Stephen C. Somach

Fibronectin and the extracellular matrix in the perforating disorders of the skin.

Despite detailed microscopic descriptions and clinical observation, little is known regarding the pathogenesis of the perforating disorders of skin, which have traditionally been subdivided into numerous microscopic entities associated with various clinical settings. An increasing body of evidence now suggests that the perforating disorders of skin are akin, and may constitute an expanded single pathologic entity. Each of the classic perforating disorders of skin, including elastosis perforans serpiginosa, perforating folliculitis, reactive perforating collagenosis, Kyrles disease, and perforating disorder of uremia, have been shown to extrude collagen, elastin, and related extracellular matrix components through the epidermis. Considering a shared pathogenic mechanism among these entities, we explored the possible role of the extracellular matrix, in particular fibronectin, in perforating disorders of skin. Using immunohistochemical and serum determinations of extracellular matrix constituents, including fibronectin, collagen type IV, laminin, and tenascin, we showed consistent serum elevation and/or deposition of fibronectin, in each case, without a commensurate increase in laminin, collagen type IV, and tenascin. We propose that elevated serum and tissue concentrations of fibronectin may be responsible for inciting, in a physiologically aberrant manner, increased epithelial migration and proliferation culminating in perforation.

Histomorphologic and immunophenotypic analysis of fibrofolliculomas and trichodiscomas in Birt-Hogg-Dube syndrome and sporadic disease.

Background:  Fibrofolliculomas and trichodiscomas are benign dermal neoplasms that likely derive from the mantle of the hair follicle and can occur sporadically or in association with Birt–Hogg–Dube syndrome (BHDS). Little is known about the pathogenesis and immunophenotypic properties of these entities.

Cutaneous collagenous vasculopathy: a rare cutaneous microangiopathy.

Cutaneous collagenous vasculopathy is a rare microangiopathy of superficial dermal blood vessels. Patients present with telangiectatic macules, predominantly on the extremities. A skin biopsy specimen is necessary to distinguish cutaneous collagenous vasculopathy from generalized essential telangiectasia. Microscopically, cutaneous collagenous vasculopathy resembles the superficial telangiectasias of generalized essential telangiectasia but additionally shows hyaline material in thickened vessel walls. The amorphous pink material is periodic acid‐Schiff‐positive and resistant to diastase. We describe a series of four patients with cutaneous collagenous vasculopathy and highlight its clinical and histopathologic features.

Merkel cell polyomavirus: an update.

The list of neoplasias induced by viruses continues to grow with the recent discovery of polyomavirus DNA in Merkel cell carcinoma (MCC). Viruses are able to induce a variety of hematopoietic malignancies as well as several solid tumors. Solid tumors known to be induced by viruses include squamous cell carcinoma (human papillomavirus), Kaposi’s sarcoma (human herpesvirus 8) and leiomyosarcoma (Epstein-Barr virus), all of which share a high incidence in immunosuppressed patients. Epidemiological data showing a markedly increased incidence of MCC in patients with HIV infection and other forms of immunosuppression suggested a possible role for an infectious agent as an inducer of transformation. Feng et al.1 at the University of Pittsburgh recently identified DNA from a previously unknown polyomavirus in MCC. MCC samples were studied by digital transcriptome subtraction, a novel method of searching for viral transcripts. Briefly, two libraries of mRNA were prepared, the first from a single MCC and the second library from three pooled MCCs. Using reverse transcriptasepolymerase chain reaction (RT-PCR), copy DNA transcripts were generated from extracted tumor mRNA. After a number of complex steps involving trimmed sequences and sequence tags, comparative sequence analysis allowed cDNA transcripts of human origin to be subtracted, leaving the remaining sequences as candidate viral transcript sequences. Of the remaining 2395 candidate sequences, one transcript with homology to the African green monkey lymphotropic polyomavirus (LPV) and to human BK virus T antigen sequences was detected. Further amplification and investigation revealed a fusion transcript of the virus T antigen and human receptor tyrosine phosphatase, indicative of viral DNA integration into the tumor genome. Using PCR primer sets, Merkel cell polyomavirus (MCV) sequences were detected in 8 of 10 MCCs, but in only 5 of 59 (8%) control samples from other body sites and 4 of 25 (16%) from control skin specimens. MCV DNA was also found to be clonally integrated into tumor genome in 6 of 8 MCCs, suggesting that infection and genome integration occurs in the tumor before tumorigenesis. The MCV is closely related to an LPV found in African green monkeys, unlike the four other known human polyomaviruses, which belong to the simian virus 40 (SV40) subgroup. Polyomaviruses are non-enveloped small circular double-stranded DNA viruses. Their genome encodes three structural proteins: VP1, VP2 and VP3, and two early tumor antigens: small T (ST) and large T (LT). Human polyomaviruses include JC and BK viruses, described in the early 1970s, both usually acquired in childhood.2– 4 The mode of transmission is not known. BKV causes nephropathy in kidney transplant patients, and JCV causes progressive multifocal leukoencephalopathy in patients with HIV infection and in other immunocompromised individuals. The other human polyomaviruses are KIV and WUV, which were discovered in 2007 in nasal secretions of children.5,6 They are not known to have any disease associations in humans. The identification of viral DNA within a tumor does not per se implicate that virus as oncogenic. In viral infection of a natural host, the entire viral genome is replicated, resulting in production of more viral particles, with eventual host cell lysis and death. In contrast, in viral-induced oncogenesis, portions of the viral genome are incorporated into permissive host DNA and persist, eventually leading to transformation. As would be expected in an oncogenic virus, only portions of the MCV genome have been consistently identified in MCC. In a study by Sastre-Garau et al.7 analyzing 10 cases of MCC, MCV DNA sequences were identified in all cases, but not in any of 1241 specimens of a variety of other tumors. The viral sequences common to all cases were the replication origin, the ST and the 5’ part of the LT antigen. DNA encoding for structural proteins was found in only one tumor. A single integration site was found for viral DNA in each of the tumors, within both primary tumors and their metastatic deposits, indicating that the integration event took place prior to clonal expansion of the tumor. Integration sites varied from tumor to tumor. The status of cellular genes potentially involved in oncogenesis located near the integration site was evaluated. Several

Ocular adnexal oncocytoma : A case series and clinicopathologic review of the literature

The authors report the clinical, microscopic, and ultrastructural features of four oncocytic lesions involving the ocular adnexa. Three of the lesions originated in the ocular caruncle of elderly women, and a single case was encountered from the medial eyelid of an elderly man. Each lesion clinically presented as a slow-growing, painless, red mass. The histopathologic features were distinctive, with polyhedral cells containing granular eosinophilic cytoplasm found to consist of large numbers of mitochondria on ultrastructural examination. Of the 40 cases previously reported primarily in the ophthalmologic literature, the cases reported here similarly involved the eyelid and associated ocular adnexa with a predilection for elderly women. Oncocytomas probably represent an age-associated metaplastic and neoplastic transformation of the glandular epithelium comprising the ducts of salivary glands.

The inadequacy of punch-excised melanocytic lesions: sampling through the block for the determination of "margins".

BACKGROUND Dermatopathologists often are asked by clinicians to report margins on punch excisions of melanocytic lesions. OBJECTIVE We sought to determine the adequacy of surgical margins on melanocytic lesions submitted with intention of complete excision using punch removal technique. METHODS We conducted prospective analysis of surgical margins on 266 consecutive patients who underwent attempted complete removal of 405 melanocytic nevi submitted as punch and fusiform excisions. RESULTS Of 206 nonbisected punch excisions, 127 (62%) had final positive margins. Of 159 bisected punch excisions, 76 (48%) had final positive margins. Of 40 elliptical excisions, two (5%) had final positive margins. LIMITATIONS Information on the perilesional rim of nonpigmented skin included in the excision was not available. CONCLUSIONS Of punch excisions, 56% had positive margins. Importantly, 30% of these punch excised specimens were negative on initial levels but had positive margins after extensive sectioning, affirming that fusiform excisions are the preferred method to evaluate margins in melanocytic lesions.

Multiple follicular cysts, infundibular type with vellus hairs and solar elastosis of the ears: a new dermatoheliosis?

Background:  Vellus hair cyst is an uncommon developmental abnormality of the vellus follicle histologically defined as a stratified squamous epithelial‐lined cyst containing one or more vellus hairs.

Herpes zoster granulomatous dermatitis: histopathologic findings in a case series

Several types of cutaneous reactions have been reported to arise at the site of herpes zoster (HZ) infection weeks to years after the acute disease. Among these, granulomatous reactions are the most frequently reported. In this study, we describe the spectrum of histopathologic findings of HZ granulomatous reactions observed in 26 patients with cutaneous lesions confined to the area of previous HZ eruption and compare them with biopsy specimens taken from 25 patients with acute HZ. All patients with persistent reactions from whom history was available presented within 12 weeks of the onset of the acute eruption. The most frequent findings were interstitial granulomatous dermatitis with lymphocytes, histiocytes and multinucleated giant cells displaying elastophagocytosis and a perineural, perivascular and perieccrine mononuclear inflammatory infiltrate rich in lymphocytes and plasma cells. Less common features included intra‐arrector and peri‐arrector pili granulomas, follicular dilatation and hyperkeratosis, and vasculitis. Specimens from patients with acute HZ were found to have small numbers of perineural plasma cells and most had subtle granulomatous inflammation, in patterns similar to the group with late granulomatous reactions. Our findings suggest that granulomatous reactions to varicella zoster virus represent a persistent evolving inflammatory reaction after acute infection.

Benign keratosis with a spectrum of follicular differentiation: a case series and investigation of a potential role of human papilloma virus

Background: A variety of dermatopathologic entities are histologically defined by the presence of follicular differentiation. Follicular differentiation confined to the epidermis may follow induction from dermal mesenchymal proliferations, as in a nevus sebaceus of Jadassohn, or represent endogenous proliferations such as the tumor of the follicular infundibulum or trichilemmoma.

Cutaneous epithelioid angiomatous nodule: a case with metachronous lesions.

Cutaneous epithelioid angiomatous nodule is regarded as a benign vascular proliferation on the spectrum of epithelioid vascular lesions, probably most closely related to epithelioid hemangioma. Most patients present with solitary lesions. We present an unusual case of an 84-year-old man with multiple epithelioid angiomatous nodules that developed over a 1-year period. Given the multiple lesions, an extensive evaluation for a possible infectious etiology was undertaken. However, no evidence of an infectious agent was identified. The histopathologic differential diagnosis for epithelioid vascular lesions is reviewed.