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This report is on a 33-year-old female patient with Crohn's disease of the intestine and nonhealing leg ulcers which histologically showed the typical noncaseating epithelioid granulomas of sarcoid structure defining the so-called 'metastatic Crohn's disease'. Furthermore, as a very rare pattern, extensive necrobiotic areas surrounded by sarcoid granulomas were observed.
We evaluated the cellular distribution of calcitonin (CT), L-dopa decarboxylase (DDC), and histaminase [diamine oxidase (DAO)] in 33 patients with medullary thyroid carcinoma (MTC). CT immunostaining was uniform (greater than 90% of the cells) and intense (4+) in lesions from 7 patients with C-cell hyperplasia and 6 with microscopic MTC: conversely, patchy CT staining (less than 40% of the cells) and diminished intensity (1+) were found in metastases from 8 patients who died of virulent disease. In 17 patients who underwent thyroidectomy for macroscopic cervical MTC with no evidence distant metastases, CT staining was intense (3-4+) and homogeneous (greater than 90%) in 11 subjects who were well 0.5-16 yr postoperatively. Six patients with similar clinical presentations had heterogeneous staining for CT in primary tumor (less than 40% of the cells; 1-2+ intensity); 5 died of disseminated MTC 0.5-5 yr postoperatively (P less than 0.001). Biochemical studies of distant metastases revealed an inverse relationship between the distribution of CT and that of both relationship between the distribution of CT and that of both DDC (r = 0.71; P less than 0.01) and DAO (r = 0.81; P less than 0.001). We conclude that cellular heterogeneity in MTC tissue is associated with a distinct biochemical pattern, and its presence, whether in a primary or metastatic lesion, indicates a virulent neoplasm associated with a grave prognosis.
Cell lines which exhibit epithelial morphology with surface microvilli and inclusion bodies characteristic of type 2 pneumocytes have been derived from normal adult mouse lung by a simple procedure involving enzymatic dispersal and mechanical elimination of other cell types. One of these cell lines designated NAL 1A, examined in detail, shows features consistent with its being related to type 2 pneumocytes of mouse lung. These features include desmosomes, dense lamellar bodies as well as phospholipid profiles related to immature surface active material, the inhibition of cell growth rate by dexamethasone, and the close similarity of the cytoskeletal protein patterns of this cell line to those of a metastatic type 2 pneumocyte-related cell line of mouse lung. The cell line from normal lung demonstrated near diploid chromosome number at low passage number with some evidence of karyotype instability at high passage number.
The supplementary motor area (SMA) is a region located within each cerebral hemisphere at the posterior mesial border of the frontal lobe adjacent to the falx. The functional significance of this area has been somewhat unclear, and information regarding its influence on motor output has largely been based on evoked responses to direct stimulation in primates and humans. In this series of patients with primary and metastatic tumors involving the dominant hemisphere SMA, a distinct pattern of postoperative deficits and recovery has emerged which emphasizes the role of this critical area in the initiation of motor activity, including speech. Based upon this analysis, ablation of this region after first identifying the primary motor cortex may be accomplished without risk of permanent loss of motor activity or speech function, despite the initial severe deficits.
Heterotopic pancreas is a relatively infrequent lesion most often found in the stomach. Four histologic types are recognized: total, canalicular, exocrine, and endocrine heterotopia. To our knowledge, only 2 cases of purely endocrine heterotopic pancreas have been reported in detail. We describe the case of a patient with gastric and duodenal ulcers and gastric endocrine heterotopia. The lack of mass formation, histomorphology, and immunohistochemical features simulating islets of Langerhans supported the diagnosis. We conclude that purely endocrine heterotopic pancreas is a very rare entity that, when present, can simulate a primary or metastatic neuroendocrine tumor. Adequate sampling of the specimen, histomorphologic pattern, and immunohistochemistry are important for the purpose of distinguishing between a neuroendocrine tumor and purely endocrine pancreatic heterotopia.
One hundred twenty-four cases of renal cell carcinoma treated at Department of Urology, The University of Tokyo were analyzed for their clinical characteristics and prognosis. To be noted were the recent increase of incidentally detected cases, kidney-sparing technique in curative surgery and adjuvant therapy using biological response modifiers. Prognosis was more favorable in cases with incidental detection, normal ESR or cystic pattern in pathological architecture, whereas that of cases with metastatic lesions or Grade 3 tumors was ominous. Tumor stage as TUMV or Robson stage was useful to predict the prognosis, although one stage contained cases of considerably different survival periods. These results suggested that the efforts to improve prognosis in the present practice should include early detection of renal cancer by promoting health check-up and development of preventive measure of postoperative recurrence. A more proper staging system might also be needed to analyze clinical studies.
OBJECTIVE: To identify the clinical features in osteosarcoma and to investigate their influence on the prognosis of children and adolescents presenting this disease. MATERIAL AND METHODS: The records of children and adolescents with osteosarcoma treated by the Bone Tumors Group of the state of Rio Grande do Sul, Brazil, between January 1992 and December 2001 were reviewed. RESULTS: Fifty consecutive patients were included in this study. Mean age at diagnosis was 13 years (3-22); 68% of the patients were males. The primary site of disease was the femur in 50% of the patients, tibia in 30%, pelvis in 4%, humerus in 10%, fibula in 2% and other sites in 4%. Nineteen patients presented metastases at diagnosis (38%). All patients received chemotherapy and were treated with three different schemes. As for surgical treatment, 26 patients (52%) had an amputation and 17 (34%) received conservative surgery. Serum lactic dehydrogenase > 1,000 UI/ml (p = 0.0159, log rank), tumor necrosis < 90% and presence of metastases had a negative influence on prognosis. The overall 5-year survival was of 33.2+/-7.2% with mean follow-up of 36 months (6-126). Event-free survival was 29.7+/-7%. The 5-year event-free survival in non-metastatic patients was 45+/-10.7%, and zero in metastatic patients (follow-up of 78.4 and 18.7 months, respectively). Only two out of 19 metastatic patients are alive and free of disease at 18 and 30 months respectively. CONCLUSION: Metastatic disease at diagnosis, serum levels of serum lactic dehydrogenase > 1,000 UI/ml and tumor necrosis < 90% are predictors of unfavorable prognosis. The excessively high incidence of metastatic patients may suggest the presence of an aggressive pattern of disease in our population, or may indicate late diagnosis.
We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.
Lonidamine belongs to a new class of antineoplastics agents, since it does interfere with cell energy processes. When administered as single agent in metastatic breast cancer, it produces moderate therapeutic effects. The pattern of toxicity includes myalgias, asthenia, testicular pain, and gastrointestinal discomfort. No myelosuppression was demonstrated in phase I-II studies. Since the peculiar mechanism of action and side effects are not overlapping with those of standard chemotherapeutic agents, combination of lonidamine with chemotherapy is currently under investigation in advanced breast cancer. Moreover, the potentiation of radiotherapy by lonidamine could be of interest in palliating symptomatic lesions from breast cancer.
Plasminogen activators (PAs) present in the plasma of BALB/c mice and produced in vitro by murine tumor cell cultures (B77-3T3, SR-BALB, AA6) have been characterized using electrophoretic-zymographic techniques. BALB/c mouse plasma contains a main PA activity with an approximate molecular weight of 88,000 and pI 6.3, inhibited by anti-human tissue-type plasminogen activator (t-PA) serum, here defined as murine t-PA. On the contrary, all tumor cells tested release a PA activity with a molecular weight of 44,500 and pI 9.2 characteristic of urokinase-type activator (murine u-PA). The injection s.c. of the different tumorigenic cells into BALB/c mice leads to tumor development and to a rapid increase of t-PA from the first day following the injection. This early enhancement of t-PA activity is not detectable in mice given injections of lethally irradiated B77-3T3 cells. Moreover the development of the tumor in the animals is related to the appearance of increasing levels of u-PA in the blood. This activity is detectable in the plasma of treated mice almost 2 wk before detection of a tumor 1 mm in diameter. During tumor development, the molecular weight of the u-PA and t-PA forms present in the plasma does not change, while there is a decrease of the isoelectric point of the u-PA leading to the appearance of distinct PA activities with pI 7.6 and 8.9. Syngenic and allogenic lymphocytes, injected in BALB/c mice, do not induce any modification in the pattern of the plasma PA. The injection of highly metastatic cells, as opposed to nonmetastatic or low-metastatic cells, does not give rise to detectable levels of u-PA in the plasma of treated mice. These data suggest that the lack of plasma u-PA activity facilitates the formation of metastates, while the increase of this activity is important in tumor development and is independent of the metastatic potential of the injected cells.
The lung is a frequent site of hematogenous metastases of many diverse tumors including soft-tissue sarcoma. The authors present a case with unilateral metastatic spread presenting as a giant lung mass, a pattern which, to the authors' knowledge, has not been reported in the literature.
Breast and lung cancer patients showed certain changes in the cellular patterns of intact regional lymph nodes in cases of metastatic involvement of nodes in adjacent areas. Such changes suggest further search for metastases in the zone of regional metastatic spread.
A 47-year-old man, whose chief complaint was massive hematoemesis, was underwent partial gastrectomy. The resected stomach revealed a large elevated tumor, Borrmann I type, measuring 4 X 3 X 2 cm, in the anterior wall of the body. Histologically, the major part of the tumor showed a sarcomatous structure, while the margin and some areas consisted of papillary or well differentiated adenocarcinoma, invading to the submucosa. The border between the two components was irregular and the two components intermixed with each other in some areas. In the sarcomatous area, there was no bone, cartilage or muscle. It was interesting that the metastatic lymph nodes disclosed a sarcomatous picture with teratomatous pattern and that immunocytochemically HCG was localized in some of the adenocarcinoma in the lymph node.
The gastrinoma was first described in 1955 by the surgeons Zollinger and Ellison. The basic characteristic of this disease is an endocrine tumor of the gastrointestinal tract, which secretes gastrin. There is a hypersecretion of gastric juice and recurrent gastric, duodenal and jejunal ulcers. Herein, the case of a 49 year-old female is presented. In 1982, two liver tumors, sized 10 and 6 cm, were discovered in the right and left lobes of the liver, respectively. A duodenal ulcer was also found. During explorative laparotomy, a liver biopsy specimen was obtained and defined pathohistologically as a metastatic, small cell epithelial tumor with an organoid endocrine pattern, morphologically corresponding to tumors of the APUD (Amine Precursor Uptake and Decarboxylation) series. The gastrinoma was verified by immunohistochemical staining. Serum gastrin values exceeded normal values by 10 times. The patient refused further treatment at that time. In the following years, she was treated conservatively several times for sequelae of ulcer disease. For the past three years, she has been treated as an outpatient, mostly for chronic diarrhea.
BACKGROUND: The utility of performing whole-body bone scintigraphy (BS) as part of a routine staging workup for patients with renal cell carcinoma (RCC) is currently being debated. This study investigated the diagnostic performance of BS in 36 patients with a high pretest probability for bone metastases due to abnormal laboratory tests, pain, or confirmed nonosseous metastases. METHODS: Planar whole-body BS was performed in all patients 3 hours after the intravenous injection of 555 MBq (15 mCi) of technetium-99m-3,3-diphosphono-1,2-propane dicarboxylic acid tetrasodium salt). RESULTS: In 14 of 36 patients, bone metastases could be confirmed either due to computed tomography or magnetic resonance imaging (n=11) or open site directed biopsy (n=3), respectively. The sensitivity ranged from 10% to 60%, depending on the applied visual threshold. The extent of the metastatic involvement was underestimated in all cases. No diagnostic pattern of tracer accumulation, clinical features, or laboratory tests was identified as enhancing the sensitivity for the detection of bone metastases in this population. CONCLUSIONS: The authors concluded that, even among preselected patients, BS has no diagnostic role in RCC and should therefore be omitted from the clinical workup.
In the present study, we assessed whether the pattern of postoperative recurrence of non-small-cell lung cancer differed between patients with pathologic N0 disease and those with pathologic N2 disease. We reviewed 231 patients with pathologic N0 disease and 63 with pathologic N2 disease, who had undergone a complete resection from 1980 to 1990, and investigated the first recurrence sites. Seventy-two patients with pathologic N0 disease and 52 with pathologic N2 disease were found to have had postoperative recurrence. Both pathologic N0 disease and pathologic N2 disease recur frequently in distant organs, and the ratio of distant metastasis to local recurrence did not differ between the two diseases. The brain, lung, and bone were the common initial metastatic sites in both pathologic N0 disease and pathologic N2 disease. The brain was the most frequent site of distant metastasis in patients with pathologic N0 disease, whereas, on the other hand, pulmonary metastasis was observed more frequently than brain metastasis in those with pathologic N2 disease. Despite histologic types, the presence of different patterns of initial metastatic sites between pathologic N0 and pathologic N2 diseases was observed. Our results suggest that the sites of metastasis after resection depend largely on such anatomic factors as drainage routes. Namely, in contrast to pathologic N0 disease, pathologic N2 disease has an additional drainage route, which is from the N2 nodes to the superior vena cava (pulmonary circulation). Therefore, the frequency of pulmonary metastasis may increase in patients with pathologic N2 disease.
It is occasionally difficult to differentiate between multiple primary and metastatic tumors in case of multiple carcinomas. p53 gene mutation pattern by PCR-SSCP and a clonality analysis on the human androgen receptor gene (HUMARA) in multiple tumors were used to distinguish whether carcinomas were multiple primary tumors or a metastasis. Three female patients with multiple carcinomas, who had undergone surgical resection, were selected for these analyses as typical candidates from 11 cases tested. In the first case with bilateral breast cancer the combined analyses were performed on DNA extracted from tumor portions in paraffin sections of each tumor sample and the results indicated that the carcinomas consisted of a primary carcinoma and metastatic tumors. The carcinomas in the second patient consisted of multiple primary carcinomas and the tumors in the third patient consisted of two independent primary carcinomas with different clonal origins. Thus a combination of p53 gene mutation analysis and clonality analysis on HUMARA provided useful, reliable evidence which can help in discriminating multiple primary tumors from metastatic tumors.
Clinico-radiological profile of 25 patients with mediastinal lymphadenopathy due to tuberculosis, Hodgkin's lymphoma and metastases is presented. The main objective was to study the signal intensity pattern of the mediastinal lymph nodes both in plain and contrast enhanced magnetic resonance imaging (MRI), and find out its potential value in the diagnosis. Fifteen patients of tuberculous mediastinal lymphadenopathy, 5 patients of Hodgkin's lymphoma and 5 patients of metastatic lymphadenopathy were studied by 1.5 T Siemens, Magnetom. Both intensity and enhancement pattern were evaluated. Tuberculous lymph nodes appeared isointense in both T1WI and T2WI. On contrast administration multiple hypointense foci were seen in 14 out of 15 patients. The metastatic lymph nodes revealed solitary or multiple hyperintense central foci in T2WI, whereas the lymphomatous lymph nodes revealed heterogenous intensity. Though the lymphomatous nodes revealed mild to moderate type of enhancement, the metastatic nodes revealed dense enhancement of the multiple foci which were seen in noncontrast images. Hence, the MR characteristics of the mediastinal nodes may be useful index in evaluating the aetiology of the mediastinal lymphadenopathy.