Adenomatoid tumors of the pleura.

We report two cases of small pleural nodules showing the distinctive histologic appearance of adenomatoid tumor. Both lesions were discovered incidentally during surgery in patients undergoing lung resection for unrelated intrapulmonary masses: lung carcinoma in one case and histoplasmosis in the other. The tumors were composed of a focal proliferation of epithelioid cells forming vacuoles and tubular spaces in a fibrous stroma, as seen in adenomatoid tumors from other sites. The differential diagnosis in both cases included metastatic signet ring cell carcinoma. The mesothelial nature of the lesions was supported by immunohistochemical and ultrastructural evidence. The tumor cells in both cases were positive for cytokeratin but negative for carcinoembryonic antigen and LeuM1. One case was also negative for BER-EP4, B72.3, CD34, and Factor VIII. Electron microscopy in this case demonstrated well-developed basal laminae, desmosomes, and numerous slender microvilli along the luminal surfaces of the tumor cells. Adenomatoid tumors are regarded as a benign variant of mesothelioma. Despite the abundance of mesothelial cells in the pleura, adenomatoid tumors are apparently extremely rare in this location. Separation from malignant lesions such as adenocarcinoma and epithelioid hemangioendothelioma is important.

Parotid involvement by desmoplastic melanoma.

Desmoplastic malignant melanoma often arises in sun damaged skin of the head and neck and shows frequent neurotropism. Although metastatic melanoma frequently involve the parotid, direct spread to the parotid has been rarely reported. We evaluated five cases of desmoplastic malignant melanoma involving the parotid gland with clinical and pathological evidence of precursor cutaneous lesions in four of the five cases. The parotid involvement in four cases was tumoural, and three of these were not clinically suspected to be melanoma. The histological appearance in all five cases was that of a sarcomatoid tumour. Immunohistochemistry and electronmicroscopy performed on three of the cases showed only evidence of schwannian differentiation: the tumour cells were positive for S-100 protein and vimentin, and negative for cytokeratin and HMB-45. Electronmicroscopy showed no evidence of melanogenesis. All five tumours showed histological evidence of prominent neurotropism with one case demonstrating extension from overlying skin along cutaneous nerves to the superficial parotid. Thus, desmoplastic malignant melanoma may involve the parotid by neurotropic spread and can be pathologically indistinguishable from malignant schwannoma, a diagnosis which may be made erroneously in the absence of clinical information.

ras and p53 genes in male breast cancer.

We have studied the roles of Ki-ras oncogene and p53 tumor suppressor gene in a series of 20 cases of male breast cancer and one papilloma of the male breast. Ki-ras was detected in 50-microns sections after digestion with proteinase K and SDS. DNA was amplified by polymerase chain reaction, dot blotted, and mutations were screened with labeled ras mutation-specific oligonucleotides. Wild-type and mutant p53 protein were detected with antibodies CM1 and DO7, using the avidin-biotin-peroxidase method. Two of 17 carcinomas showed Ki-ras mutations, both in codon 12 (gly --> lys and gly --> arg). Five of 20 male breast cancers (25%), including one large intraductal carcinoma, expressed mutant p53 protein. Although the incidence of mutant p53 expression in male breast cancer is similar to that in women, Ki-ras mutations are not significantly increased.

Immunohistochemical assessment of tumor vascularity in recurrent Clark II melanomas using antibody to type IV collagen.

Thin melanomas, measuring 0.76 mm or less, are generally associated with an excellent prognosis. However, a certain subset of these seemingly innocuous lesions have been reported to develop recurrences. Therefore, the predictive values of currently accepted prognostic indicators have been questioned in thin melanomas. Several studies concerning tumor vascularity in melanoma and certain non-melanocytic malignancies suggest that the degree of vascularization correlates with growth rate and biologic aggressiveness. In the present study, we determined the vascularity of a small group of Clark level II melanomas that resulted in recurrence, and compared these results to an equal number of nonrecurrent lesions with similar prognostic indicators. Blood vessels were labeled by immunoperoxidase staining techniques for Type IV collagen, and quantified by image analysis. No statistical difference was found between the two groups when mean blood vessel counts and percent vascular area were measured. The recurrent tumors had a mean PVA of 4.68 compared to 4.34 for the nonrecurrent group (p = 0.677). The mean blood vessel count beneath the recurrent group was 29.6 per 400 x field, and the corresponding value for the nonrecurrent group was 31.8 (p = 0.681). Our data is preliminary within this limited group of tumors, yet it suggests that tumor vascularity is not a distinctive prognostic indicator by which eventual outcome can be predicted in thin Clark level II malignant melanomas.

Histopathologic study of recurrent Clark level II melanomas.

Overall, the prognosis for thin lesions of melanoma (less than 0.76 mm) is excellent. However, a number of melanoma patients with seemingly innocuous lesions have been reported to develop recurrences. For this reason, we examined histologic sections taken from eight cases of Clark level II melanoma that unexpectedly recurred, and compared their histopathologic features with an equal number of nonrecurrent lesions in whom reliable clinical follow-up data were available. Prognostic variables including Breslow thickness, mitotic rate, ulceration, the presence or absence of regression, a vertical growth phase component, and an associated banal nevus were evaluated in a double blind manner. When attempts were made to predict outcome based on one or more prognostic variables, the only correlation of statistical significance was the Breslow thickness (P = 0.04). A Breslow thickness greater than 0.4 mm was associated with a significantly shorter disease free interval than a thickness below 0.4 mm. There was no significant correlation between predicted outcome based on the histologic features examined and the eventual outcome based on history of recurrence (P = 0.36). These data indicate that although prognostic models that predict outcome in melanoma are generally reliable, there is a sizable population of patients with thin melanomas that do worse than would be expected.

Etiology and prognosis of local recurrence in malignant melanoma of the skin.

All patients with stage I and stage II malignant melanoma of the skin were analyzed for stage; time of local, regional, or systemic recurrence, or two or more of these events; presence or absence of ulceration of the primary tumor; thickness of the primary tumor; level of invasion according to Clark; and margins of resection. Local recurrence had a significant negative impact on the long-term survival of patients. Our data revealed that local recurrence had the same poor prognostic effect as regional or systemic recurrence, or both. Factors significant in predicting local recurrence included the primary tumor characteristics of ulceration of the primary tumor and thickness of the primary tumor. Margins of resection and level of invasion were not noted significant in predicting local recurrence.

Monoclonal antibodies against glycophorin A.

Two mouse IgM monoclonal antibodies, 177.1 and 179.3, are directed against glycophorin A, the major sialoglycoprotein of human erythrocytes. Both antibodies agglutinate blood group M and N erythrocytes equally well, both before and after treatment with neuraminidase or trypsin, but fail to agglutinate erythrocytes treated with papain. Antibody 179.3 agglutinates MiVII(K.T.) cells, whose glycophorin A probably contains some alterations in amino acid sequence between residues 46-56, but antibody 177.1 does not agglutinate these cells. Neither antibody agglutinates En(a-)G.W. cells, which lack glycophorin A completely. The hemagglutinating activity of antibody 177.1 is inhibited by purified glycophorin A and its chymotryptic glycopeptides CH1 (amino acid residues 1-64) and CH3 (amino acid residues 35-64), whereas the hemagglutinating activity of 179.3 is inhibited weakly by glycophorin A but not by chymotryptic peptides. These antibodies both are classified as anti-En(a-)FS but apparently bind different epitopes.

Study of the idiotypy of lipopolysaccharide-specific polyclonal and monoclonal antibodies.

The monoclonal antibodies produced by a variety of hybridomas making antibody specific for E. coli 0113 lipopolysaccharide (LPS) were purified by affinity chromatography and their fine specificity studied. All reacted specifically with the polysaccharide moiety of LPS from E. coli 0113 and from Neisseria lactamica; two reacted with LPS from Pseudomonas aeruginosa and one reacted with LPS from Klebsiella pneumoniae. Polyclonal and monoclonal syngeneic and semi-syngeneic anti-idiotypic antisera were produced to study the idiotypy of LPS-specific monoclonal antibodies which express a complex cross-reactive idiotype (IdX) as well as individual idiotypes. E. coli 0113 LPS-specific antibodies produced by BALB/c mice express this IdX and the kinetics for its expression was examined using mice either primed or hyperimmunized with LPS; idiotypic maturation was observed, but we were unable to detect an auto-anti-idiotypic antibody response. This IdX was expressed on E. coli 0113 LPS-specific antibodies from all strains of mice examined, indicating that its expression is not restricted by genes linked to the IgCH locus.

Generation of anti-type III pneumococcal polysaccharide hybridomas from mice with an X-linked B-lymphocyte defect.

(CBA/N X BALB/c male)F1 mice bear on X-linked defect making them totally unresponsive to T-independent (TI), TI-2 antigens such as type III pneumococcal polysaccharide (SSS-III). We found that somatic cell hybrids between CB nonresponder spleen cells and NS1 plasmacytoma cells secreted antibody specific for SSS-III. The solid-phase binding of such antibody was completely inhibited by the addition of free antigen (SSS-III) and the amount of antibody detected in culture fluids ranged from 10 ng/ml to 10 micrograms/ml. Eight hybridoma clones were identified; all make antibody of the IgM class. These results indicate that the X-linked defect does not result in a deletion of a B-cell subset which responds to TI-2 antigens.

Atypical hyperplasia of lymph nodes: a follow-up study.

Atypical hyperplasia of lymph nodes (AH) is neither a clinical nor a pathologic entity but represents cases in which the pathologist expresses concern about neoplasia and is unable to diagnose lymphoma. We reviewed 70 cases of AH diagnosed over the years 1961-1972. Thirty-seven percent developed a malignant lymphoproliferative disease during a follow-up that varied from 2-13 years. When the cases were histologically reexamined without knowledge of their clinical outcome or initial clinical features, 19 were diagnosed as benign, 10 as malignant, 37 as AH, and 4 as angioimmunoblastic lymphadenopathy. None of the patients of the first group developed a malignant lymphoma, but lymphoma occurred in 30% of the AH group. This latter group was divided into two subgroups according to the expectation of the course of disease; those with a probably malignant course and those with a probably benign course. Malignant lymphoma developed in 8 (73%) of the 11 patients in the first group but in only 14% of the 26 patients in the second group. It appears that although the pathologist can rather well appreciate the probable development of malignant lymphoma in AH cases, he is wrong too often--in this series 16%. Therefore, the common practice of designating a suspicious lymph node biopsy as atypical hyperplasia with a request for a later repeat biopsy is recommended.