Skin nonmelanocytic tumor
Lymphoma and related disorders (see also Lymphoma chapter)
T cell / NK cell neoplasms
Lymphomatoid papulosis


Topic Completed: 6 April 2020

Minor changes: 6 April 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed search: Lymphomatoid papulosis skin [title]

Mario L. Marques-Piubelli, M.D.
Roberto N. Miranda, M.D.
Page views in 2019: 5,024
Page views in 2020 to date: 5,893
Cite this page: Marques-Piubelli M, Ferrufino-Schmidt M, Miranda R. Lymphomatoid papulosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skintumornonmelanocyticlymphomatoidpapulosis.html. Accessed October 29th, 2020.
Definition / general
Essential features
ICD coding
  • ICD-O: 9718/1 - lymphomatoid papulosis
Epidemiology
Sites
Etiology
  • No etiologic factors identified (e.g., not associated with EBV)
  • One case report associated with HTLV-1 (Eur J Dermatol 2016;26:194)
  • Some cases that show progression to anaplastic large cell lymphoma show resistance to CD30 ligand and mutations of TGF-β (Semin Diagn Pathol 2017;34:22)
Clinical features
Diagnosis
Prognostic factors
Case reports
Treatment
Clinical images

Contributed by Roberto N. Miranda, M.D.

Sites of involvement

Dermoscopy evolution

Single nodular lesion 6 mm in diameter

Fully developed lesion with multiple papules in leg

Papule with central crust

Post inflammatory macule

Microscopic (histologic) description
  • Lymphomatoid papulosis is characterized by a wedge shaped pattern, with a wide superficial base and the tip at the bottom, usually deep dermis and less frequently into the subcutaneous tissue
  • The most characteristic appearance is the presence of few to numerous large cells with a Hodgkin or Hodgkin-Reed Sternberg admixed with a reactive background of small lymphocytes and less frequently eosinophils, plasma cells and histiocytes
  • The microscopic appearance and immunophenotype of large cells is variable and led to subclassification of lymphomatoid papulosis into different categories (J Am Acad Dermatol 2016;74:59, Blood 2019;133:1703, Semin Diagn Pathol 2017;34:22, J Am Acad Dermatol 2013;68:809, J Am Acad Dermatol 2012;66:928, Am J Clin Pathol 2003;119:731, Am J Surg Pathol 2010;34:1168, Am J Surg Pathol 2013;37:1)
    • Type A: wedge shaped and extensive lymphoid infiltrate with neutrophils, eosinophils and histiocytes; CD30+ cells are scattered and the overall histologic appearance mimics classic Hodgkin lymphoma
    • Type B: epidermotropism and band-like distribution of small to medium atypical lymphocytes with cerebriform nuclei, without CD30+ expression and mimics mycosis fungoides, patch stage
    • Type C: sheets of large cells, uniformly positive for CD30, with or without epidermotropism and few admixed inflammatory cells; the lesion mimics primary cutaneous anaplastic large cell lymphoma
    • Type D: atypical small to medium lymphoid infiltrate with epidermotropism; the neoplastic cells express CD30 and CD8 and mimic pagetoid reticulosis
    • Type E: angiocentric and angiodestructive pleomorphic lymphoid infiltrate of small to medium size lymphocytes; there are scattered large cells, positive for CD30 and the overall appearance is that of an aggressive lymphoma such as extranodal T/NK cell lymphoma, nasal type; EBER is negative
    • Lymphomatoid papulosis with DUSP22-IRF4 rearrangement: biphasic growth pattern with pagetoid reticulosis-like epidermotropism of small to medium size cerebriform lymphocytes that lack CD30; the second component is dermal or periadnexal and the atypical lymphocytes express CD30+
    • Rare forms
      • Folliculotropic: perifollicular infiltrate of atypical lymphocytes, cystic dilatation of hair follicle, rupture of hair follicle, hyperplasia of the follicular epithelium, intrafollicular pustules (neutrophil collections) and follicular mucinosis
      • Syringotropic: eccrine units with periglandular infiltrate
      • Granulomatous: mononuclear infiltrate with perivascular, eccrinotropic and neurotropic distribution associated with noncaseating granulomas
Microscopic (histologic) images

Contributed by Roberto N. Miranda, M.D.

Higher cellularity towards upper dermis

LyP type A with RS-like cells

LyP type A and CD30+

LyP type C

LyP type C with sheets of large cells


LyP type C and anaplastic morphology

LyP type C and CD3+

LyP type C and CD4+

LyP type C and CD8-

LyP type C and CD30+


LyP type C and TIA1+

LyP type E and angiocentricity

LyP type E and CD30+

LyP with DUSP22-IRF4 rearrangement

Positive stains
Negative stains
Immunohistochemistry
Immunohistochemical Summary of LyP Types
Type of LyP Reference CD2 CD3 CD4 CD5 CD7 CD8 CD30 Other markers
Type A Blood 2019;133:1703 +/- + + +/- +/- - + TIA1+
Type B Blood 2019;133:1703 +/- + + +/- +/- - - TIA1+
Type C Blood 2019;133:1703 +/- + + +/- +/- - + TIA1+
Type D Am J Surg Pathol 2010;34:1168 + + - - - + + TIA1+, βF1+, CD56-, EBER-
Type E Am J Surg Pathol 2013;37:1 + + -/+ + +/- + + CD45RA-, CD45RO+/-, TIA1+, βF1+, EBER-
LyP with DUSP22-IRF4 rearrangement Am J Surg Pathol 2013;37:1173 +/- + - +/- +/- +/- + CD15+, TIA1-, Ki67 (> 80%), TCR-β+
Folliculotropic LyP J Am Acad Dermatol 2013;68:809 + + + +/- - - +
Granulomatous LyP Am J Clin Pathol 2003;119:731 + + + + - - +
*All cases are anaplastic lymphoma kinase - 1 (ALK-1) negative
Molecular / cytogenetics description
  • Monoclonal rearrangement of the T cell receptor (TCR) is usually detected (Semin Diagn Pathol 2017;34:22)
  • Recurrent NPM-TYK2 gene fusion induces activation of STAT signaling pathway (Blood 2014;124:3768)
  • DUSP22-IRF4 rearrangement cases have characteristic features (Am J Surg Pathol 2013;37:1173)
    • 6p25.3 translocation
    • More common in older patients
    • Localized lesions and clinical presentation suggesting benign inflammatory dermatoses or epithelial tumors
    • Histologically has a bimodal pattern, with epidermotropic cells appearing small and uniform while dermal cells are large and CD30+
Sample pathology report
  • Skin of left ear, excisional biopsy:
    • CD30 positive T cell lymphoproliferative disorder, with extensive ulceration and necrosis, most consistent with lymphomatoid papulosis (see comment)
    • Comment: According to outside pathology report, the patient has a history of left ear abscess. No other clinical history is available at this time.
      One routinely stained slide shows four sections of squamous lined tissue with underlying lymphoid neoplasm and minimal remnants of skin that includes sebaceous glands and hair follicle. There is extensive ulceration and a dense diffuse infiltrate of large cells with vesicular nuclei, irregular nuclear outlines and occasional prominent nucleolus. Few mitotic figures are noted. Extensive coagulative necrosis, as well as suppurative necrosis is noted. Rare areas show perivascular viable cells surrounding by extensive necrosis.
      The immunohistochemical studies reveal the large neoplastic cells are positive for CD2, CD3, CD4, CD5, CD30 and a subset were positive for CD117 and TIA1. The aberrant cells are negative for CD10, CD20, ALK-1, PAX-5, cytokeratin, CD7, CD8, CD56, ALK and EBER.
      The features of this lesion are consistent with primary cutaneous CD30 positive T cell lymphoproliferative disorder, that encompasses lymphomatoid papulosis and cutaneous anaplastic large cell lymphoma. The final diagnosis of this relies on the clinical history. The differential diagnosis includes peripheral T cell lymphoma or ALK negative anaplastic large cell lymphoma with cutaneous involvement or transformation of mycosis fungoides. To exclude these possibilities, clinical correlation and staging studies are recommended.
Differential diagnosis

LyP Type A Primary cutaneous anaplastic large cell lymphoma
Reference Blood 2019;133:1703 Am J Dermatopathol 2017;39:877
Age Fifth decade Seventh decade
Gender (M:F) 2 - 3:1 2 - 3:1
Clinical Features Papular, papulonodular or nodular, < 2 cm Localized nodule or papule, usually > 2 cm
Microscopy Wedge shaped and large lymphoid infiltrate with neutrophils, eosinophils and histiocytes Diffuse and uniform dermal infiltrate of anaplastic large cells
Immunophenotype CD3+, CD4+, CD8-, CD30+ CD3+/-, CD4+, CD8-, CD30+
Treatment None for spontaneous regression; symptomatic treatment for relief Excision, radiation or chemotherapy, alone or combined
Outcomes Excellent Excellent

LyP Type B Early stage mycosis fungoides
Reference Blood 2019;133:1703 An Bras Dermatol 2018\;93:546
Age Fifth decade Sixth decade
Gender (M:F) 2 - 3:1 5:4
Clinical Features Papular, papulonodular or nodular Patches and plaques
Microscopy Epidermotropism and band-like distribution of small / medium atypical lymphocytes with cerebriform nuclei (MF-like) Cerebriform cells with epidermotropism, predominate along basal layer of epidermis
Immunophenotype CD4+, CD8-, CD30- CD4+, CD7-, CD8-, CD30-
Treatment Spontaneous regression or symptomatic treatment Ultraviolet light
Outcomes Excellent Good

LyP Type C Primary cutaneous anaplastic large cell lymphoma
Reference Blood 2019;133:1703 Am J Dermatopathol 2017;39:877
Age Fifth decade Seventh decade
Gender (M:F) 2 - 3:1 2 - 3:1
Clinical Features Papular, papulonodular or nodular; < 2 cm Localized nodule or papule, > 2 cm
Microscopy Sheets of large lymphocytes with or without epidermotropism and few admixed inflammatory cells Diffuse dermal infiltrate of anaplastic morphology
Immunophenotype CD4+, CD8-, CD30+ (uneven) CD3+/-, CD4+, CD8-, CD30+ (uniform)
Treatment Spontaneous regression or symptomatic treatment Radiation or chemotherapy, alone or combined
Outcomes Excellent Good

LyP Type D Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma
Reference Am J Surg Pathol 2010;34:1168 Mod Pathol 2017;30:761
Age Third decade Fourth decade
Gender (M:F) 6:3 5:2
Clinical Features Papules and small nodules Ulcerative patches or plaques
Microscopy Epidermotropism with pagetoid reticulosis-like Small to intermediate size lymphocytes with epidermotropism
Immunophenotype CD2+, CD3+, CD4-, CD8+, CD30+, TIA1+ CD2-, CD3+, CD7+, CD8+, CD30-, CD56-
Treatment Spontaneous regression or symptomatic treatment Chemotherapy, stem cell transplant
Outcomes Excellent Poor

LyP Type E Extranodal NK/T cell lymphoma, nasal type
Reference Am J Surg Pathol 2013;37:1 Blood 2019;133:1703, Curr Hematol Malig Rep 2016;11:514
Age Sixth decade Fifth and sixth decade
Gender (M:F) 3:1 2:1
Clinical Features Recurrent papular lesions with rapid progression to hemorrhagic necrotic ulcers Necrotic lesions
Microscopy Angiocentric and angiodestructive pleomorphic lymphoid infiltrate of small / medium size Atypical lymphocytes; angiocentric and angiodestructive in most cases
Immunophenotype CD2+, CD3+, CD4-/+, CD8+, CD30+, TIA1+ CD3-, CD4-, CD5-, CD8-, CD30+, CD56+, TIA1+, EBER+
Treatment Spontaneous regression or symptomatic treatment Progressive disease
Outcomes Excellent Poor

LyP with DUSP22-IRF4 rearrangement Transformed mycosis fungoides
Reference Am J Surg Pathol 2013;37:1173 Pathology 2014;46:610
Age Eighth decade Seventh decade
Gender (M:F) 9:2 1.1:1
Clinical Features One or multiple eruptive and papulonodular lesions in a single body area Patches, plaques and tumor
Microscopy Biphasic growth pattern and epidermotropism and periadnexal small to medium size cerebriform cells Cerebriform with increased large cells in dermis
Immunophenotype CD3+, CD4-, CD8+/- CD3+, CD4-, CD7-, CD8-, CD30+/-
Treatment Spontaneous regression or symptomatic treatment Radiation, chemotherapy
Outcomes Excellent Poor

Folliculotropic LyP Folliculitis
Reference J Am Acad Dermatol 2013;68:809 Folliculitis
Age Sixth decade Variable
Gender (M:F) 9:2 Variable
Clinical Features Follicular pustules Superficial folliculitis
Microscopy Perifollicular infiltrate of atypical lymphocytes and follicular mucinosis Moderate mixed inflammatory cells in the follicular ostium
Immunophenotype CD3+, CD4+, CD30+ Nonclonal
Treatment Spontaneous regression Topical treatment
Outcomes Excellent Excellent

Granulomatous LyP Discoid lupus erythematous
Reference Am J Clin Pathol 2003;119:731 Arch Dermatol 2009;145:249
Age Fifth decade Fifth decade
Gender (M:F) 5:4 1:2
Clinical Features Nodules Discoid lesions
Microscopy Noncaseating granulomas associated with mononuclear infiltrate with perivascular, eccrinotropic and neurotropic distribution Edema and a mild infiltrate of inflammatory cells (lymphocytes) in upper dermis
Immunophenotype CD3+, CD4+, CD5-, CD7-, CD8-, CD30+ CD3+, CD4+; no loss of T cell antigens
Treatment Spontaneous regression Systemic agents, Phototherapy
Outcomes Excellent Excellent
Board review style question #1
Which is the rearrangement that defines a type of lymphomatoid papulosis?

  1. ETV6-ABL
  2. EML4-ALK
  3. DUSP22-IRF4
  4. NPM-TYK2
Board review answer #1
C. DUSP22-IRF4

Reference: Lymphomatoid papulosis

Comment here
Board review style question #2
Which LyP types are usually associated with a cytotoxic phenotype?

  1. Type A and B
  2. Type B and C
  3. Type C and D
  4. Type D and E
Board review answer #2
D. Type D and E

Reference: Lymphomatoid papulosis

Comment here
Back to top
Image 01 Image 02