CONTEXTCadherins are cell-cell adhesion proteins that act as tumor suppressor genes and have a critical role in cell sorting and tissue formation during organogenesis. The pattern of cadherin expression constitutes a useful diagnostic and prognostic tool in the evaluation of tumors and for determining the histogenesis of tumor cells. We have previously characterized the cell types of several tumors based on the expression of individual cadherins.OBJECTIVETo investigate the expression of cadherins in Merkel cell carcinomas.DESIGNParaffin immunohistochemical analysis of the 3 best-studied cadherins was performed on 35 cases of Merkel cell carcinoma.RESULTSE-cadherin was expressed in 34 (97%) of 35 Merkel cell carcinomas examined, N-cadherin was expressed in 22 (63%) of 35 cases, and P-cadherin was expressed in 15 (43%) of 35 cases. This frequency of cadherin expression was similar to a group of small cell and neuroendocrine tumors from other primary sites. Interestingly, the localization of E-cadherin expression was unique in Merkel cell carcinomas compared with other primary neuroendocrine tumors. Merkel cell carcinomas showed marked preference for nuclear versus membrane localization, whereas small cell tumors from other sites showed fewer cases of nuclear E-cadherin expression. The nuclear localization of E-cadherin did not correlate with cadherin-associated protein beta-catenin nuclear expression.CONCLUSIONSOur findings show that E-cadherin is the most frequently expressed cadherin in Merkel cell carcinoma, followed in frequency by N-cadherin then P-cadherin. The pattern of nuclear E-cadherin expression is more frequent for Merkel cell carcinoma than small cell tumors of other primary sites. These observations suggest that E-cadherin expression and function are altered in Merkel cell carcinoma, and this finding has potential use in the differential diagnosis of these tumors.

The International Society of Gynecological Pathologists was founded in 1976 to facilitate an exchange of knowledge about gynecological disease throughout the world. The Society moved quickly to schedule companion meetings with established international and regional pathology and gynecology societies, including the International Academy of Pathology, its United States-Canadian Division, and the International Federation of Gynecology and Obstetrics, and to sponsor smaller meetings within individual countries. In 1981 the Society founded this journal, and in 1983, at the invitation of the World Health Organization, it assumed the responsibility of revising the WHO classifications of tumors of the female genital tract. The foundation of the Society appears to have been solid in view of its present robust health.

The cadherins are homotypic adhesion proteins that are important in cell sorting during organogenesis. Classical cadherins include several different types that show tissue-specific expression. Cell lineage-specific expression of different cadherin subtypes can differentiate morphologically similar but histogenetically distinct tumors. We examined by immunohistochemistry in paraffin sections, the expression of E (epithelial), N- (neural), and P- (placental) cadherin in 36 unusual tumors of the breast (22 medullary carcinomas, 5 metaplastic carcinomas, 2 carcinosarcomas, 4 phyllodes tumors, and 3 periductal stromal tumors). All carcinomas stain with E-cadherin (22 of 22 medullary and 5 of 5 metaplastic). E-cadherin also stained the epithelial component but not the sarcomatous areas of 2 of 2 cases of carcinosarcomas. E-cadherin was not detected in the stromal tumors (phyllodes, periductal stromal tumor). N-cadherin was most frequently expressed in sarcomatoid metaplastic carcinomas (5 of 5), and variably in other tumors, including the sarcomatous area of carcinosarcoma (1 of 2), and 6 of 22 medullary carcinomas. P-cadherin was frequently identified in medullary carcinomas (20 of 22), in 5 of 5 metaplastic carcinomas, and in the proliferating stroma and benign epithelium of 3 of 3 periductal stromal, but not in phyllodes tumors (0 of 4). All sarcomatoid metaplastic carcinomas co-expressed all 3 classical cadherins. Our results show that these breast tumors have unique patterns of cadherin expression suggesting different histogenetic origin or lines of differentiation. The cadherin profiles in these tumors may be useful for classification and diagnosis.

BACKGROUNDbeta-tubulin, the intracellular target of several antimicrotubule agents, is encoded by at least six genes and exists as multiple isotypes with tissue-specific expression. Previous in vitro studies indicated that tubulin isotype composition may affect polymerization properties, dynamics, and sensitivity to drugs.METHODSTo investigate the isotype composition of beta-tubulin in human prostate, tissues were collected from 26 patients after radical prostatectomy and sections were stained with isotype-specific antibodies.RESULTSbeta IV tubulin is the predominant isotype in benign prostatic hyperplasia (BPH) and adenocarcinoma, showing significantly stronger immunohistochemical expression than beta II and beta III, particularly in Gleason's grade 3 and 4 cancers. Staining for the beta II isotype was invariably weak and often absent in BPH and normal glands. There was a marked increase in beta II isotype stain from BPH to cancer in 77% of the patients, suggesting that the expression of this isotype is related to malignant status.CONCLUSIONSThe beta II tubulin isotype is a potential marker for prostate adenocarcinoma. The possibility that tumor beta-tubulin isotype composition may effect the response to antimicrotubule drug therapy in prostate cancer and other tumors merit investigation.

The differential diagnosis of pleural mesotheliomas and lung adenocarcinomas presents a continued challenge in the practice of surgical pathology. Paraffin immunohistochemistry (IHC) using different panels of antibodies can be helpful in some cases, but, as yet, no antigen is expressed specifically in mesotheliomas nor in adenocarcinomas. Using well characterized monoclonal antibodies (MAb) that recognized distinct mesenchymal and epithelial adhesion proteins, N-cadherin (13A9 MAb) and E-cadherin (E9 MAb), respectively, we found previously that in frozen-section IHC mesotheliomas and adenocarcinomas had distinct cadherin phenotypes: mesotheliomas were positive for N-cadherin, and lung adenocarcinomas were positive for E-cadherin. Using antigen-retrieval methods, we successfully extended our study to formalin-fixed, paraffin-embedded tissue sections. Tumors from 28 patients (14 originally diagnosed as mesotheliomas, and 14 diagnosed as adenocarcinomas) were stained with 13A9 MAb and E9 MAb. Review of hematoxylin-eosin sections excluded from analysis one case previously diagnosed as mesothelioma, which represented a hemangiopericytoma. Of the remaining 27 cases, 12 of 13 mesotheliomas were positive for N-cadherin and negative for E-cadherin. The exception was a multifocal microscopic papillary tumor of apparent mesothelial origin, which was negative for both N-cadherin and E-cadherin. Conversely, 13 of 14 adenocarcinomas were E-cadherin positive and N-cadherin negative except for one adenocarcinoma with focal N-cadherin expression. One case of a poorly differentiated adenocarcinoma invading skeletal muscle was negative for both 13A9 and E9. These studies confirmed the utility of the cadherin antibodies in distinguishing pleural mesotheliomas from lung adenocarcinomas. The reactivity of the cadherin-specific antibodies with antigens in paraffin sections make them powerful and reliable markers in the practice of diagnostic surgical pathology.

The role of chemotherapy (CTX) in the treatment of localized adenocarcinoma of the pancreas must be enhanced if current results are to be surpassed. It is postulated that histologic response to various chemotherapeutic agents may offer an assessable endpoint intermediate to and perhaps as or more meaningful than survival analysis.

BACKGROUND: We hypothesized that delivering adjuvant radiotherapy (RT) preoperatively with chemotherapy might enhance local control of the cancer and patient tolerance for the intervention.METHODS: Thirty-four patients with localized pancreatic cancer (24 head, 8 head and body, 2 body and tail) were treated during the past 6 years with an intramural protocol consisting of 5-fluorouracil (1,000 mg/m(2) on days 2 to 5 and 29 to 32) and mitomycin-C (10 mg/m(2) on day 2) given with preoperative external beam RT (median 5,040 cGy). Nine patients did not have surgery: 1 refused, 1 died of cholangitis, and 7 were noted to have distant (5) or unresectable local cancer (2) after RT. Of the 25 patients who underwent celiotomy, 11 had liver (8) or peritoneal (3) metastases and 3 had palliative pancreatectomies (2 with liver metastasectomy and 1 with hepatic artery and portal vein replacement). The remaining 11 patients (44% of the cohort with surgery, 32% of all patients) had potentially curative (PC) resections (5 total pancreatectomy 5 Whipple, 1 distal pancreatectomy). Median tumor diameter by computed tomographic scan was 3.75 cm (range 3 to 5) for the 11 patients who received PC resections and 4.5 cm (range 3 to 7.5) for ah patients, Of the 11 patients with PC resections, 8 had evidence of superior mesenteric, portal or splenic venous involvement and 4 had been deemed unresectable at previous celiotomies.RESULTS: One patient developed respiratory failure and one died postoperatively, yielding a 9% rate of major morbidity and mortality. Median follow-up of the surviving patients with curative resection is 33 months (range 14 to 10). Their median survival from the time of tissue diagnosis is 45 months with a median disease-free survival of 27 months. The product limit estimate of 5-year survival is 40% (95% confidence bounds +29%, -30%). One patient had a microscopically positive resection margin, which was a falsely negative frozen section margin at the pancreatic neck. Two patients had positive regional lymph nodes, Five patients have been diagnosed with recurrent cancer. Only 1 has had a local/regional component to the recurrence.CONCLUSIONS: Preoperative RT and chemotherapy followed by resection is well tolerated and safe for patients with locally advanced pancreatic cancer. This approach provides tumor free resection margins and offers prolonged survival to patients with truly localized pancreatic cancer.

Ninety-seven patients with stage IB through IIB cervical cancer metastatic to pelvic lymph nodes treated at Magee-Womens Hospital, Pittsburgh, Pennsylvania, between 1955 and 1979 were analyzed retrospectively to determine histological factors which might predict treatment failure. All patients were treated by radical hysterectomy with a pelvic lymphadenectomy (S) or in combination with radiation therapy (S + RT) (27 and 73%, respectively) and were followed for a minimum of 5 years or until death. There were no significant differences between the two treatment groups when compared for patient age at diagnosis, distribution of disease stages, cell type, and tumor differentiation. The groups were dissimilar only with respect to the number of lymph nodes found to contain metastatic carcinoma. Significantly more patients treated by S + RT than by S alone were found to have metastasis to more than one node. Of patients treated with S alone, 65% recurred within 5 years compared with 51% with the addition of RT (P < 0.16). The extent of both lymphocytic and polymorphonuclear infiltration of the tumor did not influence the probability of recurrence following treatment; however, tumors with a marked eosinophilic infiltration recurred significantly more frequently than those without (P < 0.05).

A malignant meningioma was studied by light and electron microscopy. Histologically, the tumour was composed predominantly of spindle shaped cells arranged in interlacing bundles with numerous mitoses and much nuclear atypia. There were many necrotic foci as well as invasion of the cerebral cortex, dura mater and blood vessels. Ultrastructurally, the main findings included moderate plasma membrane interdigitation, many intracytoplasmic filaments, and junctional attachments of three kinds: desmosomes, hemidesmosomes, and zonulae adhaerentes. These subcellular features are suggestive of arachnoidal cell origin.

Departments of Pathology and Obstetrics and Gynecology University of Pittsburgh Medical School and Magee-Womens Hospital Pittsburgh, Pennsylvania

The histologic and fine structural characteristics of a cystic, papillary, intraluminal benign tumor of the intramural portion of the fallopian tube, incidentally found in a post-menopausal woman, are described here. The tumor is mainly formed by proliferation of mucosal collagenous tissue, covered by typical tubal epithelium; it is called, therefore, a cystic adenofibroma, resembling very closely the histologic appearance of superficial adenofibromas and serous cystadenomas of the ovary and adenofibromas of the cervix which suggest certain consistency in pathologic changes of mullerian structures. This seems to be the first report of this type of neoplasm in the fallopian tube.

Se presentan 15 casos de aspergilosis recolectados en diferentes ciudades del país. Doce fueron casos autopsiados. Los tres restantes se refieren a pacientes en quienes se efectuó una lobectomía pulmonar superior derecha por aspergiloma gigante intracavitario. En los doce primeros existía una enfermedad básica que había alterado seriamente el estado general del paciente; once de ellos habían recibido antibióticos, cinco habían recibido esteroides, y dos, agentes citotóxicos. Se cree que, tanto el estado general del paciente, como la administración de dichas drogas, favorecieron la infección micótica. De los tres casos con aspergiloma intracavitario gigante, se cree que, en uno, la micosis se implantó en una caverna tuberculosa cicatrizada. En los otros dos, la cavidad era un bronquio localmente dilatado y se consideró que no existía una infección tuberculosa.

GONZÁLEZ-ANGULO, AMADOR M.D.; MÁRQUEZ-MONTER, HEÉCTOR M.D.; ZAVALA, BERTHA JUDITH B.S.; YABUR, ELENA B.S.; SALAZAR, HERNANDO M.D. Author Information

Diethylene glycol distearate can be used as an embedding medium for light microscopy. Two infiltration changes of about 6 hr each in the melted wax (melting point 47-52 C) are required before the final embedding which is done in 00 gelatin capsules for sectioning in the ultramicrotome by the procedure used in electron microscopy. Serial sections 1-2 μ thick can be cut without difficulty. No cooling devices are necessary for trimming and sectioning at laboratory temperature. Sections rarely become detached from the slides. The staining characteristics of the tissues are the same as when embedded in paraffin. For fluorescence microscopy, essentially the same procedure is followed. Tissues are not distorted and the intracellular structures are well preserved.

New Zealand virgin rabbits were used in this study. Normal males and castrated, thyroidectomized and recently mated females formed the control groups. Correlation with the light microscopical appearance using the method of alternate thin and thick sections, correlation with the control glands, and comparison with the descriptions in the rat, were used as criteria for the identification of five different types of secretory cells in the pars distalis. Two types of “acidophiles” were found, the more numerous and conspicuous having secretory granules of a maximum diameter of 380–400 mm̈ (growth hormone-producing cell), and a second type with granules of 600–800 mm̈, very seldom seen in the virgin rabbit but increasing in number and granulation after mating (Prolactin-producing cell). Two types of “basophiles” that correspond to the “thyrotrophes” (angular shape, granules of 150 mm̈ in diameter) and “gonadotrophes” (rounded shape, granules of 280–300 mμ), were also identified. In addition, a peculiar large cell with characteristic mottled cytoplasm and very few granules was tentatively identified as a “basophile” in the process of regranulation. Its functional significance was discussed. A stellate cell having fibrillar material and no secretory granules within its cytoplasmic processes, found between parenchymal cells and approaching basement membranes, was tentatively identified as a supporting element. In addition to the description of the fine structure and possible functional significance of the different cell types, some features as cilia, desmosomes, intranuclear fibrillar material, as well as vacuolization of cells in normal glands were also discussed.