J. Fernando Val-Bernal

Churg–Strauss syndrome and sudden cardiac death

Churg-Strauss syndrome is a rare disorder characterized by necrotizing vasculitis, granulomas with eosinophilic necrosis, and tissue infiltration by eosinophils. Sudden cardiac death is rarely described in Churg-Strauss syndrome. In this article, we describe a case of Churg-Strauss syndrome with multiorgan involvement manifested as sudden cardiac death. To the best of our knowledge, this form of presentation has not been reported. A 49-year-old woman was found dead in her room. No premonitory complaints had been noted during the days preceding her death. Past medical history did not reveal any relevant illness. At autopsy, multiorganic Churg-Strauss syndrome with prominent cardiac involvement was found. Therefore, this syndrome in the active vasculitic phase may be asymptomatic and may involve predominantly the heart. This variant of the syndrome may be fulminant and present as sudden cardiac death. This form can only be elucidated by autopsy study.

Extravulvar subcutaneous cellular angiofibroma

Cellular angiofibroma is a rare distinctive mesenchymal neoplasm of the vulva or perineal region. We report here one unique extravulvar case. A 43‐year‐old woman presented with an asymptomatic tumor, 7 cm in diameter, located in the subcutaneous tissue of the chest below the left submammary sulcus. Histologically, the lesion was composed of uniform spindled stroma cells, numerous thick‐walled vessels, and scarce mature adipocytes. An additional feature was the presence of prominent perivascular lymphoid aggregates. The stromal cells were positive for vimentin and negative for CD34 and muscle, epithelial, myoepithelial, or neural markers. Although nasopharyngeal angiofibroma or the group of acral angiofibromas have a concurrent heading, cellular angiofibroma should not be mistaken with them. Differential diagnosis of this distinctive tumor especially includes aggressive angiomyxoma, angiomyofibroblastoma, superficial angiomyxoma, vascular myxolipoma, and other tumors with spindle cells reminiscent of those in angiofibroma.

Testicular metastases from solid tumors: an autopsy study.

In a retrospective study of 738 consecutive autopsies of adult males with solid malignant neoplasms, five (0.68%) were shown to have metastatic deposits within the testis. These were metastases from bronchial carcinoma (three cases), melanoma (one case), and pancreatic endocrine carcinoma (one case). The mean age of the patients with solid tumors metastatic to the testis was 60 years (range, 32 to 83 years). The metastases from the solid tumors presented two patterns: destructive and/or focal interstitial. The destructive pattern was characterized by sheets of malignant cells that destroyed and replaced the seminiferous tubules. The interstitial pattern was characterized by tumor cells within the interstitium without involvement of the seminiferous tubules. All metastases showing the destructive pattern were macroscopically evident. Approximately 40% of the metastatic deposits were microscopic and showed a focal interstitial pattern. These cases are not easily identified unless a sufficient number of tissue blocks are sampled and carefully scrutinized. In 20% of the cases the metastatic deposits were bilateral. Improved diagnostic skills and treatment protocols in the last 11 years apparently have not significantly affected incidence, distribution, or the pattern of metastatic spread of solid tumors to the testis.

Benign mucinous metaplasia of the penis. A lesion resembling extramammary Paget's disease

Benign mucinous metaplasia in the surface epithelium of the genital area is rare and has only been reported once in the vulva. A unique case of benign mucinous metaplasia of the prepuce in a 65‐year‐old man is reported here. The lesion measured 0.6 cm, was located in the mucous surface of the foreskin, and showed acid mucin containing cells. We regard benign mucinous metaplasia as a reactive rather than a neoplastic process. The main lesions to be considered in the differential diagnosis are mucinous syringometaplasia, extramammary Pagets disease, cutaneous squamous cell carcinoma in situ with mucinous metaplasia, superficial spreading malignant melanoma, and epidermotropic metastasis. The confinement of mucin‐containing cells to the epidermis, the absence of nuclear atypia, the basal orientation of the nuclei, the predominant location of the cells in the upper layers of the epithelium, and the fact that the mucinous cells are replacing the squamous epithelium rather that infiltrating it, all assist in recognizing mucinous metaplasia of the penis as a specific and benign entity.

Cutaneous lipomatous neurofibroma: characterization and frequency

Background:  There are numerous variants of cutaneous neurofibroma reflecting its manner of growth and histologic composition. Lipomatous neurofibroma is the latest described variant with only eight cases reported.

Plexin B1 is downregulated in renal cell carcinomas and modulates cell growth.

Plexins are a family of transmembrane receptors that interact with the repulsive axon guidance molecules (Semaphorins) in neural tissues. In extraneural tissues, plexins are involved in other cellular functions often altered in neoplastic cells, such as adhesion, migration, and apoptosis. Plexin B1 has been implicated in the regulation of Akt, which is an activated pathway in renal cell neoplasms, and only 1 report has emphasized its role as an oncogenic factor. Furthermore, plexin B1 is located in 3p21, which is a chromosomal region deleted frequently in renal cell carcinomas. In accordance with a hypothetical oncogenic role for plexin B1, we have shown by reverse transcription-polymerase chain reaction that plexin B1 is expressed in nonneoplastic renal tissue, and it is severely downregulated in clear cell renal carcinomas. We have also demonstrated by immunohistochemistry on tissue microarrays that plexin B1 protein is absent in more than 80% of renal cell carcinomas (169 in 209 carcinomas examined). Otherwise, all kinds of renal tubules showed strong membrane reactivity. Moreover, when we have induced plexin B1 expression with an expression vector in the renal adenocarcinoma cell line ACHN, a marked reduction in proliferation rate was produced. Altogether, this evidence suggests a possible role for plexin B1 in renal oncogenesis.

Incidental localized (solitary) epithelial mesothelioma of the pericardium Case report and literature review

Primary mesotheliomas of the pericardium are rare tumors. They may occur in diffuse, multiple, and localized forms. Most of the pericardial mesotheliomas are multiple or diffuse growths encasing the heart, localized forms being distinctly uncommon. We report a localized mesothelioma of the pericardium found incidentally at the autopsy of a 76-year-old woman. The neoplasm measured 3.6 x 2.4 x 2.5 cm., was well circumscribed, and affected the entire thickness of the myocardium extending from the epicardium to the endocardium of the anterior wall of the right ventricle. The tumor was epithelial in type, showed an immunohistochemical profile compatible with mesothelioma, and was DNA aneuploid. A review of the literature yielded four cases of localized pericardial mesothelioma, including the present. Most cases are seen in women and are of the epithelial variant. There is a wide age range at presentation. Localized mesotheliomas are capable of aggressive behavior. Nevertheless, in contrast to diffuse tumors, complete surgical excision may be curative. Differential diagnosis includes solitary fibrous tumor, synovial sarcoma, epithelioid angiosarcoma, and adenomatoid tumor of the pericardium.

Pagetoid dyskeratosis of the prepuce. An incidental histologic finding resembling extramammary Paget's disease.

Background: Pale cells resembling those of pagets disease have been seen as an incidental finding within the epidermis in a variety of benign papules most commonly located in intertriginous areas. This lesion, called pagetoid dyskeratosis, is considered a reactive process in which a small part of the normal population of keratinocytes is induced to proliferate. Among the inductors friction is suspected. As far as we know, these cells have not been reported in the penis.

Dermatofibroma with granular cells.

A new histologic variant of dermatofibroma, only briefly alluded to in dermatological literature is reported. This tumor was located in the back of a 24‐year‐old man. It was present for about 2 years and had a history of trauma 2 months before excision. The lesion showed similar characteristics to those of conventional dermatofibroma as well as the presence of groups of granular cells identical to those seen in granular cell tumors. It is important to recognize dermatofibroma with granular cells because it may be confused with a variety of benign or malignant soft tissue tumors containing similar granular cells that entail different significance or prognosis. The immunohistochemical study supports a granular cell change in a dermatofibroma instead of a granular cell tumor that has been traumatized, with secondary formation of a dermatofibroma reaction.

Reorganization of Cajal bodies and nucleolar targeting of coilin in motor neurons of type I spinal muscular atrophy

Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by loss or mutations of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to degeneration and death of motor neurons. In this study, we have analyzed the nuclear reorganization of Cajal bodies, PML bodies and nucleoli in type I SMA motor neurons with homozygous deletion of exons 7 and 8 of the SMN1 gene. Western blot analysis revealed a marked reduction of SMN levels compared to the control sample. Using a neuronal dissociation procedure to perform a careful immunocytochemical and quantitative analysis of nuclear bodies, we demonstrated a severe decrease in the mean number of Cajal bodies per neuron and in the proportion of motor neurons containing these structures in type I SMA. Moreover, most Cajal bodies fail to recruit SMN and spliceosomal snRNPs, but contain the proteasome activator PA28γ, a molecular marker associated with the cellular stress response. Neuronal stress in SMA motor neurons also increases PML body number. The existence of chromatolysis and eccentric nuclei in SMA motor neurons correlates with Cajal body disruption and nucleolar relocalization of coilin, a Cajal body marker. Our results indicate that the Cajal body is a pathophysiological target in type I SMA motor neurons. They also suggest the Cajal body-dependent dysfunction of snRNP biogenesis and, therefore, pre-mRNA splicing in these neurons seems to be an essential component for SMA pathogenesis.