Molecular biologic markers and cancer risk assessment

BACKGROUND: Malignant melanoma is the second most common vulvar malignancy. The superficial inguinal lymph nodes are the main site of metastases. Endometrial metastasis of vulvar malignant melanoma has not been previously reported. CASE: Vulvar malignant melanoma was diagnosed in a 60-year-old, postmenopausal woman. Immunohistochemical stains were positive for vimentin and S-100 protein and negative for HMB-45. Six months following vulvectomy, right inguinal lymphadenectomy and immunotherapy, curettage was performed due to postmenopausal bleeding. Histologic and immunohistochemical examinations revealed metastatic malignant melanoma with the same staining reactivity as the primary vulvar neoplasm had. Hysterectomy and bilateral salpingo-oophorectomy was performed, disclosing invasion of the endometrium and the inner two thirds of the myometrium. CONCLUSION: Only 10 other cases of endometrial metastases from malignant melanoma have been previously reported. All those cases involved a primary tumor occurring in the trunk and extremities. This is presumably the first report on endometrial and myometrial metastases from vulvar malignant melanoma.     

Malignant vascular tumors in young patients

BACKGROUND: To the authors' knowledge there are few published series of malignant vascular tumors in patients age < or = 21 years. METHODS: The authors retrospectively documented the clinical presentation, pathology, treatment, and outcome of patients age < or = 21 years with malignant vascular tumors treated between 1970-1995 at Memorial Sloan-Kettering Cancer Center. The histologic sections were rereviewed to confirm the diagnosis. RESULTS: Four patients were identified with angiosarcoma and two with malignant hemangioendothelioma. Five patients were female and one was male; the median age at diagnosis was 11.8 years (range, 8 months-21 years). The tumor involved the skin in one patient, soft tissue in one patient, bone in two patients, and internal organs in two patients. One patient had associated diffuse angiomatosis and another had the Klippel-Trenaunay-Weber syndrome. This patient received prior radiation therapy to the primary site with the subsequent development of a vascular sarcoma. None of the patients had distant metastases at diagnosis. Resection was attempted in five patients and completed in four. Chemotherapy alone was given to three patients whereas radiation therapy alone and radiation plus chemotherapy were administered to one patient each. The median follow-up was 4.9 years (range, 1 month-12 years). There were three deaths from progressive disease and two deaths from locoregional recurrences. Reexcision and radiotherapy controlled one local recurrence. Another patient developed recurrence to regional lymph nodes and further dissemination. The primary tumor in all three survivors was excised completely whereas two of the three patients who died of progressive disease underwent an incomplete excision or biopsy alone. CONCLUSIONS: Malignant vascular tumors are rare in the first two decades of life and when they do occur are very aggressive. Complete resection is curative for patients with localized lesions.     

Different left ventricular relaxation parameters in isolated working rat and guinea pig hearts. Influence of preload, afterload, temperature, and isoprenaline

Six primary lung tumors with numerous multinucleated osteoclast-like giant cells (OLGCs) and no osteogenic component were evaluated histologically and immunohistochemically to examine pulmonary lesions inciting an OLGC response. The patients comprised four women and two men ranging in age from 61 to 80 years (average age, 69 years). The tumors consisted of one adenocarcinoma, two sarcomatoid carcinomas, and three giant cell variants of malignant fibrous histiocytoma. One tumor was endobronchial in location, while five were situated peripherally. Tumor diameter spanned from 1 to 6.5 cm (average, 2.7 cm). In addition to the giant cells, common characteristics included the malignant nature of the neoplasms and, in five of six cases, histologically malignant mesenchyme. This array of cases exemplifies the variability of lung lesions which may elicit an OLGC inflammatory response resulting in areas resembling the giant cell variant of malignant fibrous histiocytoma. The results of this study suggest that OLGCs occur preferentially in malignant rather than benign nonosteogenic lung tumors and that sarcomatoid regions of malignant tumors are more likely to be infiltrated by OLGCs than epithelial regions.     

Ultrasonographic diagnosis of the parotid gland tumors--experience with 310 patients

The diagnostic value of ultrasonography of parotid gland tumors is to determine if the tumor is benign or malignant. In the period from 1984 to 1995, ultrasound examinations were performed on 310 patients with a space-occupying lesion of the parotid gland, using real time 3.75 MHz, 5 MHz and 7.5 MHz transducers. From a histological standpoint, there were 246 benign tumors, namely 144 pleomorphic adenomas, 35 adenolymphomas, 23 other adenomas, 14 cysts, 9 neurinomas, 3 lymphomas, 9 hemangiomas, 3 lymphangiomas and 6 lymph nodes. Another 64 were malignant tumors, namely, 7 mucoepidermoid carcinomas, 7 acinic cell carcinomas, 7 adenoid cystic carcinomas, 15 adenocarcinomas, 7 squamous cell carcinomas, 4 undifferentiated carcinomas, 10 carcinomas in pleomorphic adenoma, 3 malignant lymphomas, 2 metastatic carcinomas and 2 other carcinomas. According to our criteria for ultrasonographic diagnosis of the parotid gland tumors, the benign or malignant pattern was determined by the following findings; shape, boundary echo, internal echo and posterior echo. But in some cases we could not differentiate the two echogram patterns, and we call them the intermediate pattern. The total accuracy rate of the diagnosis of the 310 patients was 79.0%. (The intermediated pattern was found in 39 patients and these cases were considered to be misinterpreted.) In 268 primary parotid gland tumors (210 benign and 58 malignant tumors) excluding recurrent cases, lymph nodes, hemangiomas and so on, the sensitivity was 62.1%, the specificity was 91.4% and the total accuracy rate was 85.1%. The accuracy of sonography in determining whether a tumor was benign or malignant was affected by the tumor size; tumors smaller than 2 cm in diameter showed a tendency to be diagnosed as benign and tumors larger than 6 cm in diameter as malignant. In the 268 cases, the importance of the pattern of the boundary echo and the internal echo in differentiating benign and malignant tumors was examined retrospectively. In the 210 primary benign tumors, the benignity of the tumors was assessed correctly in 84.3% by the boundary echo and 85.7% by the internal echo. In the 58 primary malignant tumors, the malignancy was assessed correctly in 58.6% by the boundary echo and 43.1% by the internal echo. Strong echos, which are the signs of a malignant pattern, were seen in 14.8% of the benign tumors, and in 51.7% of the malignant tumors. It can be concluded that ultrasonography is very reliable for the examination of parotid gland tumors.     

Imaging and pathological features of primary malignant rhabdoid tumours of the brain and spine

In this article two cases of primary malignant extrarenal rhabdoid tumour are described. In the affected children the brain and the spinal cord were the primary sites of origin of the tumour. The imaging findings are presented and the pathology discussed. Although the imaging features are non-specific, rhabdoid tumour should be included in the differential diagnosis of childhood intracranial and spinal neoplasms.     

Colonic carcinoma metastasis to ovary having serous cystadenocarcinoma -- an unusual case of double ovarian malignancy

The ovary is a common site of both primary and secondary tumours. It may be the seat of simultaneous presence of more than one tumour. Often a combination of a malignant tumour is seen within the ovary harbouring a benign tumour. Simultaneous presence of two malignant tumours is rare. Here we describe a 43 year old woman presenting with a simultaneous metastatic adenocarcinoma (primary in colon) along with a papillary serous cystadenocarcinoma of the ovary.     

Primary mesenchymal tumors of the urinary bladder. A histological and immunohistochemical study of 30 cases

The light microscopic and immunohistochemical features of 30 primary mesenchymal neoplasms of the urinary bladder are reported. Half of the cases represented smooth and striated muscle tumors (five leiomyomas, seven leiomyosarcomas including epithelioid and myxoid subtypes, one rhabdomyoma, one embryonal rhabdomyosarcoma and one alveolar rhabdomyosarcoma). One third of the tumors were of fibrohistiocytic origin (one fibrous histiocytoma and eight malignant fibrous histiocytomas including fascicular and storiform, inflammatory and pleomorphic subtypes). In addition, a malignant epithelioid schwannoma, a round cell liposarcoma, two hemangiomas and two mixed mesodermal tumors were observed. The morphology of the vesical mesenchymal tumors was identical to that of their counterparts known to occur in other sites, particularly in the soft tissue. Muscle-specific actin, alpha-1-antichymotrypsin, S-100-protein and neuron-specific enolase proved to be useful and reliable immunomarkers for differential diagnosis of poorly differentiated leio- and rhabdomyosarcomas, malignant fibrous histiocytomas and malignant schwannomas. Since some tumors coexpressed several classes of intermediate filaments, diagnostic immunocytochemistry should only be used considering a larger panel of antibodies and in close correlation with the histological and cytological features of the neoplasms.     

Tonic stretch reflexes in older able-bodied people

OBJECTIVE: An epidemiologic study of multiple primary malignant neoplasms i endometrial cancer patients is presented. DESIGN: From 1984-1996 121 endometrial carcinomas have been evaluated in the Department of Gynecology & Obstetrics in Hospital of S?upsk retrospectively. All double and triple neoplasms have been histologically recorded, doubtful cases have been excluded. MATERIAL & METHODS: Of 121 endometrial carcinomas 12 (9.9%) were multiple malignant neoplasms. Of these neoplasms 7 (5.8%) occur together with breast cancer and 5 (4.1%) with other primary malignomas, 11 are double, 1 is triple malignomas. During the 12-year period of study, 23 patients (19.0%) out of 121 patients diagnosed as having endometrial cancer had another primary benign neoplasms. Of these neoplasms 19 (15.7%) occur together with leiomyomas of uterus and 4 (3.3%) with ovarian cysts. The relation of endometriosis to endometrial carcinoma has been subject of only few studies. The investigations have resulted on the association between the conditions. Endomeriosis was found in association with endometrial carcinoma in 12 (9.9%) of 121 cases. In two cases of endometriosis carcinoma developed. CONCLUSION: There is not statistically significant difference in survival rate between group with synchronous primary malignant neoplasms and group with second primary benign neoplasms or group without multiple primary neoplasms (p = 0.07). Patients with endometrial cancer should be carefully and regularly followed up by monitoring at every anatomic site, especially the breast, stomach, and colon, in order that the development of a second primary carcinoma can be detected as early as possible, and not be overlooked in examinations.     

Induction of whole body hyperthemia with venovenous perfusion

Primary aldosteronism is associated with low plasma renin levels, whilst malignant phase hypertension is generally associated with raised renin activity. These two conditions are therefore at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. We describe in detail 3 cases of primary hyperaldosteronism from a disease register of 315 cases of malignant hypertension seen in one medical centre over 29 years.     

Premorbid hair growth over the trunk and severity of alcohol-related liver disease

OBJECTIVE: To evaluate the clinicopathologic features of malignant pleural effusions secondary to pulmonary adenocarcinoma in patients who have undergone surgical resection of the primary tumor. STUDY DESIGN: Clinical, pathologic and cytologic material from 19 patients who developed malignant pleural effusions after resection of pulmonary adenocarcinoma was reviewed. RESULTS: Malignant effusions developed only in patients with either lymph node or pleural involvement by neoplasm. Time to development of the effusion after resection and overall survival correlated with histologic findings. Malignant effusions in patients who survived > 24 months were secondary to another primary tumor (either breast or a new pulmonary carcinoma). Malignant effusions developed significantly sooner after resection (mean 5.0 +/- 2.0 months, median 5) in patients with lymph nodal metastases than in those with pleural involvement by neoplasm (mean 11.2 +/- 2.5 months, median 12) (Student's t test P = .01, Mann-Whitney U test .04). Nevertheless, survival after resection for patients with lymph node involvement (mean 9.0 +/- 3.6 months, median 8) and those with pleural involvement (mean 12.3 +/- 2.5 months, median 12) was not significantly different. CONCLUSION: Malignant effusions developing in patients more than two years following resection of a pulmonary adenocarcinoma are likely to be secondary to another primary neoplasm. Lymph node and pleural involvement at the time of resection are risk factors for the development of a malignant effusion. Patients with lymph node involvement develop malignant effusions sooner than those with pleural involvement, but the overall survival is not significantly different.     

Control of cardiac output in essential hypertension

We reviewed 179 patients who had undergone thoracotomy and resection of a suspected malignant coin lesion of the lung over the past 20 years to see if a policy of early thoracotomy was therapeutically valid. The average diameter of all lesions was 1.6 cm; the average diameter of 27 malignant lesions (15 percent) was 1.8 cm. Follow-up of the 27 patients with malignant neoplasms was 100 percent. The present survival rate of the 19 patients with primary lung cancer is 89 percent (17/19). Of 12 cases of primary lung cancer followed for five years, ten (83 percent) survived. The five-year survival of the eight patients with metastatic lesions was 25 percent (2/8). There were no postoperative deaths and few serious postoperative complications (four patients or 2 percent). Very small primary lung cancers detected and treated early do have the same poor prognosis as larger primary cancers.     

Mapping of chromosome 3p deletions in human epithelial ovarian tumors

Epithelial ovarian tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of tumor suppressor genes within the deleted regions. We have recently established a primary tissue culture system as a model to investigate the genetic events associated with ovarian cancer. The frequencies of loss of heterozygosity (LOH) at 16 loci representative of chromosome 3p in 33 tumor biopsies and 47 ovarian primary cultures derived from unselected ovarian cancers were examined. This repertoire also included benign and borderline tumors as well as malignant ovarian ascites. LOH was observed in 25 (31%) samples for at least one marker: 21 of 58 malignant, two of 12 borderline and two of 10 benign specimens. Chromosome 3p loss was not restricted to ovarian tumors of high grade and stage. LOH was observed in both cultured and non cultured tumors and ascites. A spontaneously immortalized cell line derived from a malignant ovarian ascites, OV-90, displayed LOH of the majority of markers suggesting loss of one homolog of chromosome 3p. The pattern of deletion displayed by these 25 samples enabled the determination of at least two distinct regions of overlapping deletions on chromosome 3p extending from D3S1270 to D3S1597 and from D3S1293 to D3S1283. In addition, a region proximal to D3S1300 was deleted in a subset of samples. Although loss of loci overlapping these three regions (Regions I, II and III) were observed in malignant and benign tumors, in borderline tumors loss was observed of markers representative of Region III only. While RARbeta is presently included in Region II, the minimal regions of deletion exclude VHL, TGFBR2, PTPase(gamma) and FHIT as candidate tumor suppressors in ovarian tumorigenesis.     

Malignant glaucoma induced by miotics postoperatively in open-angle glaucoma

A case of malignant glaucoma that developed in a patient with primary open-angle glaucoma is described. The malignant course was induced during the immediate postoperative period by the inadvertent use of miotics. The malignant course was successfully managed by osmotic agents, acetazolamide, cycloplegics, mydriatics, and topical steroids.     

Primary dedifferentiated leiomyosarcoma of the fallopian tube

Between 1960 and 1995 the University of Leipzig Women's Hospital encountered 44 cases of primary malignant tumors of the Fallopian tube, including four malignant Müller mixed tumors and one sarcoma. The sarcoma, a dedifferentiated leiomyosarcoma, was found incidentally in a 57-year-old woman. Treatment encompassed total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy and pelvic and para-aortic lymph node dissection, followed by telecobalt irradiation of the pelvis (Hd 52 Gy). One year after treatment, no evidence of disease recurrence, is found. Literature documents only 34 cases of a primary uterine tube sarcoma. Even with RO-resection, the early, high rate of local recurrence (most often within the first two years after treatment) and hematogenous metastasis to the lungs, liver and bones compose this tumor's clinical course. The prognosis is poor despite the use of radiotherapy and/or combination chemotherapy.     

Adrenal pheochromocytoma with both benign and malignant components

A case of adrenal pheochromocytoma is reported characterized by polygonal basophilic granular cells of benign type, plump eosinophilic granular cells of transitional type, and spindle-shaped cells of malignant type. In the primary tumor the neoplastic cells of each type revealed a distinctive topographical distribution. All gradations between the latter two varieties of cells were found, especially in the vicinity of the transitional cell area. Multiple metastases were present in the liver and lungs, where only anaplastic spindle-shaped cells could be found. Ultrastructurally, the benign cells contained predominantly large, rather light, secretory granules with a coarsely granulated core. In the malignant cells, the number, size, and intensity of granules varied considerably from cell to cell or even within a single cell. In general, the malignant cells had a higher frequency of smaller granules with electron-dense homogeneous cores. Moderate amounts of noradrenalin but not significant dopamine or adrenalin could be demonstrated from a metastatic nodule in liver. We postulate that this adrenal medullary pheochromocytoma was benign originally and underwent malignant transformation shortly before the patient's death. This is based upon the patient's clinical features and the peculiar structures of the primary tumor.     

Muscle amino acid metabolism and the control of muscle protein turnover in patients with chronic renal failure

Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h d(-1), 5 days per week for 65 weeks to one of two concentrations of natural uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant radon content. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime. Lung uranium burdens, measured at the time of death of each animal, declined exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. Lymph node specific burdens ranged from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed groups, respectively. There was no difference in tumor latency between the groups. Absorbed dose to the lung was calculated for each animal in the study. The average doses for all the animals exposed to the low and high dust aerosol concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both groups. The frequency of primary lung tumors was also calculated as a function of dose increment for both exposed groups individually and combined. The data indicate that, in spite of the above result, lung tumor frequency was not directly proportional to dose. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting dose rate may be a more important determinant of lung cancer risk than dose. Conversely, non-malignant lung tumors were significantly correlated with low lung burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation and that malignant tumor risk was not directly proportional to dose, but was directly proportional to dose rate.     

Intraocular cancers

1. Retinoblastoma is the most common primary intraocular cancer of children. It occurs in unilateral and bilateral forms. 2. Approximately 40% of all cases are associated with a heritable defect in chromosome 13. 3. Malignant melanoma is the most common primary intraocular malignant tumor among adults. 4. Unlike retinoblastoma, primary intraocular malignant melanoma is almost exclusively a monocular, unifocal disease without hereditary transmission.     

Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated with low level of parasitaemia and mimicking malignant histiocytosis

The ultrastructural features of histiocytes in the bone marrow (BM) were studied in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed by one of us as visceral leishmaniasis (VL) associated with low level of parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and ultrathin (SUT) sections showed that the BM was hypercellular and markedly infiltrated by large histiocytes with prominent phagocytosis. A thorough examination of various ST and UT section revealed only a single, typical Leishman-Donovan body. At transmission electron microscopy (TEM) level, two principal types of histiocytic cells were identified: Type I, subdivided into two subtypes, were actively phagocytic histiocytes (PH) with large digestive vacuoles and primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction between the PH and ingested cells is described. Both types of cell were morphologically similar to previously described malignant histiocytic cells. However, this study showed a better characterization of PH during VL.     

Malignant neoplastic disease of the parotid lymph nodes

OBJECTIVES: To review the management and outcome of patients with malignant neoplastic disease of the parotid lymph nodes excluding those with primary salivary gland tumors. STUDY DESIGN: Retrospective review of 14 patients who had malignant parotid lymph nodes from metastatic cutaneous malignancies, direct extension from primary cutaneous malignancies, or lymphoproliferative disorders. METHODS: Charts were reviewed from three institutions and tabulated for age, gender, histopathology, treatment, and outcome. RESULTS: Fourteen patients met the criteria for study. Ten patients had neoplastic nodes from cutaneous malignancies. Seven involved squamous cell carcinoma, two were metastatic from melanoma, and one was metastatic from basal cell carcinoma. Four patients had involvement from lymphoproliferative disorders. CONCLUSIONS: Metastatic disease to the parotid nodes or direct extension to nodes from primary cutaneous malignancy demonstrates a poor prognosis in this series. Prognosis of lymphoproliferative disorder is more favorable.