Ramon L. Sanchez

Extramammary Paget Disease Is Characterized by the Consistent Lack of Estrogen and Progesterone Receptors But Frequently Expresses Androgen Receptor

Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease.

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.

ObjectiveThis study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas. Summary Background DataAmplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. MethodsThe differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. ResultsAmplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4− to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1− to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. ConclusionsAmplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Expression of CD95 (Fas) in Sun-Exposed Human Skin and Cutaneous Carcinomas

Carcinomas of the skin are by far the most common human malignancies. Continuous exposure to ultraviolet (UV) light facilitates the development of precancerous lesions (actinic keratosis [AK]) that may progress to invasive squamous carcinomas. Apoptosis, triggered by the activation of CD95 (Fas), is one of the most important defense mechanisms against UV light–induced carcinogenesis in experimental models, but the dynamics of CD95 expression in patients with sun‐induced lesions are largely unknown.

Clinical and histologic features of striated muscle hamartoma: Possible relationship to Delleman's syndrome

We describe 5 new cases of striated muscle hamartoma (SMH) and review the 7 cases previously described in the literature. Eleven of the 12 patients had single lesions centrally located on the chin (4), near the ala of the nose (3), on the upper chest (3), and on the upper lip (1). Histologically all of the lesions were characterized by a central core containing bundles and individual fibers of skeletal muscle as well as other mesenchymal elements. The muscle fibers penetrated the dermis among numerous folliculo‐sebaceous structures. Of the 12 cases of SMH, 3 had other associated congenital anomalies including a cleft lip in 1 patient and a thyroglossal duel sinus in another with single lesions, and preauricular sinuses, low‐set ears and bilateral sclerocorneas in the case of multiple SMH. The relationship of SMH with oculocerebrocutaneous syndrome is discussed, and we conclude that at least some of the skin appendages associated with that syndrome are SMH.

GRANULOMATOUS EPIDIDYMO-ORCHITIS: SONOGRAPHIC FEATURES AND CLINICAL OUTCOME IN BRUCELLOSIS, TUBERCULOSIS AND IDIOPATHIC GRANULOMATOUS EPIDIDYMO-ORCHITIS

PURPOSE We reviewed and analyzed sonographic findings in granulomatous epididymo-orchitis in an attempt to differentiate this rare inflammatory entity from other causes of enlarged scrotum, such as tumors. MATERIALS AND METHODS We retrospectively reviewed sonographic features of 9 patients a mean of 41 years old with specific and nonspecific granulomatous epididymo-orchitis, including brucellosis in 7, tuberculosis in 1 and idiopathic granulomatous epididymo-orchitis in 1. Histological confirmation was obtained in 3 cases, and in the remaining 6 positive clinical manifestations and laboratory tests for brucellosis were accepted as the main criteria for the diagnosis of brucellar epididymo-orchitis. RESULTS The most notable echographic finding was an enlarged and heterogeneous epididymis, predominantly in the body and tail. Testicular involvement consisted of a diffusely hypoechoic testis or focal intratesticular areas. Thickening of the scrotal wall and tunica albuginea, and moderate hydrocele were also noted occasionally. Followup scans revealed intratesticular abscesses in 3 patients. CONCLUSIONS These echographic findings may suggest the diagnosis of granulomatous epididymo-orchitis in the appropriate clinical setting, and help to avoid unnecessary orchiectomy for benign disease.

Loss of mismatch repair proteins in sebaceous gland tumors

Background: Sebaceous gland neoplasms are rare tumors that are associated with visceral malignancies in patients with Muir–Torre syndrome (MTS). The majority of the MTS‐associated tumors reveal mutations in DNA mismatch repair (MMR) genes (most often hMSH‐2 and hMLH‐1) and microsatellite instability. The sebaceous gland lesions in patients with MTS can often precede or occur concurrently with the visceral neoplasms. The early recognition of those lesions and their differentiation from sporadic sebaceous gland tumors are critical for proper patient management. Here we investigate the MMR gene expression in a variety of sebaceous gland tumors, with or without associated visceral malignancy.

Thrombotic vasculopathy associated with cryofibrinogenemia

Cryofibrinogenemia refers to the presence of cold-precipitable plasma proteins associated with a variety of disorders, including malignancies, inflammatory processes, and thrombohemorrhagic phenomena. Few cases of essential or primary cryofibrinogenemia are reported. We report a case in a 48-year-old man of essential cryofibrinogenemia and hemorrhagic necrosis of the ears and of the upper and lower extremities. Histopathologic studies demonstrated extensive eosinophilic thrombi in the dermal vasculature, with minimal inflammation and no vasculitis. Cryofibrinogenemia should be considered in the investigation of patients with otherwise unexplained cold intolerance and dermal thrombosis associated with minimal or no inflammation.

Development of Human Papillomavirus Type 16 Associated Squamous Cell Carcinoma of the Scrotum in a Patient with Darier's Disease Treated with Systemic Isotretinoin

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Dariers disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies.

Solar elastotic bands of the forearm: An unusual clinical presentation of actinic elastosis

Actinic damage of dermal tissues produces several distinct clinical patterns. Three patients are described as having discrete, soft, cordlike bands on the forearms that extend from dorsal areas of actinic damage and senile purpura to greatest prominence in flexural regions with less solar damage. Histochemical analyses and light and electron microscopy studies of the plaques showed changes consistent with solar elastosis. The clinical variants of actinic elastosis and the possible origins of the abnormal elastic fibrils found in the dermis of chronically sun-damaged skin are discussed. Solar elastotic bands are an unusual form of actinic degeneration.

Nephrogenic systemic fibrosis is associated with transforming growth factor β and Smad without evidence of renin-angiotensin system involvement

BACKGROUND The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-beta), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-beta expression and fibrosis in other organ systems. OBJECTIVE We sought to investigate whether these mechanisms were involved with NSF. METHOD Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-beta, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1). RESULTS TGF-beta was detected in 8 of 11 samples of NSF. Smad 2/3 nuclear staining was seen in 8 of 11 samples. Conversely, only faint staining for ACE was seen in 2 of the 11 specimens. No AT1 staining was seen. LIMITATIONS We did not perform our studies on a cohort of comparable patients with renal dysfunction without NSF. Our technique may not have been sufficiently sensitive to detect renin-angiotensin system involvement. CONCLUSIONS TGF-beta, as well as its second messengers, Smad 2/3, appears to be associated with the fibrosis seen in NSF. No definitive evidence of renin-angiotensin system involvement could be determined.