Lymphomatoid Papulosis

C. Cameron Yin, MD, PhD

Key Facts

Terminology

Chronic, self-healing and recurrent erythematous papules/nodules on skin of trunk and extremities

Clinical Issues

Usually remains confined to skin
Excellent prognosis

Microscopic Pathology

4 histologic types represent a spectrum of disease
Type A is most common
- Scattered large atypical Reed-Sternberg-like cells
- Numerous inflammatory cells including small lymphocytes, histiocytes, granulocytes
Type B is uncommon (< 10%)
- Epidermotropism and band-like dermal infiltrate
- Lymphoid cells with cerebriform nuclei
Type C
- Clusters or sheets of large atypical lymphoid cells with relatively few admixed inflammatory cells
Type D
- Epidermotropism; CD8(+)

Ancillary Tests

Large atypical cells are CD30(+)
Small lymphocytes are T cells: Usually CD7(-)

Top Differential Diagnoses

Primary cutaneous ALCL
Systemic ALCL with cutaneous involvement
Classical Hodgkin lymphoma

Reporting Considerations

In many cases, LyP cannot be distinguished from C-ALCL without clinical information/follow-up

Lymphomatoid papulosis (LyP), type C. A dense lymphoid infiltrate fills the dermis and is composed of medium to large atypical cells with frequent mitoses

. This lesion spontaneously regressed.

Immunohistochemical study for CD30 in a case of LyP type C. Strong and uniform CD30(+) is characteristic of LyP and sheets of CD30(+) cells support type C. This lesion spontaneously regressed.

TERMINOLOGY

Abbreviations

Lymphomatoid papulosis (LyP)

Synonyms

Primary cutaneous CD30(+) T-cell lymphoproliferative disorder
- This term also includes cutaneous anaplastic large cell lymphoma (C-ALCL)

Definitions

Chronic, self-healing and recurrent skin lesions characterized by erythematous papules/nodules on trunk and extremities
Composed of large atypical cells in marked inflammatory background
Initially described by Macaulay as “a continuing self-healing eruption, clinically benign, histologically malignant”

ETIOLOGY/PATHOGENESIS

Unknown

Suggested factors
- Viral infection, reduced immunosurveillance
- Chronic antigenic stimulation, direct oncogenic effect of immunosuppressive drugs
Outbreaks may be triggered by stress or illness
TNFR-associated factor-1 and cutaneous lymphocyte antigen (E-selectin ligand) are highly expressed in LyP

CLINICAL ISSUES

Epidemiology

Age
- Median: 45 years (wide age range, including children)
Gender
- Male to female ratio = 2-3:1

Site

Trunk and extremities most common
Genital and oral mucosa can be rarely involved

Presentation

Papular, papulonodular, or nodular skin lesions at different stages of development
- Clusters or disseminated; ± ulceration
Individual skin lesions spontaneously regress within 3-12 weeks
- After resolution, superficial scars can remain; hypo-or hyperpigmented
Waxing and waning clinical course; can persist for decades
LyP usually remains confined to skin
- Can disseminate to regional lymph nodes
- Very rarely disseminates elsewhere

Treatment

No specific therapy for most patients; follow-up with attention to skin lesion changes or development of lymphadenopathy
Therapy options include
- Surgical removal ± irradiation or low-dose methotrexate for skin-restricted disease
- Multiagent chemotherapy for extracutaneous lesions

Prognosis

Excellent
- 10-year disease-specific survival of ˜ 100%
Spontaneous regression in > 40% of patients
10-20% of patients develop a 2nd lymphoma
- Mycosis fungoides (MF), C-ALCL, or classical Hodgkin lymphoma
LyP patients have increased risk for nonlymphoid cancers

MICROSCOPIC PATHOLOGY

Histologic Features

Typically wedge-shaped lesion involving dermis
Epidermis is usually sparsely infiltrated and often ulcerated
4 histologic types have been recognized, which represent a spectrum of disease
- Arbitrarily designated as A, B, C, and D
Type A is most common
- Scattered large atypical Reed-Sternberg-like cells
- Numerous inflammatory cells including small lymphocytes, histiocytes, neutrophils, and eosinophils
Type B is uncommon (< 10%)
- Simulates MF with epidermotropism and band-like dermal infiltrate
  - Composed of small to medium-sized lymphoid cells with cerebriform nuclei
  - Cannot be distinguished from MF by histology or immunophenotyping alone
  - Unlike MF, type B LyP usually regresses spontaneously
Type C
- Large clusters or sheets of large atypical lymphoid cells with relatively few admixed inflammatory cells
- Cannot be distinguished from C-ALCL by histology or immunophenotyping alone
- Type C LyP is smaller (usually < 10 mm) than C-ALCL and spontaneously regresses over time
Type D has been recently described
- Characterized by marked epidermotropism and CD8(+)

ANCILLARY TESTS

Immunohistochemistry

Types A and C
- Large atypical cells are CD30(+), ALK(-)
- Small lymphocytes are T cells
  - CD2(+), CD3(+), CD5(+), CD7 often (-); CD4(+), CD8(-)
- Frequent expression of cytotoxic proteins: TIA-1, granzyme B, &/or perforin
Type B: Small cells with cerebriform nuclei are CD3(+), CD4(+), CD8(-), CD30(-)
- Occasionally LyP has CD8(+) immunophenotype
  - More common in children
Type D: Atypical lymphocytes are CD30(+), CD3(+), CD4(-), CD8(+)