Michael S. Rabkin

Atypical Spitz nevi/tumors : Lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues. In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria. For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free. Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review. Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma. These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi*

BACKGROUND Nevi that are clinically atypical and histologically dysplastic have been associated with increased melanoma risk. There are few reproducibility studies or population-based studies of nevus histology. OBJECTIVE Our purpose was to quantify concordance in histologic diagnosis of melanocytic lesions among a diverse group of pathologists, to assess intraobserver concordance by comparing readings of the same slide as well as of adjacent recuts from the same block, to correlate histology with nevus appearance and melanoma risk, and to estimate the range of prevalence of histologic dysplasia. METHODS Histologic slides were prepared from 149 tissue blocks of pigmented lesions from melanoma cases, relatives, and controls. Six dermatopathologists independently evaluated the lesions for histologic dysplasia, without prior agreement on criteria. RESULTS According to kappa statistics, intraobserver reproducibility was substantial, and interobserver concordance was fair, despite differences in criteria. The estimated prevalences of histologic dysplasia for the six pathologists ranged from 7% to 32%. Histologic dysplasia was correlated with nevus size for most observers, confounding the observed correlation between nevus appearance and histology. CONCLUSION Although experienced dermatopathologists use different diagnostic criteria for histologic dysplasia, their usage is consistent. Histologic changes ascribed to melanocytic dysplasia are prevalent in the white population for all pathologists. The term nevus with histologic dysplasia should be used in preference to dysplastic nevus.

The utility of cytokeratin 5/6 in the recognition of cutaneous spindle cell squamous cell carcinoma

Background: Cutaneous spindle cell squamous cell carcinoma (SSCC) is a challenging diagnosis since it may be difficult to distinguish from spindle cell melanoma, leiomyosarcoma and atypical fibroxanthoma. Furthermore, it may be difficult to demonstrate epithelial differentiation by a traditional immunohistochemical panel. We performed an expanded immunohistochemical evaluation of ultrastructurally documented SSCC to assess its utility in diagnosing this entity.

Dysplastic naevi with moderate to severe histological dysplasia : a risk factor for melanoma

Background  The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.

Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up

Predicting clinical behavior of atypical Spitz tumors remains problematic. In this study, we assessed interobserver agreement of diagnosis by 13 expert dermatopathologists for atypical Spitz tumors (n=75). We determined which histomorphologic features were most heavily weighted for their diagnostic significance by the experts and also which histomorphologic features had a statistically significant correlation with clinical outcome. There was a low interobserver agreement among the experts in categorizing lesions as malignant versus nonmalignant (&kgr;=0.30). The histomorphologic features that were given the most diagnostic significance by the experts were: consumption of the epidermis, atypical mitoses, high-grade cytologic atypia, and mitotic rate. Conversely, the histomorphologic features that most correlated with disease progression were: frequent mitoses, deep mitoses, asymmetry, high-grade cytologic atypia, and ulceration. The presence and/or pattern of pagetoid spread, consumption of the epidermis, and lymphoid aggregates demonstrated no association with clinical behavior. The results support the assertion that there is a lack of consensus in the assessment of atypical Spitz tumors by expert dermatopathologists. Importantly, many features used to distinguish conventional melanoma from nevi were not useful in predicting the behavior of atypical Spitz tumors. This study may provide some guidance regarding histologic assessment of these enigmatic tumors.

Analysis of therapeutic and immunologic effects of R24 anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma

Antitumor effects of antibodies against ganglioside antigens of melanoma have been reported, but neither optimal doses nor mechanisms have been established.

Clinical, ultrastructural immunohistochemical and DNA content analysis of lymphomas having features of interdigitating reticulum cells

Interdigitating reticulum cells (IRC) are dendritic, nonphagocytic histiocytes found in thymus‐dependent areas of lymphoid tissues. We report two cases of large cell lymphoma having features of IRC in patients 13 and 17 years old. In each case the diagnosis was suggested by light and electron microscopic features, positive immunoperoxidase staining for S‐100 protein, and additional immunoperoxidase findings. Both patients presented with aggressive lymphomas and were treated with intensive combination chemotherapy. Each patient achieved a complete clinical remission, then rapidly relapsed and died with disseminated disease 3 and 9 months after presentation. Novel findings included strong staining of specimens with an antibody to epithelial membrane antigen, staining of one specimen with peanut agglutinin in the pattern previously described in normal IRC, and a DNA content analysis that showed aneuploid stem cell lines in both patients.

Mid-dermal elastolysis with inflammation

A 71-year-old white woman had finely wrinkled, erythematous patches of skin that met the clinical and histologic criteria for mid-dermal elastolysis. In addition to the loss of mid-dermal elastin described in previous cases, histopathologic examination revealed a superficial and deep perivascular inflammatory infiltrate of lymphocytes and plasma cells and interstitial collections of multinucleated giant cells containing phagocytized elastin. These results support a previously postulated inflammatory pathogenesis for mid-dermal elastolysis.

Histopathologic characteristics of dysplastic nevi: Limited association of conventional histologic criteria with melanoma risk group

Studies of dysplastic melanocytic nevi (DMN) have suggested that lesions from patients with a personal or family history of malignant melanoma are histologically more atypical than are those from control populations without such histories. To evaluate this possibility, we examined histologic sections of DMN that had been removed from patients in three groups. Group A consisted of 17 subjects with a past history of melanoma; group B comprised 79 subjects with DMN and a family history of melanoma in first-degree relatives; group C consisted of 64 subjects who were unrelated spouses of members of groups A and B. For each group, sections of DMN were initially selected on the basis of architectural atypia as defined by the National Institutes of Health Consensus Conference. All biopsy material was then further evaluated for four histologic features suggested to be discriminatory for DMN associated with increased melanoma risk; the features are degree of junctional activity, irregularity of melanocytic nests, presence of dusty melanin, and size of melanocytic nuclei. A subjective rating was given for each on a 0 to 3 scale of increasing severity. Three pathologists individually rated the specimens without knowledge of the patient group. The means of the individual observer cumulative scores of the four histologic criteria for each biopsy specimen and the average of these means from the three observers exhibited a trend to increasing values from groups C to A, but none of the differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow cytometric DNA content analysis of a case of pilomatrix carcinoma showing multiple recurrences and invasion of the cranial vault.

Pilomatrix carcinomas are rare neoplasms of the skin that may be locally aggressive or metastatic. The differentiation of these tumors from benign pilomatrixomas depends on a constellation of microscopic features, some of which may be equivocal or absent in individual biopsy specimens. We encountered a tumor with distinct pilomatrix differentiation (lobulated nests of basaloid cells, ghost cells, focal calcification) that recurred multiple times and ultimately invaded the cranial vault. Despite this aggressive behavior, the tumor was difficult to separate from benign pilomatrixoma on morphologic grounds. Because DNA content flow cytometry has proved useful in the prediction of aggressive behavior in various solid tumors, we analyzed this neoplasm by flow cytometry. Neither aneuploid peaks nor a high proliferative fraction were seen in this example of pilomatrix carcinoma.