Philip H. Cooper

Lobular capillary hemangioma: The underlying lesion of pyogenic granuloma

Pyogenic granuloma (PG) has a diagnostic, lobular arrangement of capillaries at its base. The lobules consist of discrete clusters of endothelial cells, and the lumina vary from indistinct to prominent. The superficial portions of the lesion may undergo secondary, nonspecific changes including stromal edema, capillary dilation, inflammation, and a granulation tissue reaction. PG has often been equated with these inflammatory changes but objective diagnostic criteria have not been presented. To avoid confusion and focus on the intrinsic nature of PG we suggest the accurate, descriptive term, lobular capillary hemangioma (LCH). A review of 639 vascular lesions of the oral cavity and upper respiratory tract yielded 73 cases with the characteristic features of LCH. The lip was the most common site (38%), followed by the nose (29%), oral mucosa (18%), and tongue (15%). LCH usually presents as a spontaneous, painless, bleeding mass. There is a predilection for males less than 18 years old, females in the reproductive years, and an equal sex distribution beyond 40 years of age. No examples of LCH were found in 68 vascular lesions from the larynx or trachea.

Reassessment of malignant "angioendotheliomatosis". Evidence in favor of its reclassification as "intravascular lymphomatosis".

Malignant angioendotheliomatosis (MAE) is a lethal intravascular proliferation which has been thought to be of endothelial origin. In order to characterize its cellular nature, we studied 15 cases of MAE immunocytochemically, using antisera for factor VIII-related antigen, cytokeratin, epithelial membrane antigen, vimentin, blood group isoantigens, thoracic duct lining cell antigens (TDLCA), common leukocyte antigen, and Ulex europaeus I lectin. In 14 of 15 cases, common leukocyte antigen was observed in malignant intravascular cells. Similar reactivity for factor VIII-related antigen was present in 14 cases, but was largely restricted to cells enmeshed in fibrin-platelet thrombi, and probably represents adsorption of platelet-derived factor VIII by tumor cells. All cases failed to bind Ulex europaeus lectin and lacked immunoreactivity for TDLCA, cytokeratin, epithelial membrane antigen, and blood group isoantigens; two manifested positivity for vimentin. Immunofluorescent microscopy of frozen tissue in one case showed monoclonal IgM-kappa immunoglobulin on the surfaces of tumor cells. Electron-microscopic study of three cases disclosed a predominant cell type lacking features of epithelial or endothelial differentiation; a minor cell population displayed endothelial characteristics and was thought to be reactive. Four patients with typical MAE also had extravascular large-cell lymphoma in lymph nodes, spleen, adrenal glands, stomach, or soft tissues. Six patients showed clinical evidence of autoimmune disease. These results suggest that MAE displays lymphoid rather than endothelial differentiation.

Prognostic factors in squamous cell carcinoma of the lower lip

One hundred eighty-seven squamous cell carcinomas of the lower lip were examined microscopically to identify parameters that might predict metastasis and patient outcome. Excision specimens of 157 nonmetastasizing carcinomas (group I) were compared with specimens from 30 tumors that had metastasized (group II). The following features were recorded: architectural pattern; microscopic thickness (mm); cytologic grade; presence of muscle, nerve, or vessel invasion; inflammatory response; and mitotic rate. The mean thickness was 2.5 mm for group I tumors and 7.5 mm for group II tumors. Seventy-six per cent of the group I tumors were 3 mm thick or less, whereas only one group II lesion (3 per cent) was less than 3 mm thick. Five per cent of the group I neoplasms, compared with 77 per cent of the group II tumors, were at least 6 mm thick. Perineural invasion was seen in 5 per cent of the group I and 41 per cent of the group II lesions. Three per cent of the group I carcinomas had a dispersed pattern, compared with 57 per cent of those in group II. One group I lesion (0.6 per cent) and 37 per cent of the group II tumors were grade 4. Each of these differences was statistically significant (P less than 0.0001). For all lesions studied, metastases had occurred in 60 per cent with perineural invasion, 74 per cent measuring 6 mm or more, 77 per cent with a dispersed pattern, and 92 per cent that were grade 4. These important prognostic variables were best evaluated in the deeper portions of the lesions.

Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization.

Lymphoepithelioma of the nasopharynx has a strong association with Epstein-Barr virus (EBV). To test the hypothesis that lymphoepithelioma-like carcinomas occurring at other sites are also associated with EBV virus, we used in situ hybridization to analyze 20 cases of lymphoepithelioma and histologically similar lesions and five basaloid squamous cell carcinomas for evidence of EBV genomes. EBV genomes were demonstrated in six of six lymphoepitheliomas of the nasopharynx but in none of five basaloid squamous cell carcinomas. Only one of 14 lymphoepithelioma-like carcinomas was found to contain EBV genomes. The single positive lymphoepithelioma-like carcinoma occurred in the lung of an Asian patient, suggesting that ethnic or geographic influences may be important in determining whether EBV is associated with these nonnasopharyngeal neoplasms. Despite their histologic similarity, most lymphoepithelioma-like carcinomas probably have a different pathogenesis from nasopharyngeal lymphoepithelioma.

Acute febrile neutrophilic dermatosis (Sweet‐s syndrome) and myeloproliferative disorders

Acute febrile neutrophilic dermatosis (ND) consists of the abrupt onset of red, tender, cutaneous plaques on the face, extremities, and upper trunk, accompanied by fever, malaise, and neutrophilic leukocytosis. Histologically, there are distinctive, dense, dermal infiltrates of neutrophils. Response to systemic steroids is dramatic. This report describes four patients with leukemia or preleukemia and ND (LND), reviews reports of 12 similar patients, and compares LND with ND in otherwise healthy individuals (idiopathic ND, IND). Although lesions of LND more frequently had vesiculobullous appearances or location on mucous membranes, this study showed no consistent difference between LND and IND with regard to cutaneous signs, symptoms, histologic findings, and response to therapy. The first episode of LND either preceded or followed documentation of the myeloproliferative disorder, and the most common associated hematologic conditions were acute myeloid or myelomonocytic leukemia. Moderate to severe anemia was present in nine of ten patients whose first episode of LND preceded the discovery of the hematologic condition by eights months or less. The presence of anemia is the most obvious and readily detectable difference between LND and IND. The possibility of an underlying myeloproliferative disorder should be considered in all patients with ND, and LND should not be confused with infectious complications in patients known to have myeloproliferative disorders.

Malignant melanoma of the anus: report of 12 patients and analysis of 255 additional cases.

The authors present a report of 12 patients with anal melanoma (AM) and review 255 cases reported since 1947. Combining these patients with those from the literature, the authors analyze several aspects of AM that are controversial or have not been studied in a systematic manner. The mean clinical tumor size was 4.1 cm. Seventy per cent were grossly pigmented, 63 per cent were polypoid, and 44 per cent were prolapsed. Two-thirds of AM were located in the proximal pecten, at or near the level of the anal valves. Microscopically, the most useful diagnostic criteria were melanin production, junctional change, and a nesting growth pattern. In four of the authors’ cases, atypical junctional change extended laterally from the overt invasive neoplasm for distances up to 1 cm. Approximately 60 per cent of patients had metastases at the time of diagnosis. There was no statistical difference in determinate survivals of patients treated for cure by local excision and abdominoperineal resection. Neither tumor size nor configuration affected survival. The choice of therapy was not influenced by tumor size.

Sclerosing sweat duct (syringomatous) carcinoma.

ABSTRACTThis report describes 20 sclerosing adnexal carcinomas of the skin that recapitulate the sweat duct and share certain microscopic features with benign syringoma. Clinically, the neoplasms were slow-growing, indurated nodules or plaques. Sixteen were located on the face, including five on the upper lip. Three were situated in the axilla, and one involved the buttock. Twelve of the tumors (group 1) were composed primarily of cords and nests of whorled squamous cells with clear cell change and variable keratinization. Lumens consistent with ductal differentiation were few and isolated in some of these lesions, but others had more numerous and complex ducts. The remaining eight neoplasms (group 2) contained large numbers of small, uniform ducts, and exhibited little keratinization. Each neoplasm in the series infiltrated subcutaneous tissue or deeper tissues and was accompanied by sclerotic, fibrous stroma. Sixteen of the lesions (80%) exhibited perineural growth. One tumor involved an underlying lymph node, probably by direct extension. Cytologic atypicality was mild or lacking, and mitotic figures were sparse. Seven of 15 tumors (47%) with follow-up recurred, in some instances many years after primary excision. Tumor-free margins in the initial excision specimen appeared to be a favorable prognostic factor. The most aggressive lesion in the series showed increased cytologic atypicality in recurrences.

Lymphoepithelioma-like carcinoma of the skin.

Carcinomas histologically resembling nasopharyngeal lymphoepithelioma have been identified in the salivary gland, thymus, tonsil, and uterine cervix. Five patients with similar tumors primary in the skin are described. The patients ranged in age from 50 to 81 yr. Four neoplasms were situated on the head, and one was located on the shoulder. Microscopically, they were concentrated in the mid- and deep dermis and lacked connections with epidermis. The pattern was of multiple nodules, smaller irregular islands, and cords. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A lymphoid infiltrate was intimately associated with each neoplasm and obscured the malignant epithelium in one. Neither squamous nor glandular differentiation was present, but all tumors exhibited intracytoplasmic mucin. Immunohistochemistry was positive for cytokeratin (5 of 5; diffuse) and epithelial membrane antigen (4 of 5; 3 diffuse, 1 focal). Focal reactivity was also noted for carcinoembryonic antigen (1 of 5), neuron-specific enolase (1 of 5), and vimentin (1 of 5). S100 protein, leukocyte common antigen, Factor VIII-related antigen, prostate-specific antigen (males), Leu M1, and salivary amylase reactivity were absent. One patient developed local recurrence and metastases after 39 mo and was dead of disease at 57 mo. The remaining four were free of disease after 46, 27, 25, and 6 mo of follow-up. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and exclusion of occult malignancy. The tumor can be confused with a lymphoid infiltrate and is differentiated from Merkel cell carcinoma primarily on cytologic grounds. The neoplasm may be of adnexal origin.

Prognostic and therapeutic use of microstaging of cutaneous squamous cell carcinoma of the trunk and extremities

Cutaneous squamous cell carcinomas (SCC) arising in actinically damaged skin, unassociated with chronic inflammation or injury, are generally regarded as nonaggressive lesions. These tumors occasionally recur or metastasize, however, as do de novo SCC. The authors reviewed 63 patients with cutaneous SCC of the trunk or extremities, excluding lesions that developed in known high risk settings, in order to explore the potential of histologic microstaging as a prognostic indicator. Fiftyfour patients (86%) were free of recurrence following primary surgical therapy. Nine patients (14%) had either local recurrence or metastases; five of these (8% of the entire series) died of their tumors. Tumor behavior correlated best with the level of dermal invasion and the vertical tumor thickness. All tumors that recurred were 4 mm or more thick and involved the deep half of the dermis or deeper structures. All tumors that proved fatal were at least 10 mm in maximum thickness, and the four lethal lesions that could be evaluated for level of invasion extended into subcutaneous tissue or deeper structures. The thickness and level of invasion of cutaneous SCC appear to represent important prognostic factors and may be relevant indicators for wide field resection and/or elective lymph node dissection.

Intravenous pyogenic granuloma. A study of 18 cases.

A series of 18 intravenous pyogenic granulomas (IVPG) was studied. The lesions were limited to the neck and upper extremity and appeared as nonspecific tumors. Most had a clinical duration of 2 months or less. Treatment was by excision and there were no recurrences. IVPG consists of an intraluminal polyp attached to the wall of the vein by a fibrovascular stalk. The characteristic appearance is of lobules of capillaries separated by a fibromyxoid stroma. The organization and histologic detail are similar to those of pyogenic granulomas that are uncomplicated by the changes of inflammation. Our observations suggest that IVPG develops in or adjacent to the wall of the involved vein. It probably receives its blood supply from a small artery that enters the lesion in the region of the stalk.