Christopher S Hale

Vulvar nevi, melanosis, and melanoma: An epidemiologic, clinical, and histopathologic review

Pigmented vulvar lesions are present in approximately 1 in 10 women and include melanocytic and nonmelanocytic proliferations. Vulvar nevi, melanosis, and melanoma are particularly challenging because of the similarity of their clinical and/or histopathological presentation. As a result, they are often difficult to diagnose, may result in patient and physician anxiety, and can lead to unneeded, potentially disfiguring surgical procedures. Because it is often detected late, vulvar melanoma carries a poor prognosis with associated significant morbidity and mortality, underscoring the importance of prompt recognition and treatment. In this review, we analyze the distinct epidemiologic, clinical, and histopathologic characteristics of vulvar nevi, melanosis, and melanoma, discuss treatment options, and propose a practical, systematic approach to facilitate formulation of a differential diagnosis and initiation of appropriate management.

Mitotic rate in melanoma: prognostic value of immunostaining and computer-assisted image analysis

The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm2 can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm2) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate.

Triple Synchronous Primary Gynecologic Carcinomas A Case Report and Review of the Literature

Double synchronous primaries are known to occasionally occur in gynecologic cancers. Cases of triple or quadruple synchronous primaries, with only 4 case reports in the literature, are extremely rare. The authors report the case of a 49-year-old para 2-0-0-2 woman who presented for surgical management of metastatic ovarian adenocarcinoma diagnosed at an outside institution. On examination of the surgical specimen, 3 synchronous primary carcinomas with multiple histologic features were identified within the ovaries, uterus, and cervix. Although rare, the possibility of triple synchronous primary malignancies should be considered when evaluating gynecologic malignancies.

Papular acantholytic dyskeratosis of the vulva associated with familial Hailey-Hailey disease.

Papular acantholytic dyskeratosis (PAD) of the vulva is a rare, chronic disorder first described in 1984. It presents in young women as white to skin‐coloured smooth papules over the vulva, which are persistent but asymptomatic. Histologically, there is hyperkeratosis and focal parakeratosis with acantholytic and dyskeratotic cells forming corps ronds and grains, placing PAD within Ackermans spectrum of focal acantholytic dyskeratoses with Hailey–Hailey disease (HHD) and Darier disease. There have been 17 previous reports of PAD of the vulva, to our knowledge. Only one demonstrated a familial pattern, and none of the cases was associated with a family history of HHD. This is the first report of PAD and HHD in a single family, suggesting that PAD and HHD lie on a spectrum of disease and are genetically linked.

Polyurethane foam: an underrecognized cause of foreign body granulomas.

To the Editor, We recently received a shave biopsy, from the forearm of a 71-year-old patient, status post-multiple hospitalizations for orthopedic procedures. Two to three months after her most recent discharge, the patient noticed the development of an erythematous, slightly indurated black spot on her forearm. Histopathologic examination showed a dermal foreign body granulomatous reaction surrounding particles of refractile, non-polarizable foreign material (Fig. 1). The particles were angulated, nonpigmented and appeared porous. After excluding common dermal fillers and other foreign bodies, a careful search of the literature enabled us to identify the foreign material as degrading polyurethane foam. Polyurethane foam is widely used in medicine. First patented in the 1960s,1 polyurethane has long been popular as a dressing for burns, ulcers and surgical wounds. Its porous trabecular structure absorbs wound exudate, acts as a scaffold for fibroblasts and supports re-epithelialization.2 As the foam degrades, it may stimulate a granulomatous response, in which foreign body macrophages engulf broken struts of foam.3 In the 1980s, silicone breast implants were coated with polyurethane foam to reduce the incidence of capsular contracture.4 These coatings fragment over time,5 and particles of foam may migrate beyond the implant capsule to surrounding soft tissue and regional lymph nodes.6– 9 The foam fragments are readily identifiable by their characteristic angular morphology, and their nature may be confirmed by spectroscopy.8 Polyurethane foam may also comprise a minor component of some silicone granulomas induced by breast implant leakage.8 Concern that degradation of polyurethane foam could lead to release of toxic toluene diamine (TDA) led to Fig. 1. H&E stain 200X (above) and 400X (below). Angulated spicules of degenerating polyurethane foam, engulfed by foreign body macrophages.

Bilateral tubulocystic renal cell carcinomas in diabetic end-stage renal disease: first case report with cytogenetic and ultrastructural studies

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.