Paul E. Swanson

Gross cystic disease fluid protein-15 as a marker for breast cancer: Immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin

The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context. In addition, GCDFP-15 was compared with another putative mammary epithelial marker, alpha-lactalbumin (ALA), with respect to sensitivity and specificity for a diagnosis of breast carcinoma. Overall, the rates of specificity and sensitivity and the predictive value of a positive result for GCDFP-15 were 95%, 74%, and 74%, respectively. Corresponding statistical parameters for ALA were 50%, 50%, and 23%. A consistent congruency between the reactivity patterns of primary and metastatic breast cancers was noted for GCDFP-15 but not for ALA. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were carcinomas of the salivary glands, sweat glands, and prostate. Since the latter three types of lesions are unlikely to be diagnosed as metastatic breast cancer, statistical indices were recalculated after exclusion of these three tumor types. Following this exclusion, the adjusted rate of specificity of GCDFP-15 and the predictive value of a positive result for a diagnosis of metastatic carcinoma of the breast were each 99%. In contrast, predictive parameters for ALA were not altered. These results show that GCDFP-15 is a specific marker for breast cancer and is superior to ALA in this respect.

Recognition of malignant melanoma by monoclonal antibody HMB‐45. An immunohistochemical study of 200 paraffin‐embedded cutaneous tumors

Antibodies to S‐100 protein have been used widely as markers of malignant melanoma, despite abundant evidence that they are non‐specific for this neoplasm. Hence, alternatives to these reagents are desirable in diagnostic dermatopathology. We evaluated the characteristics of a new monoclonal antibody (HMB‐45) which does have putative specificity for melanoma, and compared it with a polyclonal anti‐S‐100 reagent in immunohistochemical staining of 67 melanomas of the skin and 133 non‐melanomatous cutaneous neoplasms. All specimens were formalin‐fixed and paraffin‐embedded, and were studied with the avidin‐biotin‐peroxidase complex technique. HMB‐45 labelled 62 of 67 melanomas, while anti‐S‐100 recognized all tumors of this type. On the other hand, S‐100 also was expressed by 15 of the non‐melanocytic neoplasms, all 133 of which were HMB‐45‐negative. The only cases of melanoma that were missed by the latter reagent were of the spindle‐cell type. Hence, HBM‐45 was 100% specific and 93% sensitive, relative to a diagnosis of malignant melanoma in paraffin sections. Epithelioid and small‐cell neoplasms are reliably recognized by this antibody, but it would appear that spindle‐cell melanomas must be detected by other immunohistochemical means.

Primary cutaneous leiomyosarcoma. A histological and immunohistochemical study of 9 cases, with ultrastructural correlation

Leiomyosarcoma (LMS) of dermal and subcutaneous tissues is an uncommon neoplasm. In order to analyze the specialized pathologic features of this tumor, we undertook a histological, ultrastructural, and immunohistochemical study of 9 superficial LMS, including 7 dermal lesions and 2 subcutaneous neoplasms. These were compared with 12 examples of “deep” extracutane‐ous LMS. Metastases to the skin from two of the latter neoplasms were also examined. Immunohistochemistry was found to be a useful diagnostic adjunct to light microscopic and ultrastructural studies in that all LMS coexpressed vimentin and des‐min, regardless of site, and 90% also expressed muscle‐specific actin. Variable expression of cathepsin B and niyelin basic protein was noted in 8 and 10 tumors, respectively, whereas none contained cytokeratin. Weak cytoplasmic positivity for epithelial membrane antigen was seen in 1 dermal and 3 extracutaneous LMS. Of 7 dermal LMS, 4 contained S‐100 protein, whereas this determinant was found in only 1 of 12 extracutaneous tumors. Conversely, Leu 7 reactivity was present in 7 of 12 extracutaneous LMS, but only 2 of 9 superficial lesions. Review of clinical features confirmed that subcutaneous LMS is capable of aggressive behaviour, whereas dermal LMS was more likely to behave in an indolent fashion. However, one example of dermal LMS exhibited aggressive local recurrences and distant metastasis, ultimately leading to the death of the patient. Therefore, careful clinical followup is indicated in all cases.

Malignant rhabdoid tumor of the vulva: is distinction from epithelioid sarcoma possible? A pathologic and immunohistochemical study.

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors—ours and the few published examples of ES—is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.

Neuroendocrine differentiation in basal cell carcinoma. An immunohistochemical study

Neuroendocrine differentiation in basal cell carcinoma (BCC) of the skin has been reported in the past on the basis of ultrastructural findings, argyrophilia, and the immunohistochemical detection of neuropeptides in such neoplasms. To assess further the relative frequency of neuroendocrine differentiation in BCC, paraffin sections of 53 randomly chosen cases were evaluated for Churukian–Schenk stain positivity and the expression of sensitive neuroendocrine markers. These included neuron-specific enolase (using a highly absorbed monospecific antiserum), chromogranin-A, synaptophysin, neurofilament protein, and Leu-7 antigen. Although 25% of cases demonstrated argyrophilia with the Churukian–Schenk method, suggesting a high frequency of possible neuroendocrine differentiation, immunohistochemical evidence of the same was observed in only two tumors (4%). These demonstrated immunoreactivity for chromogranin and neuron-specific enolase. The results of this analysis suggest that neuroendocrine differentiation in BCC is relatively uncommon, and that it is not reliably predicted by the results of argyrophil stains done on paraffin sections.