Histopathologic pitfalls of Mohs micrographic surgery and a review of tumor histology.

Mohs micrographic surgery is a specialized subset of staged surgical excisions with each subsequent stage being driven largely by the histologic findings of the previous stage. Therefore, it is imperative that histologic analysis is performed in an accurate manner. Frozen section and tissue flattening is a crucial step in Mohs surgery. Frozen sections introduce certain artifacts and these artifacts must be interpreted in the correct context. Basal and squamous cell carcinomas are the most common tumors encountered in Mohs micrographic surgery, and their histopathology is also associated with certain "pitfalls". Basal cell carcinoma should be distinguished from hair follicles, folliculocentric basaloid proliferations, poromas, nevus sebaceous, desmoplastic trichoepitheliomas, and spiradenomas, to name but a few histologic entities. Similarly, squamous cell carcinoma should be distinguished from hypertrophic actinic keratoses, pseudoepitheliomatous hyperplasia, sebaceous carcinoma, and microcystic adnexal carcinoma. In addition, there are numerous subtypes of basal cell and squamous carcinomas that the Mohs surgeon should be aware of due to differences in the biologic behavior of these tumors. This review presents a number of the common histologic pitfalls of Mohs micrographic surgery and a review of tumor histology.

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.

Intraoral cellular blue nevus: report of a unique histopathologic entity and review of the literature.

The blue nevus is found most frequently on the skin; however, in rare instances, it has been reported on oral mucous membranes. Intramucosal nevi make up more than one half of all reported intraoral melanocytic nevi. The common blue nevus is the second most common variant. Among the 3 variants of blue nevi, the cellular variant occurs less frequently than the common and combined variants. We present a rare case of intraoral cellular blue nevus that occurred on the oral mucosa of the hard palate. Because of the clinical and microscopic resemblance of the cellular blue nevus to melanoma and the rarity of this lesion in the oral cavity, recognition and accurate diagnosis are critical.

Cutaneous mastocytosis in a patient with primary Sjögren's syndrome.

Mast cells have been linked to rheumatoid arthritis (RA) and are essential to the pathogenesis of RA-like disease in a mouse model. We describe a 34-year-old woman who developed Sjögren's syndrome concurrently with telangiectasia macularis eruptiva perstans (TMEP), a rare form of cutaneous mastocytosis. The patient had sicca symptoms with an abnormal minor salivary gland biopsy and decreased salivary flow, peripheral neuropathy, an 80 pound weight loss, and a macular erythematous rash that exhibited superficial perivascular mast cell infiltrates on biopsy of lesional skin. This case further underscores the link between mast cells and the development of autoimmunity.

Peritumoral fibrosis in basal cell and squamous cell carcinoma mimicking perineural invasion: potential pitfall in Mohs micrographic surgery.

BACKGROUND: Perineural invasion (PI) in cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is linked to an aggressive course. We describe a histologic mimic for PI that we termed peritumoral fibrosis (PF). OBJECTIVE: To describe the morphologic changes associated with PF and to determine the incidence of PF and PI in Mohs frozen sections of BCC and SCC. MATERIAL AND METHODS: All cases of BCC and SCC that were treated by Mohs micrographic surgery (MMS) at the Skin and Cancer Center, University of Florida College of Medicine, Gainesville, Florida, and the Center for Dermatology and Skin Surgery, Tampa, Florida, during the period from January 1, 2003, to August 1, 2004, were reviewed for the presence of PI and PF. The latter was defined as the presence of concentric layers of fibrous tissue that either surround and/or were surrounded by tumor formations mimicking perineural or intraneural invasion. Seven hundred six cases of BCC and 264 cases of SCC were surveyed. Eleven cases (10 BCC and 1 SCC) with equivocal areas were destained, and immunohistochemical staining with S-100 protein was performed, proving actual PI in all of these cases. Available original hematoxylin-eosin biopsy slides were correlated with the MMS frozen sections. RESULTS: PF was noticed in 4.5% of SCCs and 5.8% of BCCs. The incidence of unequivocal PI was noted to be 2.6% in SCC and 2.1% in BCC. CONCLUSION: We describe a specific pattern of fibrosis noted in BCC and SCC that we called PF. It shows concentric layers of fibrous tissue surrounding and/or surrounded by tumor formations and resembles carcinomatous perineural and/or intraneural invasion. Moreover, PF was found to be a sensitive marker for PI. Mohs micrographic surgeons should be aware of this phenomenon to avoid triggering unnecessary steps in managing these cases, such as irradiation.

Malignant melanoma associated with lichen sclerosus in the vulva of a 10-year-old.

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.

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.

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.

Lichen planus actinicus.

Lichen planus actinicus is a photodistributed variant of lichen planus that most often occurs in individuals with dark complexions. Sunlight seems to be a triggering factor in most cases. Several clinical morphologic patterns have been described, and multiple therapies with variable results have been used. The lesions in some patients may remit spontaneously with sun avoidance.

beta-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.