for CD2, CD3, CD4 and TCR βF1. The large abnormal cells are negative for CD5, CD7, CD8, CD10, CD30, CD56, BCL6, EBER, PD-1, TdT and TCR delta.
- Concurrent imaging findings show no evidence of systemic disease and concurrent flow cytometry immunophenotype of the bone marrow and peripheral blood show polytypic T cells (by TRBC1). Clinical correlation and follow up is recommended.
- The morphological, immunohistochemical and molecular features are those of a T cell lymphoma and if this case is localized to cutaneous sites, it is consistent with cutaneous T cell lymphoma. It is necessary to exclude the possibility of secondary involvement by primary (nodal) T cell lymphoma or primary leukemic T cell lymphoma (such as ATLL). Additional surveillance of lymph node involvement and serological testing for HTLV1 is required.
Differential diagnosis
- Mycosis fungoides, large cell transformation (Hematol Oncol 2021;39:46, Am J Clin Pathol 2013;139:491):
- Characteristic disease evolution: patch → plaque → tumor over many years; rapid progression after large cell transformation
- Cerebriform nuclear irregularities and frequent epidermotropism; cerebriform morphology tends to disappear with large cell transformation, where large cells can show pleomorphism, vesicular nuclei and mitoses
- Aberrant T cell phenotype with frequent loss of CD7 and CD26
- Treatment: skin directed therapies for early stages and systemic therapy for advanced disease; chemotherapy can be indicated for large cell transformation
- Favorable prognosis for patch and plaque stage disease; unfavorable for tumor stage disease
- Systemic involvement of peripheral T cell lymphoma, not otherwise specified (J Am Acad Dermatol 2016;75:992, J Am Acad Dermatol 2019;80:1771):
- Exclusion diagnosis: evidence of systemic nodal involvement in the clinical history preceding the cutaneous lesions or at the time of the diagnosis
- Higher age when compared to PC PTCL, NOS
- Elevated lactate dehydrogenase and international prognostic index (IPI) > 2
- Overlapping of histologic, cell morphology and immunophenotype
- Poor outcomes
- Primary cutaneous CD4 positive small or medium T cell lymphoproliferative disorder (Semin Cutan Med Surg 2018;37:39):
- Slow growing single plaque / nodule on head and neck or upper trunk
- Small to medium sized lymphocytes with minimal to moderate atypia, arranged in diffuse or nodular pattern
- Discrete epidermotropism
- CD3+, CD4+, CD8+, PD-1+, BCL6+, CXCL13+
- Low Ki67 rate
- Benign clinical course; corticoids or local radiation can control the disease (Int J Dermatol 2024 Jul 2 [Epub ahead of print])
- Cutaneous involvement of adult T cell lymphoma / leukemia (Semin Diagn Pathol 2020;37:81, Mod Pathol 2018;31:1046):
- Association with human T lymphotropic virus type 1 (HTLV1)
- Skin is commonly affected in cases of ATLL (up to ~70%) and can be associated with no leukemic presentation
- Variable skin lesion: patches, plaques, nodules, tumors, erythroderma and purpura
- Variable histologic presentation: from superficial dermal infiltrate with epidermotropism, nodular to diffuse dermal infiltration
- CD3+, CD4+, CD8+, CD25+, CCR4+
- Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T cell lymphoma (Mod Pathol 2017;30:761):
- Primary cutaneous gamma delta T cell lymphoma (Am J Clin Pathol 2013;139:491):
- Clonal proliferation of gamma delta lymphocytes with a cytotoxic phenotype
- Primarily cutaneous but mucosal and extranodal sites usually involved
- Medium - large sized lymphocytes with irregular nuclear contours and clumped chromatin
- Epidermotropism is variable
- CD2+, CD3+, CD4-, CD8-, CD56 variable, granzyme B+, TCR γ / δ+, TCR βF1-
- Good prognosis in predominantly epidermotropic disease; poor prognosis in cases affecting dermis and subcutaneous tissue (Surg Pathol Clin 2021;14:177, J Dermatol Sci 2018;89:88, Am J Surg Pathol 2017;41:431, Am J Surg Pathol 2017;41:204)
- Angioimmunoblastic T cell lymphoma (Blood 2017;129:1095):
- Nodal based lymphoma; patients usually present with systemic disease
- Histologic presentation shows scattered atypical cells admixed with a reactive polymorphous infiltrate and prominent proliferation of high endothelial venules
- εCD3, CD4, CXCL13, CD10, PD-1 (CD279), ICOS and BCL6
- Unique mutational profile
- TET2, DNMT3, IDH2 and RHOA
- T prolymphocytic leukemia (Blood 2019;134:1132):
Additional references
Board review style question #1
Which of the following is true about primary cutaneous peripheral T cell lymphoma, not otherwise specified (PC PTCL, NOS)?
- An exclusion diagnosis and no evidence of extracutaneous disease should be present for at least 6 months after diagnosis
- Epidermotropism is common
- Frequently presents with an indolent clinical behavior
- Prognosis is usually favorable
Board review style answer #1
A. It is a diagnosis of exclusion and no evidence of extracutaneous disease should be present for at least 6 months after diagnosis. Answer B is incorrect because epidermotropism is usually absent in PC PTCL, NOS. Answer C is incorrect because the disease usually has an aggressive clinical course and answer D is incorrect because the disease has poor prognosis.
Comment Here
Reference: Primary cutaneous PTCL, NOS
Comment Here
Reference: Primary cutaneous PTCL, NOS
Board review style question #2
Which of the following immunophenotypic patterns is most consistent with primary cutaneous peripheral T cell lymphoma, not otherwise specified?
- CD2+ / CD3+ / CD4- / CD8- / CD10- / CD30- / PD-1+ / TCR gamma / delta+
- CD2+ / CD3+ / CD4+ / CD8- / CD10- / CD30+ / PD-1- / TCR gamma / delta-
- CD2+ / CD3+ / CD4+ / CD8- / CD10- / CD30- / PD-1- / TCR gamma / delta-
- CD2+ / CD3+ / CD4- / CD8+ / CD10- / CD30- / PD-1+ / TCR gamma / delta+
Board review style answer #2
C. CD2+ / CD3+ / CD4+ / CD8- / CD10- / CD30- / PD-1- / TCR gamma / delta-. The most typical immunophenotype is CD2+ / CD3+ / CD4+ / CD8- / CD10- / CD30- / PD-1- / TCR gamma / delta-. Answer A is incorrect because CD4 is usually positive and PD-1 and TCR gamma / delta are usually negative. Answer B is incorrect because CD30 is usually negative. Answer D is incorrect because CD4 is usually positive and CD8, PD-1 and TCR gamma delta are usually negative.
Comment Here
Reference: Primary cutaneous PTCL, NOS
Comment Here
Reference: Primary cutaneous PTCL, NOS
