James H. Graham

Merkel cell carcinoma: Analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival

BACKGROUND Merkel cell carcinoma (MCC) is an uncommon malignancy of the skin and has a high rate of recurrence and metastasis. There have been few large studies of the biologic behavior of MCC. OBJECTIVE Our purpose was to determine whether there were clinical or histologic features of MCC that predict its biologic behavior. METHODS We reviewed 132 cases of MCC. Clinical and histologic features were correlated with follow-up information to determine whether any of these were associated with prognosis. RESULTS Clinical information was available on 126 patients; 57 were alive, 1 was alive with tumor, 28 died of tumor, 27 died from other causes, and 14 were lost to follow-up. MCC on the buttock/thigh area or trunk had the worst prognosis, and those on the distal extremities had the best prognosis; however, the difference was not statistically significant. Sex and age were not significant factors. Small cell size, high mitotic rate, and large tumor size were associated with a low survival rate. When cell size was excluded, male sex and depth of invasion were associated with a worse survival, although these were not statistically significant. CONCLUSION Cell size, mitotic rate, and tumor size are significant factors in relation to the biologic behavior of MCC.

Spindle Cell and Epithelioid Cell Nevi with Atypia and Metastasis (malignant Spitz Nevus)

We report on the clinical and pathologic features of 32 lesions diagnosed as malignant spindle cell and epithelioid cell nevus (S&E nevus). Because of the clinical or initial histopathologic diagnosis of malignant melanoma, six patients had lymph node dissection. Three of these patients also had an enlarged lymph node. In all six cases, metastatic spindle or epithelioid cells were found in at least one of the resected lymph nodes. Of the 30 patients with follow-up information, including all six patients with lymph node metastases, all are alive and well. No recurrences or further metastases have been found. On histopathologic reevaluation, all the lesions had features of S&E nevi. Study of these cases suggests that although some lesions with features of S&E nevi may involve local lymph nodes, widespread metastases do not result.

Hmb-45 Staining in Benign and Malignant Melanocytic Lesions: A Reflection of Cellular Activation

The antibody HMB-45 used as an immunohistochemical reagent has often been labeled as a marker for melanoma, even though some benign lesions have been noted to show positive staining reactions with this reagent. Biopsy specimens from 225 benign and malignant melanocytic lesions were examined after immunoperoxidase staining for S-100 protein and HMB-45. The lesions studied included common acquired nevi, spindle cell and epithelioid cell nevi (Spitz nevi), cellular blue nevi, deep penetrating nevi, congenital nevi, nevi from hormonally reactive areas (genital), malignant melanoma, and desmoplastic malignant melanoma. A positive reaction for HMB-45 was seen in the dermal component in a high percentage of each of these types of lesions except for the common acquired nevi and the desmoplastic malignant melanomas that were uniformly negative for HMB-45 in the dermal component. HMB-45 correlates with melanosome production and thus a melanocytic origin of HMB-45-positive cells. HMB-45 may correlate best with factors that stimulate melanocytic proliferation and production of melanosomes.

Deep penetrating nevus

We report a clinical and histologic study of 70 patients, each with a single melanocytic lesion termed “deep penetrating nevus” (DPN). The lesions are most commonly found on the face, upper trunk, or proximal extremities of patients between the ages of 10 and 30 years. Typically they are darkly pigmented. Histologically they are characterized by loosely organized nests of pleomorphic pigmented cells that penetrate deep into the reticular dermis and often to the subcutaneous fat. Follow-up was obtained from 48 patients. It ranged from 1 to 23 years (mean, 7 years). Despite an initial histologic diagnosis of malignant melanoma in 29% of the cases, there were no local recurrences and no distant metastases. It is important to differentiate DPN from malignant melanoma. The characteristic histologic features of DPN also allow its differentiation from spindle cell and epithelioid cell nevi and blue nevi.

Proliferating epithelial cysts : clinicopathological analysis of 96 cases

Ninety‐six proliferating cutaneous epithelial cysts were classified into two subtypes, proliferating trichilemmal cysts (PTC) and proliferating epidermoid cysts (PEC), depending on the mode of keratinization or the origin of the tumors. The clinicopathological features and the biological behavior of these two subtypes were compared. Among 63 patients with PTC, 45 (71%) were women and 18 (29%) were men. The most common site was the scalp (78%), followed by the trunk (13%). These tumors were well circumscribed subepidermal lesions and demonstrated uniform histologic pattern with varying degrees of cytologic atypia. A few tumors extended into the epidermis and occasionally became ulcerated. Follow‐up of 59 (94%) PTC for an average of 4 years revealed recurrence in one. Ten tumors demonstrated carcinomatous changes including one with anaplastic carcinoma and regional lymph node metastasis. None of these tumors recurred or developed further metastasis following wide excision. Of 33 PECs, 12 (36%) occurred in women and 21 (64%) in men. These tumors were widely distributed in the pelvic and anogenital areas (36%), followed by the scalp (21%), upper extremities (18%), and trunk (15%). Seventy‐nine percent of the PECs were located in areas outside the scalp. The PECs were subepidermal tumors but often communicated to the surface. The histologic pattern of PEC was more variable than that of PTC. Seven tumors exhibited carcinomatous changes. Follow‐up of 30 (91 %) PEC revealed local recurrences in 6, with multiple recurrences in 3, and extensive local invasion in 2, resulting in death in one. Greater anaplasia, high mitotic rate and deeper invasion were associated with increased incidence of recurrence and aggressive behavior. Although both PTC and PEC were locally aggressive tumors and potentially malignant, distant metastasis was unusual. These tumors should be treated with wide local excision, especially those showing cytologic atypia and carcinomatous changes.

Arteriovenous hemangioma (arteriovenous shunt). A clinicopathological and histochemical study

Sixty‐nine patients with predominantly asymplomatic solitary angiomatous lesions were studied. Lips and perioral skin were the usual location, and the lesion occurred almost exclusively in adults. The essential histopathologic features are multiple dilated vascular channels located in the corium or submucosa and without significant epidermal participation. Anastomosing vascular spaces are lined by endothelial cells and thin‐walled veins contrast sharply with arteries showing thick fibromuscular walls. The pathogenesis of these peculiar hemangiomas is unknown, but they probably represent hamartomas with numerous arteriovenous shunts and arise from the subpapillary vascular plexus. Simple surgical excision is curative and represents the treatment of choice. The term of arteriovenous hemangioma is proposed for this clinicopathologic entity and should be considered in the differential diagnosis of other acquired benign hemangiomas and vascular lesions occurring in middle‐aged patients.

Primary cutaneous adenoid cystic carcinoma

Primary adenoid cystic carcinoma of the skin is rare. Ten cases from the files of the Armed Forces Institute of Pathology were studied. Seven of the 10 cases recurred after initial surgery. The interval between surgery and recurrence ranged from 4 months to 20 years. In one case there was metastasis to lung and pleura. Histologically, cutaneous adenoid cystic carcinoma is indistinguishable from adenoid cystic carcinoma of the salivary gland. The diagnostic histologic features and the differentiation of adenoid cystic carcinoma from other cutaneous neoplasms are discussed.

Pigmented spindle cell nevus: A clinicopathologic analysis of ninety-five cases†

BACKGROUND Pigmented spindle cell nevus (PSCN) is often interpreted as a Spitz nevus or misdiagnosed as malignant melanoma. OBJECTIVE The purpose of this study was to analyze the clinical and histologic features and to determine the biologic behavior of 95 cases of PSCN. METHODS We reviewed clinical data, follow-up information, and microscopic features of all 95 cases of PSCN. RESULTS PSCNs are dark brown to black, 3 to 6 mm in diameter, and occur most commonly on the extremities (75%) and back (16%) with a predilection for the legs. These lesions are more common in women in the third decade of life. Microscopically, PSCNs are characterized by uniform, spindle-shaped, pigmented melanocytes. Although some histologic features overlap with those in spindle and epithelioid cell nevus, PSCN is a separate entity. In addition, PSCN must be differentiated from malignant melanoma. Fifty-seven patients (60%) observed for an average of 6 years did not develop local recurrence or metastasis. CONCLUSION PSCN is a distinctive, acquired, benign melanocytic lesion, that should not be confused with spindle and epithelioid cell nevus or malignant melanoma. Complete excision is recommended for treatment.

Trichogerminoma. Report of 14 cases.

We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasm occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudo‐encapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or “cell balls” resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice.

HMB45 negative spindle cell malignant melanoma.

Desmoplastic malignant melanoma (DMM) and spindle cell malignant melanoma (SCMM) form a continuum without a discrete separation. One feature characteristic of DMM is a negative reaction for HMB45, a marker for premelanosomes. Fifty-six cases of SCMM were stained with HMB45. The clinical features, histologic features, and survival data for HMB45(+) and HMB45(-) SCMM were compared. Thirty cases were HMB45(-), and 26 were HMB45(+). In the HMB45(-) cases, there was a 1.4:1 ratio of males to females, and in the HMB45(+) cases the ratio was 1:1.5. Only 12.9% of the HMB45(-) cases occurred on the trunk compared with 40% of the HMB45(+) cases. The average ages for the HMB45(-) and the HMB45(+) cases were 65.6 and 61 years, respectively. Follow-up was obtained on 22 cases: 11 HMB45(-) and 11 HMB45(+). Of the 11 HMB45(-) cases, four had a 5-year disease-free survival. Of the 11 HMB45(+) cases, only one had a 5-year disease free survival. HMB45(-) SCMM appear to have a less aggressive biologic potential than HMB45(+) SCMM.