FINAL DIAGNOSIS: GRANULOMATOUS ECCRINOTROPIC LYMPHOMATOID PAPULOSIS.
The skin punch biopsy H&E-stained sections show dense lymphohistiocytic infiltrate in the deep dermis. The infiltrate, largely nonepitheliotropic, is a nodular lymphocytic infiltrate manifesting accentuation around the eccrine coil accompaning by variable histiocytic inflammation. Scattered large lymphoid cells are intermingled with numerous small lymphocytes mixed with occasional neutrophils and eosinophils. There is also a component of superficial and deep perivascular infiltrate. The overlying epidermis shows focal parakeratosis. Immunohistochemical stains show predominantly T cells with just few B cells present. The infiltrate reveals positivity for CD3, CD4, scattered CD8, CD5, CD7 and CD43. Large cells are CD3+, CD4+ and CD30+. Number of CD56+ cells are increased which are also positive for TIA and Granzyme B. No cells are positive for ALK1. Polymerase chain reaction (PCR) studies reveal clonal rearrangement of the T-cell receptor (TCR).
Primary cutaneous CD30+ lymphoproliferative disorders (LPDs) are the second most common group of cutaneous T-cell lymphomas (CTCLs), accounting for approximately 30% of CTCLs. This group includes primary cutaneous anaplastic large cell lymphoma (C-ALCL), lymphomatoid papulosis (LyP), and borderline cases. It is now generally accepted that C-ALCL and LyP form a spectrum of disease, and that histologic criteria alone are often insufficient to differentiate between these 2 ends of this spectrum. The clinical appearance and course are used as decisive criteria for the definite diagnosis and choice of treatment. The term "borderline case" refers to cases in which, despite careful clinicopathologic correlation, a definite distinction between C-ALCL and LyP cannot be made. Clinical examination during further follow-up will generally disclose whether the patient has C-ALCL or LyP.
Definition: Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease with histologic features suggestive of a (CD30+) malignant lymphoma.
Clinical features: LyP generally occurs in adults (median age, 45 years; male-to-female ratio, 1.5:1), but may occur in children as well. LyP is characterized by the presence of papular, papulonecrotic, and/or nodular skin lesions at different stages of development, predominantly on the trunk and limbs. Individual skin lesions disappear within 3 to 12 weeks, and may leave behind superficial scars. The duration of the disease may vary from several months to more than 40 years. In up to 20% of patients LyP may be preceded by, associated with, or followed by another type of malignant (cutaneous) lymphoma, generally mycosis fungoides (MF), a (C-)ALCL, or Hodgkin lymphoma. In some cases, molecular studies suggest an evolution of lesions of LyP into mycosis fungoides or primary cutaneous CD30+ ALCL rather than the secondary lymphoma being a genomically independent event. Several months later, this patient developed T-cell lymphoma consistent with MF with lymph node involvement. The PCR bands seen on skin lesion corresponded to the bands seen on lymph node specimen.
Histopathology: The histologic picture of LyP is extremely variable, and in part correlates with the age of the biopsied skin lesion. Three histologic subtypes of LyP (types A, B, and C) have been described, which represent a spectrum with overlapping features. In LyP type A lesions, scattered or small clusters of large, sometimes multinucleated or Reed-Sternberg-like, CD30+ cells are intermingled with numerous inflammatory cells, such as histiocytes, small lymphocytes, neutrophils, and/or eosinophils. LyP type C lesions demonstrate a monotonous population or large clusters of large CD30+ T cells with relatively few admixed inflammatory cells. LyP type B is uncommon (less than 10%) and is characterized by an epidermotropic infiltrate of small atypical cells with cerebriform nuclei similar to that observed in MF. This patient infiltrate is most consistent with a type A LyP.
The standard descriptions of LyP emphasize wedgeshaped infiltrates manifesting angiocentricity, a polymorphous inflammatory background and lymphocytic migration into the epidermis. The skin infiltrate in this case was predominantly eccrinotropic with minimal exocytosis. Recognition of this variant is important owing to potential diagnostic confusion with other entities. A.N. Crowson et al. encountered 9 cases of LyP in which nonepitheliotropic, deep-seated nodular foci of eccrinotropic and neurotropic inflammation were accompanied by variable granulomatous and small lymphocytic components. All cases posed difficulties in clinical and pathologic diagnosis and raised consideration of neurotropic infections such as herpes or syphilis, arthropod bite reactions, lymphocytoma or lymphoma cutis, Jessner lymphocytic infiltrate of skin, and chronic discoid lupus erythematosus. They proposed the term granulomatous eccrinotropic lymphomatoid papulosis for this distinctive morphologic pattern that had not been emphasized previously in descriptions of LyP. N. Kato et al. Reported a case of LyP with lesions that were accentuated around the hair follicles.
Immunophenotype: The large atypical cells in the LyP type A and type C lesions have the same phenotype as the tumor cells in C-ALCL (CD30+/CD3+/CD4+). The atypical cells with cerebriform nuclei in the LyP type B lesions have a CD3+, CD4+, CD8- phenotype and do not express CD30 antigen.
Genetic features: Clonally rearranged T-cell receptor genes have been detected in approximately 60%-70% of LyP lesions. Identical rearrangements have been demonstrated in LyP lesions and associated lymphomas. The (2;5)(p23;q35) translocation is not detected in LyP.
Prognosis and predictive factors: LyP has an excellent prognosis. In a recent study of 118 LyP patients only 5 (4%) patients developed a systemic lymphoma, and only 2 (2%) patients died of systemic disease over a median follow-up period of 77 months. Risk factors for the development of a systemic lymphoma are unknown.
Treatment: Since a curative therapy is not available and none of the available treatment modalities affects the natural course of the disease, the short-term benefits of active treatment should be balanced carefully against the potential side effects. Low-dose oral methotrexate (5-20 mg/wk) is the most effective therapy to suppress the development of new skin lesions. Beneficial effects have been reported of PUVA and topical chemotherapy. However, after discontinuation of treatment the disease generally relapses within weeks or months. Therefore, in patients with relatively few and nonscarring lesions, long-term follow-up without active treatment should be considered.
Contributed by Franklin Sedarat, MD, MSc and Drazen Jukic, MD, PhD