Case 3 -

Pseudoepitheliomatous Hyperplasia Mimicking Squamous Cell Carcinoma in Association with a CD30+ Lymphoproliferative Disorder Dr E. Jaime Calonje St John's Institute of Dermatology St Thomas' Hospital, London, UK

Clinical history Male, 77 years old. The patient presented with an eight week history of a rapidly enlarging, non-painful, ulcerated, nodule on left side of abdomen. Initially was the size of a pea. No response to treatment with antibiotics and topical steroids. No purulent discharge but bleeding after trauma. On examination, there was a 2 x 2 cm friable, fleshy, mobile, ulcerated crusted nodule with surrounding erythema on left abdomen. No other cutaneous lesions were found and there was no lymphadenopathy. Clinical diagnosis: ?Keratoacanthoma. ?Squamous cell carcinoma. Further investigation after biopsy. Normal full blood count, renal function tests and live function tests. CT scan of the trunk and pelvis: anterior small mediastinal lymph node and a small pre-carinal lymph node. Case 3 - Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histopathology Ulcerated nodule with a squamoproliferative lesion associated with the epidermis and the infundibular portion of the hair follicles. In the surrounding dermis there is a prominent, fairly polymorphic infiltrate. In the epidermis and hair follicles there are strands and lobules of pale keratinocytes with an endophytic growth pattern and focal keratinisation. The keratinocytes in the proliferation are fairly homogenous with some degree of cytological atypia that tends to be mild. The lobules and strands of squamous epithelium appear to be infiltrating the dermis. In areas, some nests of keratinocytes display cystic change and there is exocytosis of neutrophils with formation of microabscesses. The infiltrate around the squamous proliferation is dense and consists of neutrophils, eosinophils, mature round lymphocytes and sheets of large atypical lymphoid cells with hyperchromatic nuclei, one or more nucleoli and pink cytoplasm. Immunohistochemical stains reveal the following phenotype in the large dermal lymphoid cells: CD2, CD3, CD4 & CD5: positive. CD7: Focal loss of expression. CD30: Diffuse cytoplasmic and dot-like perinuclear positivity. EMA and ALK-1: negative. Diagnosis Pseudoepitheliomatous hyperplasia mimicking squamous cell carcinoma in association with a CD30+ lymphoproliferative disorder (CD30 positive anaplastic large cell lymphoma) Primary cutaneous anaplastic large cell lymphoma Adults 7th decade M:F 2-3:1 Solitary or localised nodules/tumours Multifocal lesions ~20% Extracutaneous dissemination to regional lymph nodes ~10% No preceding LyP, MF or other CTCL 75% or more of the cells in the infiltrate are CD30+ cells Immunophenotype: usually CD4+ T-cell phenotype Most cases are ALK-1 negative (absence of t(2;5) translocation ALK-1 +ve: usually indicates cutaneous involvement by systemic disease In systemic cases EMA tends to be positive in tumour cells Prognosis of primary cutaneous CD30 positive anaplastic large cell lymphoma: 5 year survival >90% Management: Excision/radiotherapy/chemotherapy Lymphomatoid papulosis Now regarded as a CD30 positive lymphoproliferative disease Chronic, self healing 4-5th decade, rarely children M:F 1.5:1 Trunk, limbs Crops of necrotic papules or nodules 3-12 weeks to emerge Atrophic scarring 20% associated with another type of lymphoma (cutaneous T cell lymphoma, Hodgkin's disease) Three histological types of lymphomatoid papulosis have been described: LyP type A: (80% of cases): clusters of large CD30+ anaplastic cells with reactive lymphocytes, neutrophils and/or eosinophils in the background. LyP type B: (10% of cases): shows an epidermotropic infiltrate, has few CD30 positive cells and mimics cutaneous T cell lymphoma. LyP type C: (10% of cases): shows a monotonous population of large CD30+ in sheets. Distinction between CD30 positive anaplastic large cell lymphoma and LyP can only be made based on very close clinicopathological correlation. Pseudoepitheliomatous hyperplasia may be seen in 28-55% of CD30+ anaplastic large cell lymphomas and in a smaller percentage of cases of lymphomatoidc papulosis. The degree of hyperplasia is variable but may be quite prominent as to closely mimic a squamous cell carcinoma. This is particularly true in large lesions of anaplastic large cell lymphoma. In patients that present with multiple lesions of anaplastic large cell lymphoma, the differential diagnosis in cases with pseudoepitheliomatous hyperplasia is not difficult. The main problem arises in patients presenting with a single tumour like in our case. The problem may be further compounded by the fact that many clinicians tend to perform very small diagnostic biopsies nowadays. If the biopsy is too superficial and if particular attention is not paid to the dermal infiltrate, this may result in a misdiagnosis of squamous cell carcinoma and the therapeutic approach will be wrong. It is also always important, particularly in the case of small samples to play very close attention to the clinical information. Cutaneous squamous cell carcinomas almost always occur in the background of sun-damaged skin in elderly patients. If a diagnosis of a cutaneous squamous cell carcinoma is been considered in a small sample from a site not displaying sun damage, it may be crucial to defer the diagnosis and to request a further larger specimen. This not only applies to pseudoepitheliomatous arising in large cell anaplastic lymphoma but to other conditions associated with this change. The presence of large number of dermal atypical lymphoid cells in the background of pseudepitheliomatous hyperplasia allows easy distinction from other diseases presenting with pseudoepitheliomatous hyperplasia listed below. Differential diagnosis (Pseudoepitheliomatous hyperplasia) Chronic venous ulceration Infections (including deep fungal infections, botryomycosis, atypical mycobacteria, verrucous tuberculosis) Hypertrophic lichen planus Orf Halogenodermas (iododerma and bromoderma) Superficial granulomatous pyoderma (a superficial variant of pyoderma gangrenosum) Blastomycosis-like pyoderma Basal cell carcinoma Melanocytic naevi Melanoma Granular cell tumour CD30 + lymphoproliferative disorders (CD30+ Anaplastic Large Cell Lymphoma/ Lymphomatoid papulosis) Mycosis fungoides References Guitart J, Gordon K. Keratoacanthomas and lymphomatoid papulosis. Am J Dermatopathol 1998; 20: 430-433. Courville, P, Wechsler J, Thomine E, Vergier B, Fonck Y, Souteyrand P, Beylot-Barry M, Bagot M, Joly P. 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: 421-426. Scarisbrick JJ, Calonje E, Orchard G, Child FJ, Russell-Jones R. Pseudocarcinomatous change in lymphomatoid papulosis and primary cutaneous CD30+ lymphoma: a clinicopathologic and immunohistochemical study of 6 patients. J Am Acad Dermatol 2001; 44: 239-247. Tronnier M, Merz H. Anaplastic large cell lymphoma and keratoacanthoma. Hautarzt 200; 55: 182-185.