Ashraf M. Hassanein

β-Catenin is expressed aberrantly in tumors expressing shadow cells: Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst

We studied the beta-catenin immunohistochemical profile in tumors expressing shadow cells: pilomatricoma, 10 cases; calcifying odontogenic cyst, 6 cases; and craniopharyngioma, 9 cases. There was strong membranous, cytoplasmic, and nuclear staining of the immature basaloid cells in all of these tumors. Shadow cells were negative in all tumors. It has been documented that rising levels of free beta-catenin drive the formation of complexes with T-cell factor/lymphoid enhancer factor (TCF-Lef) and up-regulate the wingless-Wnt cell-cell signals. The end result is an abnormality of beta-catenin degradation and, thus, a buildup of free beta-catenin in the cytoplasm and/or nucleus, resulting in the stimulation of cellular proliferation and/or inhibition of cell death. beta-Catenin seems to have an important role in the oncogenesis of these tumors. The similar pattern of keratinization in these tumors and the similar pattern of beta-catenin immunoreactivity in the cytoplasm and the nucleus are important findings. It seems that the activation of a common cellular pathway, namely Wnt-beta-catenin-TCF-Lef, has a role in the pathogenesis of these tumors. The latter could be related to their shared method of keratinization or shared dysfunction of the cellular adhesion complex leading to tumorigenesis.

Nephrogenic fibrosing dermopathy in pediatric patients

Nephrogenic fibrosing dermopathy (NFD) is a rare and recently recognized sclerosing skin disorder of unknown etiology. Reported cases have occurred in patients with chronic renal failure, with or without renal replacement therapy. All previous cases have been reported in older adult patients. We describe two pediatric patients who recently developed this condition and review the existing literature for NFD. Our patients included an 8-year-old boy on peritoneal dialysis with no prior renal transplant and a 19-year-old boy on hemodialysis with a history of previous failed renal transplants. We speculate that the recent emergence of this condition and occurrence in patients with chronic renal failure suggest an association with some newer pharmacological agent that has recently come into wide use. Since both our patients also had previously experienced large vessel thrombosis, hypercoagulable states may also be implicated.

Acral myxoinflammatory fibroblastic sarcomas: are they all low-grade neoplasms?

Acral myxoinflammatory fibroblastic sarcoma (AMIFS) is a low‐grade sarcoma that presents mostly in distal extremities of middle‐aged patients. The clinicopathologic features, immunohistochemical profile and follow‐up data of five cases (three men and two women; age 39–65 years) are presented. The tumors presented as a slow‐growing, poorly circumscribed, subcutaneous masses in the hands (three), foot (one) and calf (one), with dermal involvement in two cases. They had myxoid and hyaline stroma with dense acute and chronic inflammation. Spindle cells, large bizarre ganglion‐like cells and multivacuolated cells were seen. Variable reactivity in lesional cells were noted for vimentin, Alpha‐1‐antitrypsin (A1AT), factor XIIIa, CD68, CD95, CD117, Alpha‐1‐antichymotrypsin (A1ACT), CD34, AE1/3, S‐100 protein, EBER, CD63 and CD15. MIB‐1 showed 5–30% nuclear labeling. They were negative for cytokeratin AE1/3, smooth muscle actin, CD30, ALK‐1, EMA, desmin, CMV, HMB‐45 and Melan‐A. Follow up ranged from 2 weeks to 95 months (mean 54). One patient was lost to follow up; three underwent excision and one patient had below the knee amputation. Two patients developed metastases (one died of disease), and two patients are alive without evidence of disease. AMIFS are rare tumors that may involve joints and tendons leading to clinical diagnosis of ganglion cyst or tenosynovitis.

Malignant Melanoma Associated with Lichen Sclerosus in the Vulva of a 10‐Year‐Old

Abstract:  Malignant melanoma of the vulva in childhood is a rare neoplasm. Lichen sclerosus of the vulva in childhood is also a rare disease. The association of these two rare lesions in the vulva of young girls is extremely rare. We present a 10‐year‐old white girl with malignant melanoma associated with lichen sclerosus of the vulva. She had dark pigmentation of both the labia minora and posterior fourchette. The inner labia majora and fourchette showed whitish, glistening areas of skin. Histologic examination found mostly an in situ lentiginous/mucosal melanoma with focal invasion to a depth of 0.44 mm in the left upper labium majus. All specimens showed evidence of lichen sclerosus. Partial vulvectomy was performed, and no metastases were detected at the time of treatment. The patient has been disease free for the 12 months after treatment. It is critical for physicians to realize that melanoma can occur in children, and although rare, can occur in the vulva. We feel that lichen sclerosus in this instance may represent a pattern of host immune response to melanoma.

Subungual Myxoid Pleomorphic Fibroma

The authors report an example of pleomorphic fibroma in a unique site: the subungual space of the thumb. A 54-year-old man presented with paronychia and markedly thickened hyperkeratotic nail. The nail plate was removed, and an exophytic, red, friable, granulation tissue-like lesion was revealed subungually. The lesion was diagnosed clinically as pyogenic granuloma. Excisional biopsy was performed. Histologically, the lesion showed a hypocellular fibroma with myxoid areas and dilated blood vessels. Interspersed with ordinary appearing fibroblasts, there were bizarre, atypical fibroblasts with hyperchromatic and large, pleomorphic nuclei and multinucleated floret-like giant cells. These atypical cells showed strong immunoreactivity with antibodies against CD34 and vimentin. Occasional positivity was noted with factor XIIIa and alpha-1-antichymotrypsin, whereas no reactivity occurred with alpha-1-antitrypsin, actin, or S-100 protein. The entity of pleomorphic fibroma has been reported in many body sites; however, this is the first case to be reported in the subungual space.

Thomsen-Friedenreich (T) antigen: a possible tool for differentiating sebaceous carcinoma from its simulators.

The Thomsen–Friedenreich (T) antigen is a cryptic glycoprotein, referred to as tumor antigen or cancer-associated antigen because it is absent or masked by some carbohydrates in normal tissues, but present in many human cancers. The latter include gastrointestinal, lung, pancreatic, mammary, and some ovarian carcinomas. Cancer cells frequently undergo incomplete glycosylation resulting in the appearance of precursor structures that normally would be absent like the case with the T antigen. T antigen can be detected by several different reagents including monoclonal antibodies and several plant lectins–e.g., Arachis hypogea (peanut agglutinin). The aim of the current study was to evaluate the expression of T antigen in sebaceous carcinoma and to compare it with its simulators. The authors studied the immunohistochemical expression of T antigen in 45 skin biopsy and excisional specimens obtained from the archives of their dermatopathology laboratories, including 8 cases of sebaceous carcinoma, 15 cases of sebaceous adenoma, 9 cases of sebaceoma, 1 case of basal cell carcinoma with sebaceous differentiation, and 12 cases of basal cell carcinoma with cytologic atypia. Sebaceous carcinoma was unique in expressing a strong, diffuse cytoplasmic T antigen reactivity (7 of 8 cases) along the immature basaloid cells and the intermediate cells. However, sebaceous adenoma, sebaceoma, and basal cell carcinomas expressed negative reaction in the basaloid cells and mild reactivity in the intermediate cells. Mature sebocytes showed a strong reaction in all cases. The authors concluded that T antigen expression may be a helpful tool in differentiating sebaceous carcinoma from other sebaceous lesions that may simulate it histologically.

AlloDerm Grafting for Large Wounds after Mohs Micrographic Surgery

&NA; The authors have indicated no significant interest with commercial supporters.

Sebaceous carcinoma and the T-antigen.

Carcinomas of sebaceous glands are uncommon. They are traditionally classified into ocular and extraocular sebaceous carcinomas (SC). Ocular SC tend to be more common and more aggressive than extraocular SC. However, the latter can occasionally follow a fatal course. Histologically, SC should be classified into 1) SC in situ; 2) SC, infiltrating, low-grade with or without pagetoid spread; 3) SC, infiltrating, high-grade, with or without pagetoid spread; and 4) SC with extraocular and extracutaneous involvement, including metastases. Immunohistochemistry plays a minor role in the diagnosis of SC. Thomsen-Friedenreich (T) antigen can be a helpful tool in differentiating SC (strong T-antigen reactivity in basaloid cells) from other mimicking neoplasms (basaloid cells are T-antigen negative). The histologic differential diagnosis, pathogenesis, and management of SC are reviewed.

Floaters in Mohs micrographic surgery.

Background Floaters are dislodged pieces of tumor tissue than can obscure Mohs micrographic surgery (MMS) frozen sections and confound their interpretation. Objective To understand the common causes of floaters and identify management strategies. Methods An initial virtual consensus conference of Mohs surgeons based on a 60‐item questionnaire. Data were validated in interviews with randomly selected Mohs surgeons. Results Based on retrospective reporting of 230 surgeon‐years and 170,404 cases of MMS by 26 surgeons, the mean rate of floaters per tumor treated was 1.8%, and the rate of floaters per tissue block was 0.70%. Not wiping blades between cuts when a stage is separated into subunits can predispose to floaters. There was also strong consensus that basal cell carcinomas, ulcerated tumors, and tissue from the first stage were more likely to yield floaters. There is little consensus on how to manage floaters, with possibilities including taking additional sections, taking an additional stage, or simply noting the floater. Conclusion Floaters are not rare and can complicate MMS margin assessment. There is significant expert consensus regarding the causes of floaters and the tissue features that may predispose to them. Floaters may be prevented by minimizing their likely causes. There is less consensus on what to do with a floater.

CD34‐positive myxoid dermatofibrohistiocytoma of the skin: an indolent post‐traumatic tumor that can be mistaken for dermatofibrosarcoma protuberans*

To the Editor, The list of skin tumors and tumor-like lesions that are CD34 positive is long and can make the task of arriving at the correct diagnosis more difficult in superficial shave biopsies. It includes many fibrous and fibrohistiocytic lesions, namely dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSPs). We describe an indolent post-traumatic dermal tumor composed of CD34-positive spindle cells and factor XIIIa-positive dendritic cells in a 48-year-old woman who presented with bilateral calf nodules, clinically diagnosed as DFs. Microscopic examination of the biopsy specimens from the right calf showed a DF. A well-circumscribed fibrohistiocytic tumor with myxoid changes located in the midand deep reticular dermis was identified in the left biopsy (Fig. 1). This latter lesion was unencapsulated and composed of loosely dispersed, small spindle, dendritic and histiocytic cells with a myxoid stroma (Fig. 2) that contained wispy collagen. The lesion was not associated with adnexal structures and lacked cytologic atypia, mitoses or storiform/ palisaded arrangements. The tumor cells had bland oval nuclei and over 95% stained positive for CD34 (Fig. 3A). Scattered dendrocytes were factor XIIIa positive, while the spindle cells were factor XIIIa negative (Fig. 3B). Masson trichrome highlighted the meshwork of collagen bundles in the background. All cells were strongly vimentin positive, with infrequent labeling of nuclei by Ki-67 (1%). The stroma contained acid mucopolysaccharides that were stained positive for Alcian blue (pH 2.5) and negative for periodic acid-Schiff. The tumor cells were negative for S-100, epithelial membrane antigen, CD68, smooth muscle actine, alpha-1antichymotrypsin, CD99 and FVIII-related antigen. Based on the histologic features and immunohistochemical profile, our case is best classified as a CD34-positive myxoid dermatofibrohistiocytoma (DF/fibrous histiocytoma), a term coined in 1996 by Silverman and Brustein, who described an unusual subungual tumor with a similar immunohistochemical profile. The current tumor described herein and the one originally described in 1996 now appear to better belong to the entity described by Fetsch et al., classified as superficial acral fibromyxoma (SAFM), and share many similar morphologic features. SAFM tends to involve the hands and feet, particularly the nail bed, and is composed of CD34positive spindle/stellate cells arranged in fascicular or loose storiform growth patterns within a myxoid matrix and associated with abundant mast cells and prominent microvasculature. There is usually no atypia or increased mitotic rate. The current case did not show general morphologic features of DF such as epidermal hyperplasia, collagen trapping, sclerotic collagen or lymphohistiocytic tissue response. In addition, DF is not usually strongly CD34 positive and generally does not necessitate complete excision. Most DFSPs are CD34 positive and can be focally FXIIIa positive. However, the lesion in this case was well circum*Presented in part at the 4th Joint Meeting of the International Society of Dermatopathology, Washington, DC, February 2001. Dr Hassanein is currently the medical director of the Florida Dermatologic Surgery & Aesthetics Institute and Florida Pathology, The Villages, FL 32159, USA