Peripheral pulmonary papillary adenocarcinoma with prominent cilia: report of a rare case that was difficult to diagnose preoperatively.

BACKGROUND: In pulmonary cytology, the existence of cilia is considered cytologic evidence of benign cells because it is generally considered that cilia could not be identified by light microscopic observation of pulmonary adenocarcinoma. However, we encountered a rare exceptional case of pulmonary adenocarcinoma with cilia. CASE: A 55-year-old woman with bloody sputum was admitted. Computed tomography revealed a lung tumor. Although transbronchial brushing cytology showed atypical cells suggestive of malignancy, some atypical cells had cilia, so we could not diagnose them as cancer cells. After antibiotic therapy, the tumor was surgically excised. Imprint cytology showed similar atypical ciliated cells. Histologically, the tumor was diagnosed as papillary adenocarcinoma with cilia and diffuse pleural dissemination was observed. Electron microscopic observation identified cilia. The patient died due to aggravation of cancer, which was confirmed on autopsy. CONCLUSION: This rare case of peripheral pulmonary papillary adenocarcinoma with cilia could not be diagnosed as cancer cell on cytology. Pulmonary papillary adenocarcinoma with cilia should be considered in the differential diagnosis of atypical cells in pulmonary cytology.

Malignant myoepithelial cells are associated with the differentiated papillary structure and metastatic ability of a syngeneic murine mammary adenocarcinoma model.

BACKGROUND: The normal duct and lobular system of the mammary gland is lined with luminal and myoepithelial cell types. Although evidence suggests that myoepithelial cells might suppress tumor growth, invasion and angiogenesis, their role remains a major enigma in breast cancer biology and few models are currently available for exploring their influence. Several years ago a spontaneous transplantable mammary adenocarcinoma (M38) arose in our BALB/c colony; it contains a malignant myoepithelial cell component and is able to metastasize to draining lymph nodes and lung. METHODS: To characterize this tumor further, primary M38 cultures were established. The low-passage LM38-LP subline contained two main cell components up to the 30th subculture, whereas the higher passage LM38-HP subline was mainly composed of small spindle-shaped cells. In addition, a large spindle cell clone (LM38-D2) was established by dilutional cloning of the low-passage MM38-LP cells. These cell lines were studied by immunocytochemistry, electron microscopy and ploidy, and syngeneic mice were inoculated subcutaneously and intravenously with the different cell lines, either singly or combined to establish their tumorigenic and metastatic capacity. RESULTS: The two subpopulations of LM38-LP cultures were characterized as luminal and myoepithelium-like cells, whereas LM38-HP was mainly composed of small, spindle-shaped epithelial cells and LM38-D2 contained only large myoepithelial cells. All of them were tumorigenic when inoculated into syngeneic mice, but only LM38-LP cultures containing both conserved luminal and myoepithelial malignant cells developed aggressive papillary adenocarcinomas that spread to lung and regional lymph nodes. CONCLUSION: The differentiated histopathology and metastatic ability of the spontaneous transplantable M38 murine mammary tumor is associated with the presence and/or interaction of both luminal and myoepithelial tumor cell types.

Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium.

To determine whether pulmonary alveolar capillaries manifest ultrastructural remodeling at areas of neoplastic invasion of primary lung adenocarcinomas, we examined 17 well-differentiated adenocarcinomas of lung (2 bronchioloalveolar and 15 papillary adenocarcinomas) by electron microscopy. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was demonstrated by immunohistochemical stainings. VEGF messenger RNA (mRNA) isoforms were detected by reverse-transcription polymerase chain reaction (RT-PCR) in alveolar walls microdissected from normal and tumor-associated tissues. Cytoplasm of neoplastic cells expressed VEGF protein in all patients. Endothelial cell nuclei of alveolar capillaries showed positive reaction for PCNA. Alveolar capillary lumina were distended like venules, and some intercellular junctions remained open. The cytoplasm of the capillary endothelial cells was enlarged and developed numerous organelles such as Weibel-Palade bodies and vesiculovacuolar organelles, in contrast to marked attenuation in their normal counterpart. Capillary sprouting occurred from proper alveolar capillaries in 2 patients. Cytoplasmic segments became extremely attenuated and developed diaphragm-like fenestrae in 65% of the patients. A relatively higher expression of diffusable isoforms of VEGF mRNA was seen in the tumor-bearing alveolar walls than in normal walls. Expression of KDR (one of the VEGF receptors) mRNA in tumor exceeded that in normal tissues. These results suggest that diffusable isoforms of VEGF mRNA released from the neoplastic cells are deeply involved in the induction of growth activity of alveolar capillary endothelial cells as much as in the characterization of tumor-associated microvessels in primary lung adenocarcinomas.

Nuclear grooves. How specific are they?

OBJECTIVE: To study the significance of nuclear grooves in thyroid and extrathyroid benign and malignant lesions. STUDY DESIGN: In this retrospective study, 26 cases were selected randomly, consisting of papillary carcinoma of the thyroid (7), papillary adenocarcinoma (9), normal cervical smear (5) and benign bronchioalveolar lavage (BAL) (5). In all cases hematoxylin and eosin- and Papanicolaou-stained smears were studied for nuclear grooves. RESULTS: Except for one case of papillary adenocarcinoma, nuclear grooves were discernible in all cases. The highest number of nuclear grooves was seen in normal cervical smears, followed by papillary carcinoma of the thyroid, papillary adenocarcinoma and BAL smears. CONCLUSION: The number of grooves did not correlate with either benign or malignant conditions. These findings cast serious doubt about the diagnostic significance of nuclear grooves. Probably nuclear grooves are nonspecific findings and should be considered only in association with other diagnostic features.

Ultrastructural study of intranuclear inclusion bodies of pulmonary adenocarcinoma.

Intranuclear inclusion bodies are sometimes observed in pulmonary adenocarcinoma by light microscopy. Electron microscopic characteristics of lung cancer cells with intranuclear inclusion bodies were studied. In addition, polymerase chain reaction (PCR) was performed using primers coding for human papillomavirus (HPV) types 16, 18, and 33. Eosinophilic intranuclear inclusion bodies were observed in 22 out of 285 cases by light microscopy. Immunohistochemically, cancer cell nuclei stained with PE-10. Three types of intranuclear inclusion bodies were classified electron microscopically. Type A showed aggregation of electron dense particles (30-40 nm) with an electron-dense core and was most frequently observed. Type B consisted of a mass of branching and whirling tubular structures. Type B intranuclear inclusions had a relationship with inner nuclear membrane. In type C, several spherical inclusions were observed in one nucleus. HPV DNA was detected using PCR and type-specific probes in a case with type A inclusion bodies. This study suggests that intranuclear inclusion bodies in pulmonary adenocarcinoma are formed by several different mechanisms.

Scanning electron microscopic study of the three-dimensional structure of the collagen networks of gastric cancer.

The three-dimensional structure of the collagen networks in human gastric carcinoma was examined by scanning electron microscopy (SEM) after treatment with the cell-maceration method using a low temperature NaOH solution. Based on stromal content, the poorly differentiated adenocarcinoma can be divided into the medullary carcinoma area and the scirrhous carcinoma area. In the medullary carcinoma, the collagen sheath around the small tumor cell acinus formed spherical chambers (20-30 microns in diameter) with fenestrations (about 5 microns in diameter) connecting the chambers. The collagen sheath was composed of fine collagen fibrils (about 50 nm in diameter). In the scirrhous area, there was abundant fibrous stroma composed of thicker collagen fibrils (about 100 nm in diameter). Tiny tumor cell nests were sporadically seen in the fibrous stroma. These tumor nests were surrounded by collagen fibrils (about 50 nm in diameter). In the moderately differentiated tubular adenocarcinoma, the tumors were surrounded by spherical, ovoid or irregular shaped thick collagen sheaths (50-200 microns in diameter), which were composed of loosely packed 50 nm collagen fibrils. In well differentiated tubular adenocarcinoma, tumor glands were surrounded by spherical, ovoid or irregularly-shaped thick collagen sheaths (50-200 microns in diameter), composed of densely arranged fine collagen fibrils. In papillary carcinoma, the collagen sheaths were nipple-shaped. They were composed of very densely arranged fine collagen fibrils (about 50 nm in diameter).

Primary papillary psammomatous adenocarcinoma of the umbilicus.

The histological and ultrastructural features, as well as the immunoreactivity of one case of uncommon primary papillary and psammomatous adenocarcinoma of the umbilicus are studied in the present work. The observations have been undertaken in a nine-year follow-up, and have included the primitive tumour, two local recidives, and inguinal lymphatic metastasis on two occasions. Papillary structures, numerous psammoma bodies, as well as weak and focal positive reactions to CEA and cytokeratin were present in all the tumours. Since these features and their ultrastructural characteristics were identical to primary papillary serous neoplasias of the peritoneum and ovarium, the hypothesis of an origin in coelomic remnants is considered.

Basement membrane components in mammary tumours of the dog and cat.

The distribution of the basement membrane (BM) components, laminin, type IV collagen and type VII collagen were studied immunohistochemically in benign and malignant growths of the mammary epithelium of the dog and cat. Intact BMs were found in benign growths, but in well-differentiated malignant tumours they were generally discontinuous, and missing in poorly differentiated carcinomas. An increase in the histological grade of atypia was accompanied by a more marked disruption or fading of BM. Monoclonal antibody (LH 7.2) proved useful in demonstrating type VII collagen in tumours in which massive proliferation of blood vessels made the evaluation of BM features with antibodies to laminin and type IV collagen difficult. Type VII collagen is present in BM of the mammary epithelium but not under the endothelium of blood vessels; it may therefore enhance the value of BM markers as aids in the study of neoplastic progression.

Papillary adenocarcinoma of the epididymis.

An 82 year old man with a unilateral epididymal mass was found, on histopathologic examination of a surgically removed specimen, to have a primary papillary adenocarcinoma of a clear cell variant which mimicked renal cell carcinoma. Repeated imaging studies confirmed the absence of renal cell carcinoma. Because the present case had great similarities in histologic appearance and anatomical location to papillary cystadenoma of the epididymis, it may be a malignant counterpart of the latter type of tumor.

High incidence of nuclear accumulation of p53 protein in gastric cancer.

The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.

Ciliated cells in papillary adenocarcinomas of Barrett's esophagus.

Eighteen surgical specimens having an adenocarcinoma arising in Barrett's esophagus were reviewed, and special attention was paid to the presence of ciliated cells. The tumors were classified as glandular (9), papillary (4), diffuse (3) and mixed (2) types. Ciliated cells were observed in one specimen, in cystically dilated glands in Barrett's mucosa adjacent to a papillary adenocarcinoma. Ciliated tumor cells were found in three of the four papillary adenocarcinomas. The fourth papillary tumor, 1 mixed papillary-diffuse adenocarcinoma and the remaining 13 adenocarcinomas had no ciliated cells. Thus, the presence of cilia in exfoliated tumor cells from the esophagus should raise the suspicion of a papillary adenocarcinoma arising in Barrett's mucosa.

DNA ploidy in gastric cancer with metastasis to the liver.

DNA ploidy, assessed microspectrophotometrically in 143 gastric carcinomas, was correlated with the presence or absence of venous invasion and liver metastasis. Patterns of DNA distribution were grouped into cases of low and high ploidy. The incidence of high ploidy was 61.4% in gastric cancers with venous invasion, being statistically different from the incidence of 31.4% in cases without venous invasion (P less than 0.05). Furthermore, there was a statistical difference between the incidence of high ploidy in gastric cancers associated with liver metastasis and the incidence of high ploidy in advanced cancers that had been curatively resected and had not recurred for more than 5 years after operation (P less than 0.05). These findings indicate a close correlation between DNA ploidy, venous invasion, and liver metastasis, and they suggest the significant clinical value of DNA analysis for the prediction of liver metastasis in patients with gastric carcinoma.

A case report of papillary adenocarcinoma in sublingual region--ultrastructural and histochemical study.

A rare case of papillary adenocarcinoma located in the sublingual region is presented. This case was initially considered to be a hemangioma and then the tentative clinical diagnosis was thyroglossal duct cyst at the time of the operation under general anesthesia. However, the final histopathologic diagnosis was papillary adenocarcinoma. We investigated its origin by histological, ultrastructural and histochemical techniques and it was suggested that this tumor arose from the minor salivary gland.

Ultrastructural morphometric analysis of papillary neoplasms: biological and diagnostic relevance.

Ten papillary adenocarcinomas of thyroid origin (P-Thy), ten papillary adenocarcinomas of ovarian origin (P-Ov), and eight papillary neoplasms of non-thyroid/non-ovarian origin (P-Other) were morphometrically compared using 19 distinct quantitative nuclear and nucleolar parameters as a database for diagnosis. The selected cases consisted of 16 primary and 12 metastatic neoplasms. It was determined that the P-Thy group had a significantly smaller nucleolar area (NuA) and nucleolar perimeter (NuP), and smaller SDs of nuclear area (NA), NuA, and NuP compared with the P-Ov and P-Other groups (P less than .05). The P-Ov group had a significantly smaller SD of NA compared with the P-Other group (P less than .05). The P-Ov group exhibited the greatest variability among the papillary neoplasms. Linear regression analysis indicated that in the P-Thy group alone there was a significant correlation between mean nuclear form factor (4 pi A/P2) and mean NuA (r = -.82; P less than .01), and mean NP and mean NuA (r = +.77; P less than .01). Linear regression analysis also indicated that in the P-Ov group alone, there was a significant correlation between mean NA and mean NuA (r = +.75; P less than .02). Morphometric domains were established using statistically significant sets of variables that distinguished between the groups. The application of three-dimensional computerized cluster analysis techniques indicated that the P-Thy group consistently had the smallest morphometric domains. It was concluded that ultrastructural morphometric analysis of papillary neoplasms has diagnostic potential and reveals interesting biological relationships among distinct nuclear features in the different groups of neoplasms.

Multicentric papillary adenocarcinoma of the renal pelvis and ureter. Report of a case with ultrastructural study.

A case of multicentric papillary adenocarcinoma arising in the renal pelvis and proximal ureteral mucosa of a 35-year-old man is presented. The left nephrectomy specimen demonstrated multiple, fungating, papillary tumors. The largest tumor measured 10 X 9 X 6 cm and invaded the renal parenchyma. Smaller tumors with long stalks were found. Microscopically, the papillary fronds of each neoplasm were lined by a single layer of cuboidal to low columnar epithelium admixed with a few areas of invasive tubular adenocarcinoma. The adjacent pelvic mucosa was the site of cuboidal epithelial metaplasia. The ultrastructure of both the papillary tumor and the pelvic mucosa suggested that they originated from the nonmucigenic metaplastic epithelium with a partial similarity to the lining of the proximal convoluted tubule. The growth pattern and the multicentric development of this unusual neoplasm suggest that this is a case of the malignant counterpart of the nephrogenic adenoma in the kidney and ureter, and reflect a biologic behavior corresponding to ordinary urothelial papillary tumors.

Papillary adenocarcinoma of rete testis. Autopsy findings, histochemistry, immunohistochemistry, ultrastructure, and clinical correlations.

Adenocarcinoma of the rete testis is a rare neoplasm that usually occurs in men after the age of 60 and carries a variable prognosis. We report an occurrence of this tumor in a 91-year-old man who had been treated for 2 years for an hydrocele. At the time of diagnosis, metastases were not evident; and the patient was treated with local radiotherapy. The diagnosis of papillary adenocarcinoma of the rete testis was made on the basis of: (a) a transition from normal rete testis to atypical and neoplastic rete epithelium; (b) exclusion of primary germinal and nongerminal testicular tumors and spread from distant sources; and (c) electron-microscopic findings, histochemical and immunological studies, and autopsy findings supporting the diagnosis. This is the first reported case of adenocarcinoma of the rete testis that includes documentation of the tumor's metastatic pattern.

Mucus-producing adenopapillary carcinoma of minor salivary gland origin with signet ring cells and intracytoplasmic lumina. A light and electron microscopic study.

A histological and subcellular study of a mucus-producing adenopapillary carcinoma of a minor salivary gland is presented. The tumor was located on the buccal mucosa of a 36-year-old white man. Microscopic examination showed that the tumor was an invasive papillary growth with numerous signet-ring cells and mucous production. When viewed under the electron microscope, the tumor exhibited clusters of cells showing intracellular lumina and finely dispersed chromatin.

Morphological and biological characteristics of mammary tumours induced by the direct application of DMBA powder to rat mammary glands.

Mammary tumours were induced by the direct dusting of 1 mg, 7,12-dimethylbenz(a)anthracene (DMBA) powder onto the mammary gland of both 30-day-old female and male Sprague-Dawley rats, and the tumours were examined histologically. Mammary tumours developed in 43/43 (100%) of the females 11 to 20 weeks after DMBA dusting and 16/23 (70%) of the males 18 to 28 weeks after dusting, while non-mammary spindle cell sarcomas occurred in 5/23 (22%) of the males 15 to 24 weeks after dusting. A variety of benign and malignant mammary tumours of epithelial and/or mesenchymal origin were induced, which are comparable to human mammary tumours. Different histological patterns were observed in different areas of the same tumours. Ovariectomy revealed hormone (ovary)-dependency in 10/17 (59%) of the tumours, revealing regressing epithelial and proliferating mesenchymal tumour elements on histological examination.