2016 AAD SUMMER MEETING SYMPOSIUM S011: CLINICOPATHOLOGIC SELF-ASSESSMENT 7/30/16 2:00 PM. Tom Helm, MD

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1 2016 AAD SUMMER MEETING SYMPOSIUM S011: CLINICOPATHOLOGIC SELF-ASSESSMENT 7/30/16 2:00 PM Tom Helm, MD Case 1 Diagnosis: Pseudoepitheliomatous hyperplasia associated with CD30+ lymphoproliferative disease Histology: Irregular proliferation of the epidermis Keratinocytes with glassy cytoplasm Atypical lymphocytes intimately associated with the epidermal proliferation Case History: This 57 year old woman presented for evaluation of multiple keratotic nodules. Biopsy revealed irregular acanthosis of the epidermis and an infiltrate of atypical lymphoid cells in the dermis. Gene rearrangement studies confirmed the presence of monoclonal lymphocytes. CD30 and CD3 stains confirmed that the large and atypical neoplastic cells were T lymphocytes. A cytokeratin stain highlighted the associated irregular proliferation of keratinocytes. Simple excision of multiple nodules revealed varying degrees of epidermal hyperplasia and pseudoepitheliomatous hyperplasia associated with the atypical lymphoid infiltrate. None of the lesions recurred after simple excision, and lesions improved with treatment of the underlying lymphoproliferative disorder. Discussion: The concepts associated with CD30+ lymphoproliferative disease have expanded greatly since the first description of lymphomatoid papulosis in Anaplastic large cell lymphoma was originally described as regressing atypical histiocytosis, but molecular testing and immunohistochemical marker

2 studies coupled with sophisticated genomic evaluation have revealed that CD30+ lymphoproliferative disease represents a spectrum of disease extending from localized indolent disease to aggressive lymphoma. Differences in underlying genetic abnormalities and host response are thought to be important determinants in shaping the ultimate phenotypic expression of an individual patient s disease. Reports of CD30+ lymphoproliferative disease now include clinical presentations such as the classic and typical clustered lesions of lymphomatoid papulosis, solitary ulcerated tumors, angioinvasive lesions, presentations associated with mycosis fungoides as well as many other clinical presentations. Pseudoepitheliomatous hyperplasia is still fairly uncommonly encountered in the setting of cutaneous lymphoma and lymphoproliferative disease, but is increasingly recognized as one of many possible presentations, especially in lymphomas associated with a prominent infiltrate of neutrophils and eosinophils. Cytokines EGF, TGF-alpha, and IL-5 are thought to play a role in the development of the epithelial hyperplasia in such cases. Researchers have suggested that CD30+ lymphoid cells may prevent CD95 combining with the CD95 receptor, which disrupts apoptotic homeostatic mechanisms of keratinocyte growth. CD30+ lymphoid cells may also directly secrete growth factors that lead to keratinocyte proliferation. Th17/Th22 cytokines may be involved as well as interferon gamma-induced proinflammatory cytokines produced by keratinocytes. A recent poster at the 2014 ASDP meeting catalogued the distinct reported subtypes of lymphomatoid papulosis (Table I). These types include the most common presentation with a mixed infiltrate including transformed lymphocytes in the dermis, a mycosis-fungoides-like epidermotropic pattern, sheets of transformed cells mimicking aggressive lymphoma, a cytotoxic phenotype, and angioinvasive pattern, and a biphasic pattern associated with a 6p25.3 chromosomal rearrangement. Although the keratinocytic proliferation in cases such as this may closely mimic squamous cell carcinoma in some instances, lesions respond well to simple excision. The underlying lymphoid infiltrate seems to be the driving force associated with the epidermal changes. If you are aware of a case where the keratinocytic/epidermal component of such a lesion is associated with an aggressive clinical course, I would be very interested in learning about your case.

3 Table I (from Bax M et al. Pseudoepitheliomatous hyperplasia associated with CD30+ lymphoproliferative disease. A potential mimic of squamous cell carcinoma. Poster presentation at the American Society of Dermatopathology Annual Meeting. 2014) : Type A Type B Type C Type D Type E Type F Type G Type H Mixed dermal infiltrate of large transformed lymphocytes associated with neutrophils and eosinophils Predominance of epidermotropic intraepidermal lymphocytes with a mycosis fungoides-like pattern Sheets of atypical lymphocytes in the dermis with variable epidermotropism Epidermotropic cytotoxic CD8+ phenotype Ulcerative angioinvasive and oligolesional LyP Biphasic pattern with smaller lymphocytes in the epidermis, larger atypical lymphocytes in the dermis, and chromosomal rearrangement of the DUSP22- IRF4 locus on 6p25.3 Prominent pseudoepitheliomatous hyperplasia mimicking squamous cell carcinoma Pityriasis lichenoides et varioliformis acuta like presentation of lymphomatoid papulosis References: 1. Macaulay WL. Lymphomatoid papulosis: A continuing self-healing eruption, clinically benignhistologically malignant. Arch Dermatol. 1968; 97: Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol. 1993; 28: El Shabrawi-Caelen L, Kerl H, Cerroni L. Lymphomatoid papulosis: reappraisal of clinicopathologic presentation and classification into subtypes A, B, and C. Arch Dermatol. 2004; 140: Saggini A, Gulia A, Argenyi Z et al. A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases. Am J Surg Pathol. 2010; 34: Magro CM, Crowson AN, Morrison C et al. CD8+ lymphomatoid papulosis and its differential diagnosis. Am J Clin Pathol. 2006; 125:

4 6. Kempf W, Kazakov DV, Scharer L et al. Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas. Am J Surg Pathol. 2013; 37: Karai LJ, Kadin ME, Hsi ED, Sluzevich JC, Ketterling RP, Knudson RA, Feldman AL. Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am J Surg Pathol. 2013; 37: Lin JH, Lee JY. Primary cutaneous CD30+ anaplastic large cell lymphoma with keratoacanthoma-like pseudocarcinomatous hyperplasia and marked eosinophilia and neutrophilia. J Cutan Pathol. 2004; 31: Valiathan M, Rao RV, Rao L et al. Nasal NK/T cell lymphoma mimicking a squamous cell carcinoma: a case report. Indian J Pathol Microbiol. 2005; 48: Zayour M, Gilmore E, Heald P et al. A distinct entity in the spectrum of the CD30+ cutaneous lymphoproliferative diseases: oligolesional nodules with pseudoepitheliomatous hyperplasia followed by spontaneous resolution. Am J Dermatopathol. 2009; 31: Courville P, Wechsler J, Thomine E et al. Pseudoepitheliomatous hyperplasia in cutaneous T-cell lymphoma. A clinical, histopathological and immunohistochemical study with particular interest in epithelial growth factor expression. The French Study Group on Cutaneous Lymphoma. Br J Dermatol. 1999; 140: Bernier M, Bagot M, Broyer M et al. Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases. J Cutan Pathol. 1997; 24: Cespedes YP, Rockley PF, Flores F et al. Is there is a special relationship between CD30 positive lymphoproliferative disorders and epidermal proliferation? J Cutan Pathol. 2000; 27: Scarisbrick JJ, Calonje E, Orchard G et al. Pseudocarcinomatous change in lymphomatoid papulosis and primary cutaneous CD30+ lymphoma: a clinicopathologic and immunohistochemical study of 6 patients. J Am Acad Dermatol. 2001; 44: Sugiyama H, Asagoe K, Morizane S et al. Leukocyte common antigen-negative, aggressive cutaneous anaplastic large cell lymphoma with prominent pseudocarcinomatous hyperplasia. Eur J Dermatol. 2008; 18: Resnik KS, Kutzner H. Mimicry illuminating pitfalls in histopathologic diagnosis: nutritional deficiency-like dermatitis secondary to topical tazarotene and keratoacanthomatous pseudocarcinomatous hyperplasia in CD30+ lymphoproliferative disorder as illustrative. Am J Dermatopathol. 2009; 31: Kempf W, Kazakov DV, Palmedo G, Fraitag S et al. Pityriasis lichenoides et varioliformis acuta with numerous CD30+ cells: a variant mimicking lymphomatoid papulosis and other cutaneous lymphomas. A clinicopathologic, immunohistochemical, and molecular biological study of 13 cases. Am J Surg Pathol. 2012; 36: Xiong J, Ma Y, Chen H, Xu X, Sun J. Lymphomatoid papulosis with pseudocarcinomatous hyperplasia in a 7-year-old girl: a case report. J Cutan Pathol. 2016; 43 (5):

5 19. Guitart J, Martinez-Escala ME, Deonizio JM, Gerami P, Kadin MI. CD30+ cutaneous lymphoproliferative disorders with pseudocarcinomatous hyperplasia are associated with a T- helper-17 cytokine profile and infiltrating granulocytes. J Am Acad of Dermatol. 2015; 72: Bax MJ, Helm MA, Conroy DR, Grassi M. Pseudoepitheliomatous hyperplasia associated with CD30+ lymphoproliferative disease. A potential mimic of squamous cell carcinoma. Poster presentation at the American Society of Dermatopathology Annual Meeting, 2014.

6 Case 2 Diagnosis: Zosteriform lichenoid eruption post herpes zoster Clinical History: A 56-year-old woman had a persistent eruption on the right postero-lateral thigh. Histology: Lichenoid inflammation Necrotic keratinocytes Superficial and deep infiltrate Discussion: The histologic findings in this case raise a broad differential diagnosis that include a variety of lichenoid dermatoses including a drug eruption, a lichenoid lesion of graft vs. host disease, lupus erythematosus, lichen planus, as well as other lichenoid eruptions. The clinical images reveal a dermatomal distribution of lesions rather than lesions confined to Blaschko s lines. Viral cytopathic effect is not identified. Careful history revealed that the quality of the eruption had changed. The patient had discomfort before a vesicular and erosive eruption developed, and later developed pruritic lichenoid papules. The clinical and histologic information best supports a diagnosis of a lichenoid eruption occurring after herpes zoster infection. How herpes zoster elicits some of the unusual vascular, granulomatous, or lichenoid sequelas in affected dermatomes is unclear. Some investigators have indicated that the cutaneous reactions appearing in areas affected by herpes zoster are not due to the persistence of varicella-zoster virus DNA within the lesions but rather persistence of viral envelope glycoproteins, but this is still an area of active study.

7 References: 1. Lora V, Cota C, Kanitakis J. Zosteriform lichen planus after herpes zoster: report of a new case of Wolf s isotopic phenomenon and literature review. Dermatol Online J Nov; 20 (11): Ruocco V, Ruocco E, Ghersetich I, Bianchi B, Lotti T. Isotopic response after herpesvirus infection: an update. J Am Acad Dermatol. 2002; 46 (1): Requena L, Kutzner H, Escalonilla P, Ortiz S, Schaller J, Rohwedder A. Cutaneous reactions at sites of herpes zoster scars: an expanded spectrum. Br J Dermatol. 1998; 138 (1): Gianotti R, Restano L, Grimalt R, Briti E, Alessi E, Caputo R. Lichen striatus a chameleon: a histopathological and immunohistological study of forty-one cases. J Cutan Pathol. 1995; 22 (1): Hofer T. Lichen striatus in adults or adult blaschkitis? There is no need for a new naming. Dermatology. 2003; 07 (1): Lee DY, Kim S, Kim CR, Kim HJ, Byun JY, Yang JM. Lichen striatus in an adult treated by a short course of low-dose systemic corticosteroid. J Dermatol. 2011; 38 (3): Taieb A et al. Lichen striatus; a Blaschko linear acquired inflammatory skin eruption. Journal of the American Academy of Dermatology. 1991;25: Ferenczi K, Rosenberg AS, McCalmont TH, Kwon EJ, Elenitsas R, Somach SC. Herpes zoster granulomatous dermatitis: histopathologic findings in a case series. J Cutan Pathol 2015; 42: