The microanatomy of vagal body paraganglia (VBP) in the cephalic segment of both vagus nerves was evaluated in an autopsy study of 32 infants one year of age or younger. The study group included 14 victims of sudden infant death syndrome (SIDS) and 18 non-SIDS cases. VBP in both groups were located at or below the lower border of the ganglion nodosum, and were histologically identical to carotid body chemoreceptors, although spatially dispersed and much smaller in size. Using a combined step and serial sectioning technique, there were no significant differences between the two groups (i.e. SIDS vs. non-SIDS) with regard to microanatomy, number, distribution and size of VBP. The proportion of chief and sustentacular cells was similar to carotid body paraganglia. For the study group as a whole, VBP were present in 89% of vagus nerves, and were typically multiple with good correlation between the number of separate paraganglia on the two sides. Small collections of ectopic parathyroid chief cells were identified in 6% of nerve segments, and histologically should be distinguished from VBP. Although the microanatomy of VBP in the SIDS group was identical to that of non-SIDS, one cannot exclude an underlying functional abnormality with autonomic malregulation.

Solitary fibrous tumor (SFT) is a rare neoplasm that, in addition to its classic presentation as a pleural-based mass, can also be encountered in unusual sites. The main difficulty in making the diagnosis of SFTs results from the unfamiliarity with its diverse clinical and pathologic features. This series of SFTs, some with unusual clinicopathologic presentation, included nine women and two men, ranging in age from 28 years to 74 years (five in pleura, one in lung parenchyma, one in breast, and four in mediastinum). The tumors were locally excised in eight cases and were resected along with portions of lung parenchyma in three. A panel of immunohistochemical stains was used to characterize these tumors. They were all vimentin-positive and, with the exception of one case, CD34-positive. Tumors were negative with antibodies directed against cytokeratin, factor VIII-related antigen, S-100 protein, muscle-specific actin, and smooth-muscle actin. Various diagnoses were initially rendered for these clinically and pathologically diverse lesions by the examining pathologists. Awareness of the various gross and microscopic patterns of these tumors, the possibility of occurring in unusual sites, and the use of immunohistochemical stains, particularly CD34, should eliminate most of the difficulties in arriving at a correct diagnosis. One patient died of metastatic breast cancer; all other patients were alive and well with a median follow-up of 17 months.

Fifty-two cases of malignant fibrous histiocytoma (MFH) were evaluated for amplification of the MDM2 gene, mutation of the P53 gene, accumulation of the P53 gene product, and their relation to disease-free and overall survival. All tests were carried out on formalin-fixed, paraffin-embedded tissue samples. Amplification of the MDM2 gene was detected in 15 of 52 cases (29%). Six of 52 cases (12%) demonstrated abnormalities of the P53 gene. Sequence analysis detected point mutations in four cases and a 1-base pair deletion in one case, whereas differential polymerase chain reaction (dPCR) indicated that the P53 gene had been entirely deleted in one case. Eight of 52 cases (15%) demonstrated staining for the P53 protein in >10% of tumor cells. The presence of MDM2 amplification did not have a significant effect on either disease-free or overall survival. Patients with accumulation of the P53 gene product did not differ in disease-free or overall survival from patients without P53 accumulation. Survival also was not significantly different in patients with genetic aberration in P53. However, when the patients were stratified by histologic grade, the results indicated that patients with alterations in the P53 gene may have shorter overall survival.

An apparently novel entity, diffuse hemorrhagic gastroenteropathy (DHG), in a 70-year-old female who had an unremitting course of chronic gastrointestinal blood loss for 3 years requiring transfusion of more than 200 units of packed red blood cells over this period is reported here. Endoscopy showed diffusely hemorrhagic mucosa in the stomach, duodenum, and small bowel. Full-thickness biopsy of the stomach and small intestine revealed luminal narrowing of capillaries and post-capillary venules within the lamina propria due to swelling and some proliferation of the endothelial cells with margination and emigration by neutrophils as well as partial occlusion of some vessels by fibrin thrombi. DHG may represent a new entity characterized by mucosal hemorrhage due to local mucosal ischemia of the gastrointestinal tract secondary to a small vessel "vasculopathy" apparently restricted to this site.

Malignant lymphomas comprise 1-4% of the malignant neoplasms of the gastro-intestinal tract, but appendiceal lymphomas are exceedingly rare. Herein is presented a case of a well differentiated lymphocytic lymphoma of the appendix found incidentally at hernia repair. Forty-six cases of appendiceal lymphoma have been reported since 1898 with a mean patient age of 25.7 years. Thirty-one patients presented with right lower quadrant pain, and a mass was an incidental finding in five. Of the 46 cases, follow-up was possible in 28. There were four deaths within 30 days of the operation and five deaths within 1 year. Although extensive follow-up is limited, there have been only two reported deaths secondary to primary appendiceal lymphoma since 1945 and these two cases are discussed in detail. Based on this extensive review, appropriate recommendations are made.

A sacrococcygeal adenocarcinoma is reported in a male patient nearly 40 years old following resection of a histologically mature sacrococcygeal teratoma. The adenocarcinoma arose within soft tissue of the presacral area and residual coccyx and extensively invaded the coccygeal stump that had not been removed in toto with the teratoma during initial surgery at 2 months of age. The patient died nearly 2 years later with local and regional recurrence of tumor and metastases to lymph nodes, liver, lung, bone, and brain. At autopsy there was no evidence of origin from deep internal organs such as the stomach, pancreas, or other sites. Brief comments are made about malignant tumors complicating sacrococcygeal teratomas in both the pediatric age group and adults, and attention is focused on other lesions entering into the differential diagnosis, particularly retrorectal cyst/hamartoma or tailgut cysts. This case underscores an extremely rare but potentially fatal outcome of a patient with sacrococcygeal teratoma.

Undifferentiated (embryonal) sarcoma of the liver is a primitive mesenchymal neoplasm with predilection for individuals in the first 2 decades of life. In this study (10 boys, 6 girls), children in the age range of 6-10 years were most commonly affected (63%). Clinical features most frequently noted on presentation were abdominal pain or a palpable mass. In two cases there was cardiac involvement caused by invasion of the inferior vena cava with extension into the right atrium and ventricle; both children died of progressive dyspnea from tumor embolization to the lungs. One patient was a member of a kindred with the cancer family syndrome (Li-Fraumeni syndrome). There were 13 tumor-related deaths (86% mortality); one child was alive with recurrent tumor in the upper abdomen. Complete surgical resection was attempted in 10 of 15 children who underwent exploratory laparotomy; 2 were alive and well 1 and 5 years later, whereas 1 patient had a recurrence in the upper abdomen 3 years after diagnosis. Ultrastructural study (five cases) and immunohistochemistry (11 cases) supported a mesenchymal origin for the tumor, but failed to identify any diagnostic immunophenotype or specific line of differentiation. Coexpression of vimentin and cytokeratin was seen in three cases. Prompt detection of this aggressive tumor with complete surgical resection is the key to a successful outcome, but this is very difficult to achieve. Recent experience suggests that aggressive adjuvant chemotherapy may improve survival in some cases.

We report a case of müllerian adenosarcoma of the uterus with benign endometrioid epithelial component and histologically pure angio-sarcoma. This seemingly unique sarcomatous ingredient, among uterine and extrauterine adenosarcomas reported in the English literature, is considered to be a homologous component of the tumor. The patient, a 71-year-old woman with a several-month history of intermittent vaginal bleeding, was found at abdominal hysterectomy to have a large polypoid intrauterine tumor with superficial extension into the myometrium. The patient was treated with 6,000 rad of adjuvant radiation but died a few months after of what clinically appeared to be massive abdominal bleeding. The literature regarding uterine tumors classified as angiosarcoma or malignant hemangioendothelioma is briefly reviewed.

To assess the value of ultrasound (US), fluoroscopy, and spot radiography in the detection, counting, and measurement of gallstone fragments during lithotripsy, in vitro visibility studies were conducted on fragments from 20 stones. Fluoroscopic visibility was evaluated during and after lithotripsy on 185 fragments placed in an anthropomorphic phantom. Three US experiments were performed on the fragments to study the visibility of fragments as a function of size, the accuracy of the count with large numbers of fragments, and the ability of observers to detect and count fragments larger than both 4 mm and 5 mm. With fluoroscopy, fragment detection rates ranged from 20% (fragments larger than 2.5 mm) to 80% (fragments larger than 4.5 mm). With US, all fragments larger than 1.5 mm were detected, and US was significantly better than fluoroscopy and spot radiography for detection of fragments 2.5 mm or smaller. US was also more accurate than fluoroscopy (11% vs 59% error) in the assessment of the number of fragments. When fragments larger than 4 mm or 5 mm were being counted with US, 92% of the fragments were visualized. The results suggest that US is more accurate for monitoring gallstone lithotripsy than fluoroscopy or spot radiography.

In 1983, all trials of omeprazole in humans were stopped because rats given the drug developed gastric endocrine cell hyperplasia and carcinoid tumors. Further studies in rats showed that druginduced achlorhydria and hypergastrinemia caused these changes. Because data in humans are limited, we compared the numbers of endocrine cells, as judged by silver staining (argyrophilia), in the gastric mucosa of patients with Zollinger-Ellison syndrome, who are hypergastrinemic, and in normogastrinemic patients with idiopathic acid-peptic diseases. In addition, we analyzed the number of gastric endocrine cells in patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years. Patients with Zollinger-Ellison syndrome had 15.7% ± 6.9% argyrophil cells in biopsies of gastric oxyntic mucosa, and patients with idiopathic acid-peptic disease had 7.8% ± 2.3% (P < 0.01). In patients with Zollinger-Ellison syndrome, the percentage of argyrophil cells was not related to serum gastrin concentration, duration of symptoms, time since diagnosis, basal or maximal acid output, extent of tumor, or age. There was a tendency for patients with multiple endocrine neoplasia type 1 to have a greater percent of argyrophil cells than patients with sporadic Zollinger-Ellison syndrome. Considering the biopsies from both normogastrinemic and hypergastrinemic patients, there was a significant relationship between the percentage of argyrophil cells and the serum concentration of gastrin (P < 0.01). Patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years developed no significant changes in percentage of argyrophil cells, no carcinoid tumors, and no changes in serum concentrations of gastrin. The present study shows that patients with Zollinger-Ellison syndrome have an increased percentage of argyrophil cells in oxyntic mucosa and that omeprazole does not increase this percentage. In periods of up to 3 years, omeprazole had no effects on gastric morphology in patients with Zollinger-Ellison syndrome.

From July 1975 to February 1985, 300 patients with extremity soft tissue sarcomas (STS) were entered into treatment protocols at the National Cancer Institute. Using the Cox proportional hazards model, the STS were analyzed for independent prognostic variables that had significant association with disease-free and overall survival. The effects of adjuvant treatment were also included in the analysis. Percent tumor necrosis was the basis for separating intermediate and high-grade STS (less than 15% necrosis = grade 2; greater than 15% necrosis = grade 3). The most important prognostic variable was histologic grade, which was highly associated with relative risk of metastasis and fatal outcome (P less than .0001). Histologic type of STS was not a significant prognostic variable in predicting metastases. Patients with tumors located on the proximal or middle part of the extremity had a fivefold increased risk of death (P = .02) compared with patients who had STS located more distally. Mitotic activity (P = .0005) and vascular invasion (P = .0034) were also associated with malignant behavior, but histologic grade was the most significant predictor of outcome. Histologic grade of malignancy was based upon a combination of tumor typing and visual estimation of extent of tumor necrosis; using these two features, one can reliably separate low-grade (i.e., grade 1) from high-grade STS and also stratify the more aggressive (i.e., grade 2 and 3) tumors. Over the 9.5-year period of study, the tumor-related mortality was as follows: grade 1 (1/38), 3%; grade 2 (19/142), 13%; and grade 3 (45/120), 38%.

Histologic classification and subtyping of primary tumors of the exocrine pancreas have great prognostic value, although most tumors--such as duct cell adenocarcinomas--are consistently high grade with respect to biologic behavior. The mortality rate for these tumors is nearly equal to the incidence rate, and prognosis does not appear to be significantly influenced by histologic grade of the primary tumor. Other tumors, such as solid and papillary epithelial neoplasms, have intermediate to low malignant potential, while microcystic adenomas have proved to be essentially benign. Recent application of immunohistochemistry, along with electron microscopy, has helped to elucidate the histogenesis of some tumor subtypes. An intestinal phenotype has been demonstrated for mucinous cystic neoplasms with goblet cells, Paneth cells, and a variety of endocrine cells. Divergent tumor differentiation has been seen in a rare group of mixed tumors with variable composition of duct, acinar, or endocrine cells. Some infantile pancreatic tumors, known as pancreatoblastomas, may also show mixed-cell composition. Immunohistologic studies of solid and papillary epithelial neoplasms have not yet identified a consistent or reliable phenotype or marker, and ultrastructural studies have reached disparate conclusions regarding histogenesis. The rarity of other tumors--e.g., those with osteoclasttype giant cells--has hampered complete characterization.

We have examined 11 patients with the acquired immunodeficiency syndrome (AIDS) for evidence of subclinical vitamin B12 malabsorption. Three subjects (27%) had low levels of vitamin B12. Eight subjects (73%), including these 3 subjects plus 5 others with normal vitamin B12 levels, had abnormal Schilling test results. In addition, 15% of an unselected population of 121 patients with AIDS and 7% of 27 patients without AIDS who were seropositive for human immunodeficiency virus type 1 (HIV-1) had low serum vitamin B12 levels. Stool cultures from the 8 subjects with abnormal Schilling test results revealed no pathogens. Intestinal involvement by Kaposi's sarcoma was found in only 1 patient. Biopsy specimens from 5 of 6 patients with vitamin B12 malabsorption, however, contained mononuclear cells harboring HIV-1, as indicated by in situ hybridization studies. Our observations suggest that vitamin B12 malabsorption is common in patients with AIDS and may be a very early manifestation of infection with HIV-1.

Pulmonary artery sarcomas are a rare and frequently forgotten cause of pulmonary artery occlusion. We present a case report that details magnetic resonance and new CT findings, which may help establish early diagnosis of this infrequently encountered tumor.

During a 4.4-year period, nonspecific interstitial pneumonitis was seen in 41 of 110 (38%) patients with the acquired immunodeficiency syndrome and accounted for 32% (48/152) of all episodes of clinical pneumonitis. Diffuse alveolar damage was typically a feature of nonspecific interstitial pneumonitis, but neither lung biopsy nor bronchoalveolar lavage detected a pathogen. Of these 41 patients, 13 had no associated pulmonary tumor and had not been exposed to pulmonary toxins, whereas 28 patients had either concurrent pulmonary Kaposi sarcoma, previous experimental therapies, or a history of pneumocystis pneumonia or drug abuse. Of these 41, 23 had normal chest radiographs. The clinical features of patients with nonspecific interstitial pneumonitis were similar to those of patients with pneumocystis pneumonia, although histologic findings showed less severe alveolar damage in patients with nonspecific interstitial pneumonitis (p less than 0.001). Pathologic evaluation and clinical follow-up suggest that many clinical episodes of pneumonitis in patients with the acquired immunodeficiency syndrome are due to nonspecific interstitial pneumonitis of unknown cause.

Brenner, Matthew; Ognibene, Frederick P.; Carrasquillo, Jorge A.; Lack, Emest E.; Suffredini, Anthony F.; Parrillo, Joseph E.; Lane, H. Clifford; Fauci, Anthony S.; Masur, Henry; Shelhamer, James H. Author Information

Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis of this evidence, this lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with the acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment with the reduced folate leucovorin was used as a specific antidote to protect host tissues from the toxic effects of the antifolate without affecting the antipneumocystis action of trimetrexate. Patients were assigned to three groups and treated for 21 days: in Group I, trimetrexate with leucovorin was used as salvage therapy in patients in whom standard treatments (both pentamidine isethionate and trimethoprim-sulfamethoxazole) could not be tolerated or had failed (16 patients); in Group II, trimetrexate with leucovorin was used as initial therapy in patients with a history of sulfonamide inefficacy or intolerance (16 patients); and in Group III, trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (17 patients). The response and survival rates were, respectively, 69 percent and 69 percent in Group I; 63 percent and 88 percent in Group II; and 71 percent and 77 percent in Group III. Trimetrexate therapy had minimal toxicity; transient neutropenia or thrombocytopenia occurred in 12 patients and mild elevation of serum aminotransferases in 4. We conclude that the combination of trimetrexate and leucovorin is safe and effective for the initial treatment of pneumocystis pneumonia in patients with AIDS and for the treatment of patients with intolerance or lack of response to standard therapies.

A review of all primary hepatic tumors seen at Children's Hospital, Boston over a 57-year period disclosed six cases of focal nodular hyperplasia (FNH) and two hepatic adenomas (HA). The children with FNH (four females, two males) ranged in age from 6 months to 15 years (average age: 7 years). Three patients had "hepatomegaly" noted on physical examination 2 months to 2 or more years prior to diagnosis. The average diameter of FNH was 7.3 cm (range 2.5-10 cm). The lesion was confined to the right lobe in four cases and showed bilobar involvement in two. The HA's were diagnosed in a newborn male and a 2-year-old girl, both of whom were symptomatic because of large tumor size (10 cm each). There was no maternal history of exposure to exogenous steroids during pregnancy. Three children with FNH underwent hepatic lobectomy and were alive and well 4 to 17 years later. One child who died of acute leukemia had an incidental FNH discovered at autopsy. Two patients were treated conservatively with biopsy only and were alive and symptom-free 13 and 15 years later. Both children with HA underwent hepatic lobectomy. One died postoperatively because of intra-abdominal hemorrhage and the other was alive and well 10 1/2 years later. Complete surgical resection is recommended for most children with HA when technically feasible because of the lingering suspicion of possible (albeit remote) malignant transformation and diagnostic difficulties in distinguishing HA from a well-differentiated hepatocellular carcinoma.

From 1975 through 1983, 69 patients with hereditary angioneurotic edema were treated with danazol, a semisynthetic anabolic steroid. Hematuria developed in 13 of these patients (19 per cent). Careful evaluation of the genitourinary tract showed the presence of a distinct form of hemorrhagic cystitis in 10 patients. Clinically, 9 patients presented with microscopic and 1 with intermittent gross hematuria. Irritative bladder symptoms were reported by 2 patients. Neither the dose nor duration of danazol therapy correlated with the severity of the cystoscopic or pathological findings. Cystoscopically, a rather nonspecific pattern of erythema, submucosal telangiectasia and neovascularity was observed. Histopathologically, bladder biopsy typically showed numerous dilated submucosal vessels with hemorrhage, mucosal ulceration and occasional inflammatory cells. These changes regressed in all but 1 patient when danazol therapy was discontinued. Further studies are needed to elucidate the role of danazol itself or of the danazol-hereditary angioneurotic edema interaction in the pathogenesis of these abnormalities.

Mesenchymal hamartoma (MH) is a rare but distinctive tumor-like malformation of the liver with predilection for infants in the first 2 years of life. MH accounted for only 5% of all primary hepatic tumors seen at Children's Hospital, Boston, over a 57-year-period from 1924 through 1981. There were nine children (five females, four males) with a median age of 11 months at the time of diagnosis (range: 5 months to 7 years). The most common presenting manifestation was abdominal enlargement with a palpable nontender mass. Exploratory laparotomy was performed in each case. The MHs were located in the right lobe and varied in size from 3 to 21 cm (average diameter, 16 cm). One MH also involved a portion of the left lobe. Four of seven children who underwent hepatic lobectomy were alive and symptom-free for 1 to 18 years later. There were three intraoperative deaths due to hemorrhage and cardiac arrest. One child underwent biopsy only with drainage of cyst fluid but died in the postoperative period because of pneumonia. The last child who had wedge resection of an incidental MH died of extrahepatic biliary atresia. Although complete surgical resection is curative, past experience indicates a substantial risk for operative mortality. In some cases, a more conservative approach to therapy is suggested with partial excision or drainage of cysts and possible resection at a future date.