Toshitaka Uehara

MELANOCYTES IN THE NASAL CAVITY and PARANASAL SINUS Incidence and Distribution in Japan

Random, nonselected tissue specimens from 99 Japanese‐20 cylindrically cut nasal blocks removed during autopsy (A.C., Autopsy Cases) and 79 cases removed during surgery, consisting of 32 chronic sinusitis cases (G.S.) and 47 nasal polyp cases (N.P.)‐were examined histopathologlcally and electronmi‐croscopically with respect to distribution and frequency of melanocytes in the nasal cavity and paranasal sinus. Malignant melanoma cases were excluded. The overall incidence of positive cases for melanocytes revealed 21.2% (21 of 99 cases), with an incidence ratio of male to female of 0.9:1.0. Melanocytes were found beginning in the under 19 age group with incidence increasing proportionately with age. Peak incidence was in the 50‐year age group at 50%. Melanocytes and melanotic cell foci were distributed in the stroma of the propria mucosa beneath the pseudostratifled columnar epithelium and focused around the nasal and paranasal glands and sinuses. In 2 of the 21 cases positive for stromal melanocytes, intraepithelial melanocytes with dendritic processes were found. The histogenesis of malignant melanoma arising from the nasal cavity and paranasal sinus are also discussed in this study. ACTA PATHOL. JPN. 37:1105–1114, 1987.

Immunohistochemical characterization of undifferentiated carcinomas of the ovary

Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidinbiotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), α-l-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2,bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining forbcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further celarly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.

Foci of stromal melanocytes (so-called blue naevus) of the uterine cervix in Japanese women.

Foci of stromal melanocytes (FSM) of the uterine cervix have been known as extra-cutaneous “blue naevus”. However macroscopic and histological findings suggest that FSM of the cervix are analogous to dermal melanocytosis, rather than to cutaneous blue naevus and the lesions are more appropriately called stromal melanocytosis. FSM of the cervix have been considered rare, but our study showed that they are not uncommon in Japanese women occurring in 8.6% (42/ 486). The lesions were initially observed in the third decade of life and became most prevalent in the fifth decade (15/86 cases, 17.4%). In stroma of the cervix, stromal melanocytes (SM) were present where many peripheral nerve fibres were seen. SM of the cervix were positive for S-100 protein in immunohistochemical studies and were sometimes observed close to peripheral nerve fibres. Melanocytes were never observed in the ectocervical and endocervical epithelium, but only in the stroma of the cervix. We suggest that malignant melanoma of the uterine cervix may originate from SM.

Stromal Melanocytic Foci (“Blue Nevus”) in Step Sections of the Uterine Cervix

Stromal melanocytic foci (SMF) of the uterine cervix, which are known as extracutaneous blue nevus, were examined in step sections of the cervix. A total of 189 uterine specimens surgically excised for leiomyoma, adenomyosis etc., were studied. The over‐all incidence of SMF of the cervix was 28.6% (54/189 cases). The incidence of these lesions increased with age, and they were most prevalent in the sixth decade of life (12/30 cases, 40%). SMF were presented more often in the anterior wall than in the posterior wall. Most of the lesions were less than 1 mm in size. No case of SMF demonstrated expansive tumorous growth. Six of 54 cases of SMF displayed consecutive spread of SMF in almost all step sections of the cervix. The histological findings confirmed that SMF of the cervix is quite common existence among Japanese women. It is speculated that the mucosal region near the skin and/or cutaneus region near the mucosa may have stromal melanocytosis; malignant melanoma could develop from SMF of the cervix, which did not have junctional activity because of stromal melanocytic origin. Acta Pathol Jpn 41: 751‐756, 1991.

Proliferative and apoptotic status in endometrial adenocarcinoma.

The contribution of cell proliferation and apoptosis to growth patterns in endometrial adenocarcinoma were investigated. Immunohistochemical staining was carried out by an antibody for Ki-67 proliferative antigen, Ley apoptotic antigen, and oncogene products bcl-2 and p53. Forty cases of endometrial adenocarcinoma were classified as exophytic, endophytic, and mixed exo- and endophytic in light of their vertical growth pattern, and, in each case, the carcinomatous area was divided into three layers by its vertical axis. In all but one case, no zonal distribution of the antigen expression was observed. In one case, an exophytic tumor, Ki-67 expression was intense in the surface layer and Ley expression in the deep layer was also intense, suggesting a correlation between macroscopic growth pattern and cellular growth and apoptotic potential. However, in general, zonal distribution of cell proliferation and apoptosis could not explain the growth morphology of endometrial adenocarcinoma of the uterus and it was suggested that factor(s) other than cell proliferation and apoptosis determine macroscopic growth patterns.

Automated Primary Screening Devices

failure might vary widely. During the past year there has been a lull in the previously very active promotion of primary screening devices. It appears that economic projections for the manufacturers did not materialize. This offers a good opportunity to assess the situation and to suggest where the development might go from here. The first question to be raised requires that we return to the beginning. What is the problem that automation of primary screening is to solve? The often-quoted Wall Street Journal article (Bogdanich W: The pap test misses much cervical cancer through lab’s errors. Nov 2, 1987) called attention to several concerns. There were concerns about the reliability of the reading of a Pap smear, about the possibility of shortages in highly trained personnel and about labor costs. The resulting availability of capital for technology development undoubtedly responded to the need to support the control of cervical cancer, but one has to consider that a prime motivation was the potential for economic gain. There is nothing wrong with that notion in principle, but inevitably it had major consequences. The first consequence was that technical solutions to the problem were explored almost entirely with the medical/economic situation in the United States in mind. A device had to process a slide within a very short time frame so that system throughput would meet revenue projections. Device costs were weighed against amortization schemes, projected unit sales and return on investment capital. There were discussions about acceptable false negative rates and how these might be pegged to revised estimates of false negative rates in current laboratory practice. There were serious and justified concerns about the risk of lawsuits in the United States. One cannot help, though, particularly on the ocAfter 35 years of basic research and development, automated screening devices for cervical cancer went into clinical trials and entered clinical practice. The results have been encouraging and might be called a success in several ways. The United States FDA approved two devices; both proved to perform at a level equal to or better than claimed by the manufacturers. Beyond that the field tests established that it should be possible to design systems that might find approval by the cytopathology community. The devices in the clinical trials were, after all, only first-generation designs. There is no complex technology that performs at the level of its potential until several generations of designs have evolved. As first-generation devices, given the very substantial difficulties of the problem and the circumstances under which their development took place, they performed remarkably well. Eliminating design compromises dictated either by the state of technology at the time of development or by the development climate concomitant with venture capital financing would produce the next generation of primary screening systems that come much closer to a performance level well respected by medical professionals. One might hear the argument that since performance of the first-generation devices was critically assessed by the FDA in the United States, why should the profession call for improvements? It is true that the FDA approved these devices. However, one has to understand that the FDA here merely certified that the devices perform at the level claimed by the manufacturer. If one wanted to be unkind, one might suggest that the industry set its own standard. In practice it would essentially be the laboratory director who decides whether a claimed performance level can be maintained and is acceptable or not. The extent to which such a decision would be based on a thorough understanding

Fine needle aspiration cytology of adenocarcinoma of the rectovaginal septum : A case report

BACKGROUND Adenocarcinoma arising in the rectovaginal septum is exceedingly rare and is difficult to diagnose by pathologic examination prior to surgery because of the anatomic position of the tumor. CASE A 42-year-old woman presumed to have adenocarcinoma of the rectovaginal septum underwent fine needle aspiration for diagnosis. Although a previously performed biopsy from the posterior vaginal fornix was unsuccessful, fine needle aspiration cytology via the posterior vaginal wall detected adenocarcinoma cells. The cell clusters were composed of cells with enlarged and hyperchromatic nuclei. The nuclei themselves demonstrated round and/or irregular morphologic patterns, with high nuclear/cytoplasmic ratios, and often contained an enlarged, round nucleolus and sometimes multiple ones in a single nucleus. Aniso-nucleosis was severe, and the chromatin patterns ranged from coarse to finely granular. The cytoplasm was narrow and lightly stained. Following fine needle aspiration, the patient underwent posterior exenteration on the basis of the cytologic diagnosis. CONCLUSION Fine needle aspiration cytology was useful in establishing the preoperative diagnosis of adenocarcinoma of the rectovaginal septum, and curative exenterative surgery could be then performed. To our knowledge, this is the first report of fine needle aspiration cytology of adenocarcinoma at this location.