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Publications and source records attributed to L H Sobin.
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The second edition of Histological Typing of Tumours of the Upper Respiratory Tract and Ear, in the World Health Organization series International Histological Classification of Tumours, provides a comprehensive classification of tumors and tumor-like lesions occurring in (1) the nasal cavity and paranasal sinuses; (2) the nasopharynx; (3) the larynx, hypopharynx, and trachea; (4) the external ear; and (5) the middle and inner ear. The classification includes several newly recognized entities and many that were omitted from the first edition on account of their rarity. The terminology and definitions of several tumor types have been revised in the light of experience gained during the past 12 years. This article discusses the revised classification with special reference to some of the major changes in the listings, terminology, and definitions.
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Twenty-five patients with mucinous tumors of the ovary and appendix were studied. The average age of the patients was 52 years, and the ovarian and appendiceal tumors were discovered synchronously in all but two cases. The majority had either a pelvic mass or abdominal or pelvic pain. A high frequency of bilateral ovarian tumors (11/25), and right-sided predominance for the unilateral ovarian tumors (nine right, five left) were found. Four patients had ovarian mucinous carcinomas, 10 had mucinous tumors of low malignant potential, 10 had mucinous cystadenomas, and one had a mucinous cyst. Pseudomyxoma ovarii was present in 22 cases. Twenty-two of 24 appendices were grossly abnormal. There were six appendiceal mucinous adenocarcinomas, 10 mucinous tumors of uncertain malignant potential, seven mucinous cystadenomas, one hyperplastic polyp, and one mucocele. Twelve patients had ovarian and appendiceal tumors of similar malignant potential, nine had appendiceal tumors with more aggressive morphologic features than the corresponding ovarian tumor, and four had ovarian tumors with more aggressive morphologic features than the appendiceal tumor. Eighteen patients had peritoneal involvement by mucinous epithelium admixed with mucus (nine localized, nine diffuse). Immunoperoxidase reactions for four epithelial antigens in 15 cases showed complete concordance between ovarian and appendiceal lesions in only five cases and were not helpful in determining the site of origin of the peritoneal tumor. Our findings suggest an independent origin of the ovarian and appendiceal tumors in most cases and do not favor an origin in a single site. Furthermore, it is proposed that the peritoneal lesions may arise de novo as part of a multifocal neoplastic process.
Both flow cytometry (FCM) and morphometry have been proposed as techniques for predicting the prognosis of gastrointestinal (GI) smooth muscle tumors (SMTs). In particular, DNA aneuploidy by FCM has been associated with high histologic grade and shortened survival, whereas the DNA index determined by image cytometry has been proposed as a criterion for the diagnosis of malignancy. To further define the potential roles of these two techniques, we performed a variety of morphometric and FCM measurements on paraffin blocks from 122 patients with GI SMTs, with a median follow-up period of 6 years, together with assessments of tumor size and mitotic activity. None of the morphometric measurements (nuclear perimeter, area, form factor, longest diameter, average ferret diameter, equivalent diameter, and DNA index) was a significant prognostic factor when analyzed using a univariate Cox model. In contrast, the flow cytometric mean channel number, the fraction of cells in G2M, aneuploidy of the G0/G1 peak, aneuploidy of the G2M peak, tumor size, and mitotic activity index were statistically significant in univariate models, together with the patient age and sex, and whether or not the patient presented with metastases. In a multivariate model, > 10 mitotic figures per 50 high-power fields and metastases indicated a poor prognosis. If metastasis was not allowed to enter the model, the mitotic index and aneuploidy of the G2M peak portended a poor prognosis.
The second edition of the World Health Organization's Histological Classification of Salivary Gland Tumors is more extensive and detailed than the previous edition published 20 years ago. The new edition is based on data regarding newly described tumor entities and the behavior and prognosis of the previously classified tumors. The distinct morphologic features of monomorphic adenomas justify their separation for purposes of identification. Among the carcinomas, various types were distinguished for purposes of recognition, prognosis, and treatment. The term tumor was replaced by carcinoma in the following two entities: acinic cell carcinoma and mucoepidermoid carcinoma. The tumor-like lesions were described in more detail.
The second edition of the WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts is more comprehensive and detailed than the previous one. Advances in our understanding of dysplasia, carcinoma in situ, various lines of differentiation among the carcinomas, and the recognition of a variety of tumor-like lesions have resulted in more than three times as many entities in the current classification as in the previous one. The new edition should facilitate pathologic, epidemiologic, and therapeutic comparisons.
The Peutz-Jeghers polyp is an unusual type of hamartomatous polyp; its characteristic feature is a smooth muscle core arising from the muscularis mucosae and extending into the polyp. Peutz-Jeghers polyps vary in size and shape; are found in the stomach, small bowel, and colon; and are usually multiple. Peutz-Jeghers syndrome is an inherited condition that often remains undiagnosed until after the polyps are identified, despite mucocutaneous pigmented lesions on the lips and mouth of children or young adults. In the past, standard therapy involved removal of the polyps that produced intussusception, but now endoscopic removal of all polyps is recommended. The polyps are not premalignant, but a definite association exists between Peutz-Jeghers syndrome and gastrointestinal carcinoma. Evidence shows that the syndrome is associated with an increased risk of extraintestinal malignancy, especially carcinomas of the pancreas, breast, and reproductive organs.
Two previous studies have shown higher circulating gastrin levels in subjects with colonic neoplasia than in colonoscopy-negative controls. In this much larger study, sera were collected from fasting subjects undergoing colonoscopy. Colonoscopy with biopsy classified participants as having colonic adenomas (N = 139), colon carcinoma (N = 29), or controls without colonic neoplasia (N = 150). Frozen, stored sera were later analyzed for gastrin by radioimmunoassay. Serum gastrin values were no higher in subjects with colonic adenomas or carcinoma than in colonoscopy-negative controls. We conclude that elevated serum gastrin levels play little, if any, role in the initiation of colonic neoplasia.
The authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine. Most were located in the right colon. Overlying adenomas were present in 45% and squamous differentiation in 21% of tumors. Endocrine differentiation was present in all tumors by at least one method; neuron-specific enolase, dense-core granules, and synaptophysin were present in most cases. Seventy-one percent of tumors metastasized to the liver; 64% of patients were dead at five months follow-up. Twenty-one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine (7 of 21) and squamous differentiation (1 of 15) and fewer liver metastases (4 of 15) than did small cell carcinomas. Among all 59 tumors studied, small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features. Small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement. Although there is a spectrum of squamous, endocrine, and glandular features in large bowel tumors of low degrees of differentiation, the identification of a small cell component appears to be most clinically relevant.
The polypoid manifestations of the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn disease) are often confusing. Inflammatory polyps project above the level of the surrounding mucosa. Pseudopolyposis (in ulcerative colitis) or a cobblestone appearance (in Crohn disease) results when extensive ulceration develops and only scattered islands of relatively normal mucosa remain; thus, the ulcerated areas may be falsely perceived as the baseline and the islands as polyps. Postinflammatory (filiform) polyps--fingerlike projections of submucosa covered by mucosa on all sides--reflect healing of undermined mucosal and submucosal remnants and ulcers and are almost always multiple. Patients with ulcerative colitis or Crohn disease are at increased risk for developing adenocarcinoma. Occasionally, dysplasia occurs as a polypoid lesion. Dysplasia of the colon (mucosal atypia) is a histologic marker highly associated with adenocarcinoma. Because differentiating adenocarcinoma and dysplasia from inflammatory or postinflammatory polyps is sometimes difficult or impossible, endoscopy and biopsy are usually recommended for definitive diagnosis of suspicious lesions.
New techniques in pathology can effect tumor nomenclature by leading to new concepts which may then give rise to new terms. Pathologists generate morphological data. They are obliged to provide consistent data for those who depend on standardized terms, eg, clinical trials, tumor registries and practising physicians and surgeons. They face the dilemma of when to replace a standard term with a new term. The following are recent examples of situations in which new techniques have had an impact on tumor nomenclature but which have raised questions about the applicability of new terms in routine diagnostic reports: --tumors of the lung, particularly when studied by electron microscopy: should the ultrastructural heterogeneity of lung tumor types be expressed or ignored in routine diagnosis? --the APUD and neuroendocrine carcinoma concepts: is there a need to rename carcinoids and small cell carcinomas? --endocrine elements in carcinomas: are the following terms useful for diagnosis: amphicrine carcinoma, argentaffin cell carcinoma, biphenotypic carcinoma? The recognition that conceptual terms and descriptive terms have separate functions may help pathologists deal with terminological change.
Seventy-seven patients with biopsy-proven glandular dysplasia of the esophagus (39 patients) or stomach (38 patients) were followed for a mean of 44 mo or until resection. Of 34 patients with low-grade dysplasia at initial biopsy, 29 had no evidence of high-grade dysplasia or carcinoma on follow-up, three died of other causes, and two had severe dysplasia diagnosed on subsequent biopsy. Of 43 patients with high-grade dysplasia, 28 had no evidence of dysplasia on follow-up (four died of unrelated causes and two of postoperative complications). Fifteen were shown to have invasive carcinoma. Thirteen of the 15 diagnoses of invasive carcinoma were made within 12 mo of original endoscopy. Ulcerated high-grade dysplasias were more likely associated with carcinoma than were nonulcerated high-grade dysplasias (P = 0.001). The presence of ulceration and short time interval to the progression of carcinoma suggest that carcinoma may have been present at the time of initial biopsy in many cases. The frequency of adenocarcinoma's arising in severe dysplasia was slightly less in the stomach (29%) than in the esophagus (41%). We conclude that low-grade dysplasia is often indolent and that ulcerated high-grade dysplasia is often a marker for adjacent invasion.
The World Health Organization's (WHO) histologic classification of gastrointestinal tumors has been revised. Although the general basis of classification and the overall outline remain similar to the first edition, advances in the last decade justified changes in classifying certain entities; among them were malignant lymphomas, endocrine tumors, and dysplasias. Several newly recognized entities have also been added.
Eight patients with von Recklinghausen's disease (VRD) and duodenal carcinoids are presented. Seven patients were black, and one white. Six of the eight were women. The presenting symptom was either jaundice or abdominal pain. All tumors were located in the second portion of the duodenum, and three were multiple. Associated tumors other than neurofibromas included multiple leiomyomas, meningioma, neurofibrosarcoma, and prostatic sarcoma. Seven tumors had psammoma bodies, and in three they were numerous. Somatostatin-positive cells were demonstrated in all cases. Two tumors had spread to regional lymph nodes at the time of surgery. There appears to be a predilection for black patients among those with VRD and duodenal carcinoids.
Eighty-four carcinoids of the colon and rectum were studied with emphasis on prognostic features, immunohistochemical characteristics, and pitfalls in diagnosis. Follow-up data were available on 35 patients. Tumors with adenocarcinomatous components, or those resembling small cell carcinomas of the lung, were excluded. Eighty-one tumors were in the rectum and three tumors were in the distal sigmoid colon. Neuron-specific enolase, chromogranin, and Leu-7 were positive in 87%, 58%, and 53% of the tumors, respectively. Hormones were positive in the following percentages: serotonin, 45%; pancreatic polypeptide, 46%; glucagon, 10%; gastrin, 3%; somatostatin, 3%; adrenocorticotrophic hormone, 1%; cholecystokinin, 0%; calcitonin, 0%; and insulin, 0%. Many tumors elaborated more than one hormone. Fifty-five percent of the tumors were argyrophil and 28% were argentaffin. Carcinoembryonic antigen was present in 24% of the tumors; 82% of the tumors contained prostatic acid phosphatase. Three patients had liver metastases; their tumors ulcerated, invaded muscularis propria, and had more than 2 mitoses per 10 high-power fields (HPF). One patient with a 2.5-cm tumor without mitoses had regional lymph node metastases. All non-metastasizing tumors had less than one mitosis in 10 HPF. We conclude that large bowel carcinoid tumors are essentially limited to the rectum and sigmoid, that they are indolent if mitotically inactive and smaller than 2 cm, and that most show production of a selected group of endocrine markers.
At present, staging of malignant tumors is based on the anatomical extent of disease defined by the T(umor) N(odes) M(etastasis) classification. The main objective of further efforts in classifying tumors is to identify additional independent prognostic factors and to create mathematical models that may predict disease progression by prognostic grouping. This article summarizes problems, methods and the design of coordinated studies on prognostic grouping.
Appendiceal carcinoids with glandular differentiation pose difficulties in classification and prediction of clinical behavior. Sixty-four such cases were divided into three histologic groups on the basis of routine and immunohistochemical stains: (1) Tubular carcinoids were small and confined to the appendix, had small amounts of intraluminal mucin with few or no goblet cells, were nonargentaffin, lacked serotonin, and were diffusely positive for glucagon. All ten with follow-up (mean, 17 months) were without metastasis. (2) Goblet cell carcinoids were confined to the appendix and mesoappendix, circumferentially surrounded the appendiceal lumen, and were often not suspected grossly. Histologically, they were often mixed with small crypt-like glands and were serotonin positive. All 22 with follow-up (mean, 19 months) were without metastasis whether or not right hemicolectomy was performed. (3) Mixed carcinoid-adenocarcinomas showed spread into the cecum or adjacent viscera at the time of diagnosis and had a large carcinomatous pattern with areas of mucinous, signet-ring, or single-file structure, in addition to goblet cell or insular carcinoid. All patients had right hemicolectomies, and all but two with follow-up died of the disease (mean, 16 months). Although a histologic spectrum exists among carcinoid tumors and certain adenocarcinomas of the appendix, it is possible to delineate three biologically distinct groups. Surgical margins should be taken of all appendices because these tumors often do not form discrete masses.