Mucosal prolapse syndrome presenting as rectal polyposis.

Mucosal prolapse syndrome comprises a variety of clinical and histopathological entities, with mucosal prolapse as the underlying pathogenic mechanism. Due to variable clinical, endoscopic and histopathological presentation and rareness of symptomatic mucosal prolapse, misdiagnosis resulting in delayed or inappropriate treatment is frequent. This report describes a patient initially diagnosed with a colorectal polyposis syndrome consisting of multiple rectal hyperplastic and adenomatous polyps. But after careful review of medical history and histopathology, the patient was found to have a rare variant of solitary rectal ulcer syndrome presenting as rectal polyposis. The recognition of rectal polyposis as a manifestation of solitary rectal ulcer syndrome/mucosal prolapse syndrome will improve diagnosis and treatment and prevent inappropriate management of this condition.

Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings.

Kayexalate (sodium polystyrene sulfonate) in sorbitol has been demonstrated to cause colonic necrosis in a subset of uremic patients who are administered the cation exchange resin for treatment of hyperkalemia. Upper gastrointestinal damage associated with Kayexalate in sorbitol is reported far less frequently, and the clinicopathologic spectrum of disease in cases with upper gastrointestinal damage has not been investigated previously. The authors studied the clinical, endoscopic, and histologic features of 11 patients with Kayexalate crystals in biopsies from the esophagus (n = 7), stomach (n = 6), and duodenum (n = 2). The endoscopic appearance was markedly abnormal in all 11 patients. The effects of the medication closely mimicked other endoscopic and radiologic diagnoses in three cases, including esophageal carcinoma, Candidal esophagitis, and gastric bezoar. Histologic and/or endoscopic evidence of mucosal injury in the form of an ulcer or erosion was present in nine patients (82%). In four patients with mucosal injury, no other etiology apart from Kayexalate in sorbitol could be identified. In comparison with a cohort of patients with Kayexalate crystals in lower gastrointestinal specimens identified during the same period (11 patients) the frequency of associated mucosal damage was not significantly different (55%, p = 0.19), but no patient with upper gastrointestinal Kayexalate required surgical resection or died as a result of Kayexalate-induced mucosal injury. The results of this study provide evidence that Kayexalate in sorbitol can induce damage to the upper gastrointestinal tract. Recognition of Kayexalate crystals in histologic sections as a marker for sorbitol-induced mucosal damage may aid in establishing the correct diagnosis for clinically or endoscopically misleading lesions.

Papillary urothelial hyperplasia. A precursor to papillary neoplasms.

Precursor lesions of papillary urothelial neoplasms have not been well characterized. We reviewed the surgical pathology files of the Johns Hopkins Hospital and three regional hospitals from 1992 to present. Sixteen cases of papillary hyperplasia, defined as undulating urothelium arranged into thin mucosal papillary folds, were identified (in 11 men and five women: age range, 40-89 years). Relative to the diagnosis of papillary hyperplasia, nine patients had a history of papillary urothelial neoplasms; in one of these cases, the patient also had subsequent papillary urothelial neoplasms, and two of these patients had concurrent papillary urothelial neoplasms with papillary hyperplasia. In one of these nine cases, papillary hyperplasia arose in the scar of a prior papillary urothelial neoplasm. In two cases, the patients had concurrent, yet no prior history, of papillary urothelial neoplasms. Of these 11 cases, three had multiple resections showing papillary hyperplasia over time. In case 12, the patient had a history of moderate urothelial atypia. The remaining four patients had no history of papillary urothelial neoplasms or urothelial atypia. We describe papillary hyperplasia as a well-defined entity that is usually asymptomatic and generally found on routine follow-up cystoscopy for papillary urothelial neoplasms. Papillary hyperplasia appears to be a precursor lesion of low-grade papillary urothelial neoplasms.

Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X; 18).

The authors report an unusual spindle cell sarcoma that arose in the lung of a 12-year-old girl. This tumor had histologic, immunophenotypic, and ultrastructural features consistent with monophasic fibrous synovial sarcoma. These features included a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin immunoreactivity, and focal expression of epithelial membrane antigen and S100 protein. This diagnosis was further supported by cytogenetic studies showing the specific t(X; 18) chromosomal translocation associated with synovial sarcoma. This balanced translocation appears to be an essentially universal characteristic of these sarcomas, regardless of histologic subtype or site of origin. The constellation of morphologic and cytogenetic findings in this case firmly establishes synovial sarcoma as a subtype of pulmonary spindle cell sarcomas. The distinctive features of these neoplasms allow them to be distinguished from a variety of primary and metastatic malignancies in the lung.

Pancreatic polypeptide immunoreactivity in sporadic gastrinoma: relationship to intraabdominal location.

Sporadic gastrinoma is a pancreatic endocrine tumor whose ontogeny is unknown. The anatomic area where the vast majority of sporadic gastrinomas is found (pancreatic head region) corresponds topographically to the area traversed embryologically by the ventral pancreatic bud. Pancreatic polypeptide (PP), a 36-amino acid hormone, is secreted by pancreatic endocrine cells derived almost exclusively from the ventral pancreatic bud and is proposed as a marker for ventral bud derivation. Based on these observations we postulate that sporadic gastrinomas, found around the head of the pancreas, are derived from ventral bud tissue and should display a high incidence of PP immunoreactivity. Overall, we found PP immunoreactivity in 7 of 14 (50%) gastrinomas. Of those tumors located to the right of the superior mesenteric artery (SMA) (around the head of the pancreas), seven of nine (78%) contained PP, whereas no gastrinoma to the left of the SMA (n = 5) contained PP (p = 0.021; Fisher exact test). Only one other pancreatic endocrine or exocrine tumor, a glucagonoma located to the left of the SMA, stained positively for PP. We conclude that sporadic gastrinomas found around the head of the pancreas (to the right of the SMA) have a high incidence of PP immunoreactivity. These findings are consistent with our hypothesis that sporadic gastrinomas are derived from the ventral pancreatic bud.

Intraluminal obstruction of distal ileum caused by a uterine leiomyoma.

A 64-yr-old woman with nausea, vomiting, abdominal pain, and fecal impaction was found at autopsy to have an ileal obstruction by an intraluminal, calcified, spiculated mass. Examination revealed that this calcified mass had the features of a uterine leiomyoma. We postulate that a calcified, pedunculated uterine leiomyoma formed adhesions with the distal ileum, eroded through the ileal wall, and came to rest in the bowel lumen. Here, it was partially digested by the flow of intestinal contents, freed from its pedicle, and ultimately created an ileal obstruction. This rare complication of uterine leiomyomas has not been previously documented.

Human uterine mast cells. Isolation, purification, characterization, ultrastructure, and pharmacology.

As part of an ongoing investigation of human mast cell heterogeneity, we have isolated, partially purified, and characterized the uterine mast cell and compared it with mast cells isolated from other organs. The average histamine content of myometrium and leiomyofibroma obtained from hysterectomies was 2.1 +/- 0.3 (mean +/- SEM) microgram/g of tissue (n = 10), and the histamine content of the two tissues did not differ significantly. A mild collagenase, hyaluronidase, and DNase digestion was used to disperse the uterine mast cells, with an average yield of 9.5% (range, 0 to 21%). The average histamine/uterine mast cell was 2.1 +/- 0.2 pg (n = 3), and 61 +/- 7% (n= 3) of the uterine mast cells survived overnight culture. Early purification efforts with Percoll gradients have yielded up to 80% pure uterine mast cells, with an average of 27 +/- 10% (n = 5). Uterine mast cells released histamine in response to the secretogogues anti-IgE and A23187 but did not respond to substance P or to the basophil secretogogues FMLP, C5a, and 12-O-tetradecanoylphorbol-13-acetate. After 1 microgram/ml anti-IgE stimulation, the uterine mast cell appeared to make significant quantities of PGD2 (89 +/- 26 ng/10(6) cells, n = 6) (p less than 0.05), as assayed by RIA. Simultaneously, leukotriene C4 release was 45 +/- 15 ng/10(6) cells, (n = 6) (p less than 0.05), as assayed by RIA. Combined gas-chromatography mass spectroscopy analysis of anti-IgE-stimulated cell supernatants confirmed the production of PGD2. In pharmacologic studies, isobutyl-methylxanthine and isoproterenol blocked anti-IgE-induced histamine release. The uterine mast cell is similar to the lung mast cell in terms of response to secretogogues and release of arachidonic acid metabolites. Ultrastructurally, the uterine mast cell contains scroll granules, crystal granules, combined granules, homogeneously dense granules, and large lipid bodies, many with focal lucencies within them. Particle granules, most frequently present in gut mast cells of mucosal origin, were absent from uterine mast cells. Although certain features are analogous to the ultrastructure of skin or lung mast cells, the combination of structures is distinctive for uterine mast cells.

Anatomic distribution of pancreatic endocrine tumors.

Pancreatic endocrine tumors are grouped together by their common histologic, cytochemical, and ultrastructural features. Although useful conceptually, this paradigm has been unable to predict the anatomic location of different tumor types. Successful surgical excision of these tumors would be facilitated by an improved understanding of their anatomic distribution. Based on the available data, a bimodal distribution of pancreatic endocrine tumors was identified. Cluster 1 (gastrinomas, pancreatic polypeptide (PP)-secreting tumors, somatostatinomas) had 75% of tumors to the right of the superior mesenteric artery, whereas cluster 2 (insulinoma, glucagonoma) had 75% of tumors to the left of the superior mesenteric artery (p less than 0.05). This distribution is similar to that distribution predicted based on the volume density of the corresponding islet cells for insulinoma, glucagonoma, and PP-secreting tumors, but not for somatostatinoma. These findings suggest that pancreatic endocrine tumors are derived from similar cytologic precursors as pancreatic islet cells, and their distribution may be a consequence of embryologic development from either the ventral (cluster 1) or dorsal (cluster 2) pancreatic buds.

Massive retroperitoneal angiomyolipoma. A lesion that may be confused with well-differentiated liposarcoma.

A benign massive retroperitoneal lipomatous tumor is described. The tumor, from a 72-year-old woman with increasing abdominal girth, consisted of a mixture of mature lipocytes, smooth muscle cells, and thick-walled medium-size blood vessels. Although the tumor focally involved the uterine serosa, suggesting the possible diagnosis of uterine leiomyoma with fatty change, the authors think that, because the bulk of the tumor was located in the retroperitoneum and because the tumor contained characteristic thick-walled blood vessels from which smooth muscle cells radiated, this tumor would be best classified as a retroperitoneal angiomyolipoma. Although both angiomyolipomas and leiomyomas with fatty change presenting as large retroperitoneal tumors are rare, and therefore are not well-recognized by surgical pathologists, they are benign and must be distinguished from liposarcomas.

Mixed müllerian tumors of the uterus: a clinicopathologic study.

Forty-seven cases of mixed müllerian tumors of the uterus were analyzed clinically and pathologically. All patients but one were postmenopausal. Vaginal bleeding was the most frequent presenting symptom, followed by abdominal mass and pelvic pain. Long-term survival was found only in those cases in which the tumor was localized to the uterus (surgical stage I), particularly if it arose from a benign endometrial polyp. No correlation could be established between survival and tumor size, depth of myometrial invasion, or histologic type of sarcoma. Tumors arising after previous irradiation had a poor prognosis. Treatment included surgery, radiation, and chemotherapy. The cumulative probability of 5-year survival was 35%.

Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochemical phenotype.

Three malignant rhabdoid tumors of the kidney and two extrarenal rhabdoid tumors of soft tissues were studied by light and electron microscopy and by immunocytochemistry for the expression of keratin, vimentin, desmin, neurofilament triplet proteins, epithelial membrane antigen, myoglobin, and HNK-1 (Leu-7). Electron microscopy revealed the characteristic cytoplasmic whorled filamentous inclusions in all tumors. An epithelial phenotype (presence of cytoplasmic tonofilaments) was observed in two tumors (one renal and one extrarenal); and a focal primitive neural phenotype (cytoplasmic processes with neurosecretory granules), in a renal rhabdoid tumor. Strands of basal lamina were seen in two renal and one extrarenal rhabdoid tumors. Evaluation of basal lamina was more difficult in the third renal rhabdoid tumor, in which tissue preservation was not optimal. Primitive attachments were present in all rhabdoid tumors. Immunocytochemical staining supported a diverse phenotype, ranging from epithelial and/or mesenchymal to myogenous and/or neuroectodermal. Simultaneous expression of several of the studied antigenic determinants by the same tumor was noted. The findings suggest that both renal and extrarenal rhabdoid tumors express a diverse morphological and immunocytochemical phenotype.

Mixed mesodermal tumors of the ovary: a clinicopathologic study of 14 cases.

Fourteen cases of mixed mesodermal tumor of the ovary are presented. The actuarial survival of patients with these tumors was 2.5 months. Eighty-six percent of patients were stage III or IV at the time of diagnosis. The stromal or carcinomatous component of the tumor could not be correlated with survival. Both our two longest survivors, 14 and 27 months, were treated with surgery and radiotherapy, one patient with and one without chemotherapy.

Ectopic gastrinoma and Zollinger-Ellison syndrome.

In Zollinger-Ellison syndrome (ZES), the discovery of gastrinomas in unusual locations, such as a lymph node, poses a diagnostic problem centered on whether the neoplasm is primary or metastatic. The clinical, gross, microscopic, immunocytochemical, and ultrastructural features of ectopic gastrinomas were studied in four patients with ZES, and reports of 14 similar cases were reviewed. These extragastroenteropancreatic (EGEP) gastrinomas have many of the morphologic features of gastrinomas in conventional locations. However, the centrifugal expansile growth pattern, characterized by a thick fibrous capsule, hyalinized fibrous septa, and, frequently, cystic degenerative changes in EGEP gastrinomas should alert the pathologist to the probability that these neoplasms are primary. Additional evidence for the primary nature of these EGEP gastrinomas is derived from the postoperative normalization of high serum gastrin levels and the correction of the abnormal gastrin response to secretin challenge or to calcium infusion tests. Increased awareness of the occurrence and features of these EGEP gastrinomas is crucial for both pathologists and surgeons to ensure proper evaluation and treatment of patients with ZES.

Blue nevus of the uterine cervix.

The clinical, gross pathologic, and light and electron microscopic features of three blue nevi of the endocervix were studied. Immunocytochemical studies for the localization of S-100 protein in the blue nevus cells were performed. A comprehensive review of 47 previously published cases is also presented. Blue nevi of the endocervix appear to be rare incidental lesions; they are often found in hysterectomy specimens from middle-aged women. The lesion is seldom detected clinically or colposcopically. However, it appears in most instances as a blue-black lesion in the posterior wall of the endocervix on gross pathologic examination. The demonstration of S-100 protein in the blue nevus cells before and after bleaching in the present study, along with the ultrastructural observations, supports combined melanocytic and schwannian differentiation of the blue nevus cell.

Comparison of estrogen-induced hyperplasia to endometrial carcinoma.

Use of exogenous estrogens has been associated with endometrial cancer in a number of case-control studies. This observed association could be biased as a result of frequent misclassification of estrogen-induced hyperplasia as endometrial cancer. To evaluate this possibility, pathology slides from 233 patients with a hospital diagnosis of endometrial cancer were reviewed independently by two pathologists. The hospital diagnosis was confirmed by both pathologists in 86% of the cases, indicating that the misclassification of hyperplasia as carcinoma is uncommon.

Nephrogenic adenoma and embryonic kidney tubules share PNA receptor sites.

Nephrogenic adenoma a rare bladder, ureter, or urethral lesion, is of disputed pathogenesis, metaplastic and congenital etiologies both being implicated in its development. Since light and electron microscopy have been unable to fully resolve the lesion's pathogenesis, the authors used biotinylated lectins as probes and avidin-biotin peroxidase complex (ABC) as a visualant to study cases of nephrogenic adenomas and compared their lectin binding patterns with those of normal transitional epithelium, human embryonic kidneys, and cases of cystitis cystica and glandularis and squamous metaplasia of the bladder in an effort to clarify this issue. Only the epithelial lining of the luminal surface and tubuli in nephrogenic adenoma and tubules in embryonic kidney exhibited free PNA receptor sites. The striking staining similarities between the epithelial components of nephrogenic adenomas and mesonephric and metanephric tubules complement previous findings concerning the origin of nephrogenic adenoma.

Tumor heterogeneity and histopathology in epithelial ovarian cancer.

The histopathology of the original and the persistent or recurrent epithelial ovarian cancer in 34 patients was simultaneously reviewed by two pathologists. The time between removal of the primary tumor and removal of the persistent or recurrent tumor ranged from four to 132 months (median, 13 months; mean, 25 months). The initial operation was followed by multiagent chemotherapy in 23 patients, single-agent chemotherapy in seven, radiation and chemotherapy in two, radiation in one, and no therapy in one patient. In four of the 34 primary tumors, a mixed tumor composition was initially identified. In comparing the initial histopathology with that of persistent or recurrent tumors, a change was identified in nine patients. In four patients, the tumor changed from a mixed to an undifferentiated histologic type; in four patients there was a change from a lower to a higher tumor grade, and two of these patients also had a change in tumor cell type from serous to undifferentiated. In the ninth patient, the tumor changed from a large cell undifferentiated to a small cell undifferentiated carcinoma. The observed changes could be the result of 1) modification of the tumor by cytotoxic therapy, 2) spontaneous dedifferentiation of the initial tumor, 3) tumor cell heterogeneity with preferential growth of one cell type over the others, or 4) the development of a second primary tumor.

Interobserver variability in the interpretation of epithelial ovarian cancer.

The interobserver diagnostic reproducibility for epithelial ovarian neoplasia was studied. The histologic sections of 68 ovarian tumors from 34 patients were independently reviewed by two pathologists from different institutions, without knowledge of the clinical course. Each observer rendered 68 diagnoses. The interobserver agreement rate for histologic type was 60% and for histologic grade 66%. In the 23 instances in which a discrepancy in grade occurred, 5 (23%) were disagreements in the diagnosis of borderline versus malignant tumors. On analysis of the diagnostic variability with regard to histologic type, one observer (A) classified 60% of the tumors as undifferentiated, while the other observer (B) classified 59% of the tumors as serous. In an attempt to understand the reasons for the diagnostic disagreements, the observers were asked to simultaneously reexamine the material. This occurred 6 months after the initial review and they were unaware of their original diagnoses. The diagnostic differences with regard to histologic type were mainly due to (1) tumor cell heterogeneity, and (2) difficulty in discriminating between serous and undifferentiated tumors. The differences in grade were largely related to the use of different criteria. Observer A used mitotic counts while observer B used glandular pattern and its replacement by solid sheets of epithelium. Observer B consistently assigned a higher grade to the tumors. In making therapeutic decisions, clinicians should be aware of the interobserver diagnostic variability and the reasons for this variability.