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Intraabdominal desmoplastic small-cell tumors with divergent differentiation. Observations on three cases of childhood.

We studied three intraabdominal tumors that manifested in childhood and were attached to peritoneum, and in which the histologic pattern suggested metastatic tumor of epithelial nature but gave no evidence of a primary neoplasm in the major abdominal organs. Follow-up observation lasted from 1 to 6 years but never disclosed a primary site. Histologic, immunohistochemical, and electronmicroscopic observations indicated a primitive malignant neoplasm of uncertain histogenesis capable of simultaneously expressing epithelial, mesenchymal, and, less consistently, neural phenotypes. In childhood, the possibility of embryonic neoplasm, such as nephroblastoma occurring in atypical sites, is difficult to exclude. Despite the prevailing uncertainty about histogenesis, combined therapy achieved an apparent cure in one of our cases.

Abdominal Neoplasms↗

Metastatic granulosa cell tumor with pattern of sex cord tumor with annular tubules.

A case of malignant, complex sex cord tumor with multiple differentiations in a 38-year-old woman is presented. The neoplasm presented originally as a pure granulosa cell tumor, and in the second look operation as a sex cord tumor with annular tubules (SCTAT). Six years later abdominal metastases revealed a mixed pattern of granulosa and Sertoli cell tumor admixed with SCTAT. The patient died despite chemotherapy. Analysis of the 10 previously reported cases of malignant SCTAT shows that tumor size is the main prognostic indicator. Mitoses, atypia, and stromal invasion seem also to bear prognostic implications when present. The association of both granulosa and Sertoli cells with SCTAT seems to provide a clue for SCTAT being a peculiar intermediate phenotypical expression of pluripotential stem sex cord cells of the gonads.

Adult↗

CT and US findings of pancreatoblastoma.

PURPOSE: Our goal was to evaluate US and CT findings of pancreatoblastoma. METHOD: Three US and four CT scans before surgery and one follow-up CT after surgery were reviewed in four patients (two female, two male) with pathologically proven pancreatoblastoma. The mean age of the patients was 4 years (range 2-5 years). The masses were analyzed for origin, US and CT architecture, presence of calcification, enhancement pattern, and metastatic spread. RESULTS: In two patients, the tumors arose from the pancreatic head and in one patient from the pancreatic tail. The mean largest diameter of the masses was 10 cm, ranging from 5 to 14 cm. Sonography obtained from three cases showed mixed echogenic solid mass. On the CT scan, all tumors were huge, lobulated masses with heterogeneous attenuation. One tumor contained numerous foci of calcification. On the enhanced CT scan, three tumors showed multiloculated appearance by enhancing internal septations. There was no evidence of metastasis to distant organ or abdominal lymph node in any case. CONCLUSION: We suggest that the most common US finding of pancreatoblastoma is a mixed echogenic, solid mass inseparable from the pancreas, and the most common CT finding is a relatively well defined, lobulated, huge mass with multiloculated appearance by enhancing septae in or near the lesser sac.

Child, Preschool↗

Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study.

PURPOSE: Previous studies demonstrate a positive correlation between postoperative survival and the extent of pelvic lymphadenectomies in patients with bladder cancer. However, the distribution of nodal metastases has not been examined in sufficient detail. Therefore, we conducted a comprehensive prospective analysis of lymph node metastases to obtain precise knowledge about the pattern of lymphatic tumor spread. MATERIALS AND METHODS: Between 1999 and 2002 we performed 290 radical cystectomies and extended lymphadenectomies. Cranial border of the lymphadenectomy was the level of the inferior mesenteric artery, lateral border was the genitofemoral nerve and caudal border was the pelvic floor. We made every effort to excise and examine microscopically all lymph nodes from 12 well-defined anatomical locations. RESULTS: Mean total number and standard deviation of lymph nodes removed was 43.1 +/- 16.1. Nodal metastases were present in 27.9% of patients. The percentage of metastases at different sites ranged from 14.1% (right obturator nodes) to 2.9% (right paracaval nodes above the aortic bifurcation). By studying cases of unilateral primary tumors or with only 1 metastasis we observed a preferred pattern of metastatic spread. However, there were many exceptions to the rule and we did not identify a well-defined sentinel lymph node. CONCLUSIONS: We strongly recommend extended radical lymphadenectomy to all patients undergoing radical cystectomy for bladder cancer to remove all metastatic tumor deposits completely. The operation can be conducted in routine clinical practice and our data may serve as a guideline for future standardization and quality control of the procedure.

Adult↗

Identifying site-specific metastasis genes and functions.

Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression. Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of primary breast cancers revealed a subset of site-specific metastasis genes that are selected for early in tumor progression. High expression of these genes predicts the propensity for lung metastasis independently of several classic markers of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.

Animals↗

Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas.

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. beta 1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue beta 1 integrins were mainly found on resident cells and except for alpha 4, alpha 5 (and beta 1) the lymphoid cells expressed very little, if any, beta 1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.

Cell Adhesion Molecules, Neuronal↗

Neuroblastomas in Denmark 1943-80. Epidemiological and clinical studies.

Two-hundred-and-fifty patients were registered in a population-based study of neuroblastomas in Denmark in the period 1943-80. The major epidemiological findings were an increased incidence with an unchanged mortality rate during the study period. The increase in incidence related solely to children 0-4 years of age and was most pronounced in infants under 1 year of age. Several reasons for the observed epidemiological rates include (i) changes in the composition of the population, (ii) improved diagnostic procedures, (iii) a shift in the diagnostic criteria, and (iv) an increase in environmental carcinogens of importance in the induction of neuroblastoma. Associated with an increased risk were lower socio-economic levels and young or advanced parental age, suggesting the importance of environmental as well as genetic factors for the induction of neuroblastoma. The epidemiological findings of an increased incidence with an unchanged mortality rate, which suggests the inclusion of borderline lesions in recent years, are of major importance in interpreting the results of mass screening for the disease. The clinical findings in 253 patients treated in Denmark from 1943 to 1980 (including 5 patients resident outside Denmark and excluding 2 patients without available hospital records) were analysed. The major finding was a zero-time shift, that is, earlier diagnosis of the disease during the study period, with increasing survival rates from decade to decade mostly due to a better age and stage distribution, a zero-time shift which was also apparent in the changes of the symptomatology. Independent prognostic variables were age, stage, and treatment with chemotherapy for children over 1 year of age with stage II disease, and for infants with stages III-IV disease. Analysis of data from a subset of the 253 children suggested that high proliferative activity detected by flow cytometry may be an important prognostic variable. The study also suggests that the pattern of metastatic spread might have changed as a consequence of prolonged survival obtained by improved treatment modalities, stressing the importance of a high frequency of autopsy among cancer patients. Hypotheses generated by the study included (i) that most neuroblastomas might be congenital, (ii) that the age influence on prognosis might be explained in terms of growth rate, cell cycle transit time, and duration of the disease, and (iii) that some neuroblastomas might be borderline lesions.

Adolescent↗

From the archives of the AFIP. Genitourinary rhabdomyosarcoma in children: radiologic-pathologic correlation.

Rhabdomyosarcoma is the most common tumor of the lower genitourinary tract in children in the first 2 decades of life. Most cases of genitourinary rhabdomyosarcoma are of the embryonal histologic subtype and include tumors of the bladder, prostate, testes and paratesticular sites, penis, perineum, vagina, and uterus. The natural history, pattern of metastatic spread, treatment, and prognosis of childhood rhabdomyosarcoma vary with the anatomic site of the lesion. In children with rhabdomyosarcoma of the bladder or prostate, presenting signs and symptoms include urinary or fecal retention, dysuria, urinary tract infection, and hematuria. Paratesticular rhabdomyosarcoma produces painless scrotal swelling, which may be ignored until the tumor has reached a large size. Vaginal tumors may manifest as a prolapsing mass in the introitus. Radiologic studies of children with genitourinary rhabdomyosarcoma reflect the nonspecific gross features of the tumor, which may be ill defined with infiltrative margins or well circumscribed by a pseudocapsule of compressed tissue. The botryoid variant of embryonal rhabdomyosarcoma results when submucosal tumor produces a polypoid mass resembling a cluster of grapes within a hollow structure. Botryoid morphology is characteristic, but not specific, for rhabdomyosarcoma within the vagina or urinary bladder, since yolk sac tumor and "tumoral" cystitis may have a similar appearance. Invasion of adjacent structures by the primary tumor may make the precise anatomic origin of genitourinary rhabdomyosarcoma difficult to determine on cross-sectional images. Recent refinements in multidisciplinary therapeutic regimens combining chemotherapy, radiation therapy, and surgery have dramatically improved outcome for children with genitourinary rhabdomyosarcoma. Diagnostic imaging plays an important role in monitoring response to therapy.

Adolescent↗

Punctate intranodal gold deposits simulating microcalcifications on mammograms.

Some axillary lymph nodes are frequently seen on mammograms. Rarely, such nodes will demonstrate opacities that appear to be multiple punctate calcific deposits. The literature is of little guidance as to the meaning of this appearance. One report indicates that breast cancers that are manifested as extensive punctate calcifications very rarely occur in this pattern in metastatically involved axillary lymph nodes. The authors suggest that such punctate densities are much more often indicative of intranodal gold deposits and that they occur almost invariably in patients with rheumatoid arthritis who have undergone prolonged chrysotherapy. This observation was confirmed in one patient and suspected in three others with similar clinical histories.

Arthritis, Rheumatoid↗

An unusual cause of irritable urinary bladder symptoms.

A metastasis from a renal cell carcinoma to a seminal vesicle is extremely rare. This pattern of metastatic disease has been reported once previously in the Japanese literature. We describe a patient with irritability symptoms of the urine bladder and involuntary loss of stool caused by obstruction of the bladder by a large metastasis from a renal cell carcinoma to the seminal vesicle. The mode of diagnosis and treatment of this patient are described.

Carcinoma, Renal Cell↗

Mediastinoscopy: the predictive survival value in staging carcinoma of the lung.

One hundred and thirty-seven cases of Stage III lung cancer established by mediastinoscopy have been followed to determine their survival. The tissue was classified according to World Health Organization schema and the degree of dedifferentiation graded from well to poorly differentiated. Two percent of the presented cases are well-differentiated tumors; the remaining 98% are moderately well-differentiated (11%), or poorly differentiated or small cell tumors (87%). The degree of anaplasia suggests an increasingly aggressive metastatic behavior pattern. The average life span is approximately 5 1/2 months in all groups and subgroups which were studied. Recommendations are presented for the utilization of mediastinoscopy in Stage I and II cases. Further considerations are suggested for priority of diagnostic procedures in establishing the diagnosis of lung cancer.

Adult↗

Lymph node involvement in locally advanced cervical cancer patients administered preoperative chemoradiation versus chemotherapy.

BACKGROUND: A retrospective study was planned in 127 locally advanced cervical cancer (LACC) to investigate: (1) the rate and pattern of metastatic lymph node involvement in patients administered preoperative chemoradiation (CT/RT) versus neoadjuvant chemotherapy (NACT), and (2) the profile of clinico-pathological parameters predictive of metastatic lymph node involvement in these two clinical settings. Finally, we investigated whether the pathologically assessed status of lower pelvic nodes (LPN) was able to predict the pathologically assessed status of upper pelvic nodes (UPN) and parametrium in cases administered CT/RT. METHODS: Patients were selected including LACC patients who were administered concomitant CT/RT (n = 87) or NACT (n = 40), before radical surgery. RESULTS: Metastatic pelvic lymph node involvement was significantly lower in cases administered CT/RT (11.5%) compared to cases administered NACT (30.0%) (P value = 0.009). In the CT/RT group, only MRI-assessed pelvic node status (both at staging and post-treatment evaluation) was associated with pathologic pelvic node status. In patients administered CT/RT, the status of LPN appeared associated with the status of UPN. CONCLUSIONS: (1) Preoperative CT/RT treatment is associated with a lower rate of pelvic node disease in LACC patients compared to NACT; (2) there is no association between the preoperative extent of residual cervical disease after CT/RT and pathologically assessed pelvic node status; (3) the pathological status of LPN is predictive of the pathological status of UPN and parametrium.

Adult↗

Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes.

This chapter describes the components of the initial evaluation for a patient either suspected or known to have lung cancer. The components of the initial evaluation are based on the recognized manifestations of localized lung cancer, ie, symptoms referable to the primary tumor, intrathoracic spread of lung cancer, and patterns of metastatic dissemination. Features of the history and physical signs may be useful indicators of the extent of disease. A standardized evaluation, relying on symptoms, signs, and routinely available laboratory tests, can serve as a useful screen for metastatic disease. Also described are the common features of the various paraneoplastic syndromes associated with lung cancer.

Clinical Laboratory Techniques↗

Patterns of neoplastic spread in colorectal cancer: implications for surveillance CT studies.

OBJECTIVE: This study was performed to assess patterns of metastatic disease shown on CT in colorectal cancer and to determine the diagnostic yield of routine pelvic CT in follow-up surveillance. MATERIALS AND METHODS: Pathology records and 3073 CT studies of 1119 patients with colorectal cancer were retrospectively reviewed. Primary tumor site, site of abdominal or pelvic metastases (liver, peritoneum, lymph nodes, local recurrence, or other), and incidental nonmetastatic pelvic disease were recorded. The superior iliac crests were considered the border between the abdomen (above) and the pelvis (below). RESULTS: Metastatic disease was present in 34% (1040/3073) of all CT studies: 33% (1007/3073) in the abdomen and 7% (227/3073) in the pelvis. Six percent (194/3073) of studies had metastases in both abdomen and pelvis. Forty-one percent (404/991) of studies showing abdominal primary colonic tumors showed metastatic disease: 40% (400/991) in the abdomen and 8% (78/991) in the pelvis. Four studies (0.4%; 4/991) in four different patients with abdominal primary colon tumors had isolated pelvic metastases; three of these were primary tumors of the cecum. Thirty-one percent (636/2082) of studies showing pelvic primary colonic tumors showed metastatic disease: 29% (607/2082) in the abdomen and 7% (149/2082) in the pelvis. Twenty-nine studies (1%; 29/2082) in 26 patients with pelvic primary colonic tumors revealed isolated pelvic metastases. CONCLUSION: In colorectal tumors arising within the abdomen, pelvic metastases are uncommon and isolated pelvic metastases are rare. Routine pelvic CT performed in the follow-up surveillance of patients with colorectal cancer with primary tumors arising in the abdominal portion of the colon has a low diagnostic yield.

Abdominal Neoplasms↗

The basal phenotype of BRCA1-related breast cancer: past, present and future.

Many BRCA1-related tumors have a distinct histological characteristics which together have been called "basal-like." Typically such tumors are ER-, HER2- and express cytokeratin 5/6, cytokeratin 8/18, EGFR and vimentin. These characteristics can be used to predict which breast cancers are most likely to be associated with germline BRCA1 mutations which has important implications for breast pathologists. Moreover, BRCA1-related breast cancers generally have a poorer prognosis which may paradoxically be more pronounced in node negative cancers. This may relate in part to a different pattern of metastatic spread with in increased frequency of brain and lung metastases in BRCA1 carriers. Conversely, BRCA1-related tumors may respond better to neoadjuvant chemotherapy and their characteristic molecular signature may provide opportunities to develop specific molecular targeted therapies akin to traztuzumab in HER2+ cancers. Finally, many of the phenotypic features of BRCA1-related tumors might also be found in putative breast stem cells and therefore characterization of the BRCA1 breast cancer phenotype will improve our understanding of sporadic breast carcinogenesis.

Biomarkers, Tumor↗

Anatomical pathways of lymphatic flow between lung and mediastinum.

The knowledge of anatomical lymphatic drainage pathways between lung and mediastinum and metastatic spread patterns of lung cancer forms the basis for the modern TNM classification for the staging of lung cancer. Clinical and anatomical studies divided pulmonary nodes into intrapulmonary and bronchopulmonary, the latter distinguished into lobar and hilar nodes. Mediastinal nodes are grouped into anterior prevascular, tracheobronchial, paratracheal and posterior nodes. The different pathways of lymphatic drainage of the lungs to the mediastinal lymph nodes are presented with the consequent surgical implications.

Humans↗

Sclerosis in non-Hodgkin's lymphomata.

A total of 242 cases of non-Hodgkin's lymphoma arising primarily in lymph nodes are reported. Lymph nodes have been classified histologically and the incidence of sclerosis in each group assessed. Two types of fibrosis were found, one composed of fibrous bands from 10 mum to several hundred mum thick within the node and invaded perinodal tissue. The other type was a fine compartmentalizing fibrosis sometimes simulating the pattern of metastatic carcinoma in part of a node, the rest of the node being typical of malignant lymphoma. Both types of fibrosis were present in some nodes. Fibrous bands were present in all histological types, with the exception of the diffuse lymphocytic well differentiated group. Fine compartmentalizing fibrosis was seen only in association with areas of undifferentiated large celled lymphoma. The presence of sclerosis is shown to correlate with a better prognosis when compared with non-sclerosing tymours of similar histological type. That sclerosing lymphomata are more slowly progressive is borne out by the fact that two-thirds of the patients with sclerotic nodes presented with localized disease compared with less than half of the patients whose nodes showed no sclerosis.

Humans↗