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Esophageal cancer. Radiologic diagnosis.

The vast majority of malignant esophageal tumors are either squamous cell carcinomas or adenocarcinomas arising in Barrett's mucosa. This article reviews the spectrum of findings associated with these tumors on barium studies. Particular emphasis is placed on the role of double-contrast esophagography in detecting early cancers, because these lesions have the best possibility for cure. Other less common malignant tumors, such as spindle cell carcinoma, small cell carcinoma, leiomyosarcoma, Kaposi's sarcoma, and malignant melanoma, are also reviewed.

Esophageal Neoplasms↗

Orbital Ewing's sarcoma of the orbit.

PURPOSE: Ewing's tumor is a primary tumor of bone in childhood that only rarely involves the orbit. Most such cases are metastatic from distant sites. This tumor may be confused with other small round cell malignancies of childhood, and immunohistochemical studies are essential in making the diagnosis. METHODS: We present two cases of Ewing's tumor of the orbit. One was in a 22-year-old boy with an occult primary tumor in the frontal bone that became symptomatic after forehead trauma. The other example was in a 7-year-old boy with a known Ewing's primary of the clavicle. The clinical manifestations and diagnostic criteria are discussed. RESULTS: In most cases with orbital involvement, ophthalmic symptoms consist of proptosis, pain, and occasionally visual loss and motility restriction. The diagnosis is typically unsuspected before histologic evaluation. Electron microscopic and immunohistochemical analyses are essential in making the diagnosis and are necessary for all such small round cell tumors. CONCLUSIONS: Ewing's sarcoma is a rare orbital tumor of bone mainly affecting children. Local treatment relying on surgical extirpation and radiotherapy alone has proven inadequate, with 5-year survival rates of <10%. The addition of chemotherapy has improved survival rates significantly to approximately 50%.

Biopsy↗

Osteosarcoma with small cells simulating Ewing's tumor.

Twenty-four patients who had osseous lesions with histological features of both Ewing's sarcoma and osteosarcoma were studied. Because of their appearance, these lesions have been labeled small-cell osteosarcomas. They appear to represent a definite histological entity and the prognosis may be worse for these lesions than for conventional osteosarcomas. It is most important not to misdiagnose this tumor as Ewing's sarcoma because it appears not to be radiosensitive. Radical surgery and modern adjuvant chemotherapy seem to offer the best chance of cure.

Adolescent↗

[Undifferentiated small cell tumor of the thoracopulmonary region].

The group of rounded small-cell tumors include different neoplasias involving different therapies; we can name neuroblastoma, Ewing' sarcoma, embrionary rhabdomyosarcoma, lymphoma and other pathology such as Askin's tumor or small cell tumor of the thorax area. Based on microscopic and immunohistochemistry findings, it is suggested that it originates from the neural crest or pluri-potential cells from the neuroectodermy. This has a very aggressive behaviour and is usually resistant to oncologic therapies.

Adolescent↗

(Sub)periosteal Ewing's sarcoma of bone.

Ewing's sarcoma is a small malignant round-cell tumour that arises from mesenchymal cells, predominantly in the medullary cavity of bone. In exceptional cases it originates in the soft tissues and subsequently invades the underlying bone. A (sub) periosteal origin of Ewing's sarcoma is a very rare condition: only a few cases have been published so far. Three cases of (sub)periosteal Ewing's sarcoma, having received neoadjuvant chemotherapy and radiation therapy as well as wide excision, are reported.

Adolescent↗

Characterization of hamster tumors induced by simian virus 40 small t deletion mutants as true histiocytic lymphomas.

Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.

Abdominal Neoplasms↗

Large unilateral chest tumors in children.

When large unilateral chest tumors are hidden by pleural fluid collections, or when there is a completely radiopaque hemithorax, ultrasonography is an efficient means of identifying and characterizing a mass. Narrowing of the carinal angle in patients with mediastinal shift is helpful in identifying large intrathoracic tumors that could be mistaken for, or hidden by, large pleural effusions. Of 11 large tumors in children, seven were Ewing's sarcomas, two were metastatic sarcomas, one was a lymphoma, and one was an undifferentiated small cell tumor of unknown origin. The rib lesions of Ewing's sarcoma were seen clearly on chest radiographs in all patients with that disease.

Adolescent↗

Chest wall tumors in infants and children.

Chest wall tumors are infrequent in infants and children, but a high proportion of these tumors are malignant. They present most frequently as a palpable mass, and less frequently with pain or respiratory distress. Radiographic evaluation should include chest radiographs followed by computed tomographic (CT) scan. In most cases an initial incisional biopsy is performed because of the significant risk of malignancy. The most frequent tumors are the malignant small round cell tumors (Ewing's sarcoma/primitive neuroectodermal tumor [PNET] family) followed by rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and a spectrum of other sarcomas. Initial treatment with chemotherapy, particularly for the malignant small round cell tumors and osteosarcoma, may facilitate resection by decreasing the size of the tumor as well as its vascularity and friability. Cure requires successful local control and adjuvant chemotherapy and is particularly difficult to achieve in children presenting with metastases.

Child↗

Aminoacyl-tRNA synthetases in liver, spleen and small intestine of aged leukemic and aged normal mice.

The specific activities of 17 aminoacyl-tRNA synthetases in liver, lung, heart, spleen, kidney and small intestine of old female normal and leukemic (reticulum-cell sarcoma, type A) mice have been monitored. No difference appears for lung, heart and kidney; small increases with varying particular changes for liver and marked increases in spleen and small intestine of the tumor bearing mice have been found, following a similar pattern. This finding suggests a coordinated adaptation to modulation of the requirements of protein synthesis imposed by histiocytic sarcoma.

Aging↗

Extraskeletal Ewing's sarcoma. Histologic and ultrastructural observations in three cases.

The histologic and ultrastructural morphology of three cases of Ewing's sarcoma of soft tissue are described and the fine structural features of extraskeletal Ewing's sarcoma are compared to those of similar round-cell tumors that are considered in the differential diagnosis. By light microscopy, these tumors are indistinguishable from Ewing's sarcoma of bone. Ultrastructurally, the salient features are also comparable to Ewing's sarcoma of bone and include: 1) absence of surface modifications; 2) cell-contact sites in the form of small thickenings of apposed membranes and large desmosome-like specializations; 3) undifferentiated cytoplasm usually containing abundant glycogen and occasionally nonspecific microfilaments; 4) significant variation in shape and irregularity of nuclear profiles. The ultrastructural features of extraskeletal Ewing's sarcoma are sufficiently distinctive to allow separation from from other small-cell malignant neoplasms in the majority of cases.

Adult↗

Calponin and h-caldesmon expression in synovial sarcoma; the use of calponin in diagnosis.

AIMS: To assess the frequency of expression and potential diagnostic utility of calponin and caldesmon in synovial sarcomas. METHODS AND RESULTS: Immunohistochemistry with antibodies to calponin and h-caldesmon was undertaken in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of which one biphasic and eight monophasic tumours had poorly differentiated areas), 10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for calponin in spindle and glandular areas, nine in spindle cells only, and one in glands only. All monophasic synovial sarcomas and poorly differentiated areas expressed calponin; in monophasic tumours this was focally (29% of cases), moderately (39%), or diffusely (32%) positive and the poorly differentiated areas were usually moderately or diffusely positive. Four synovial sarcomas showed focal reactivity for h-caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT, 4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H-caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5 fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative in the other small round cell tumours. CONCLUSIONS: Calponin can be used as an additional marker for synovial sarcoma. Its absence argues against the diagnosis. The presence of calponin might be useful in distinguishing poorly differentiated synovial sarcoma from other small round cell tumours. H-caldesmon is not helpful in diagnosis of synovial sarcoma.

Biomarkers, Tumor↗

pH and population density in the regulation of animal cell multiplication.

Sparse and dense cultures of chick embryo cells were affected differently by pH. The rates of cell multiplication and of thymidine-(3)H incorporation into DNA of dense cultures were increased as the pH was increased from 6.6 to 7.6. At pH higher than 7.6 the rate of multiplication decreased slightly in the dense cultures, but the rate of thymidine-(3)H incorporation continued to increase. The discrepancy was due in part to cell death and detachment at very high pH, and in part to a more rapid uptake of thymidine-(3)H at very high pH. Sparse cultures were much less sensitive to pH reduction and, when a suitably conditioned medium was used to minimize cell damage, very sparse cultures grew almost as well at pH 6.7 as at higher pH. The rates of cell multiplication and thymidine-(3)H incorporation at low pH decreased in the initially sparse cultures before they reached confluent cell densities. There was no microscope evidence of direct contact between plasma membranes of cells at these densities although the parallel orientation indicated that the cells were influencing locally each other's behavior. Even at much higher cell densities, electron microscopy revealed large intercellular gaps partly filled with a fragmentary electron-opaque material suspected to be glycoprotein. Wounding experiments showed that pH affected cell migration in a manner similar to its effects on cell multiplication. Low pH inhibited cell migration, but those cells which migrated into the denuded region multiplied as rapidly at low pH as at high pH. The effects of pH on growth were correlated with effects on the uptake of 2-deoxyglucose-(3)H. Dense populations of cells inhibited by low pH were stimulated to incorporate thymidine-(3)H by the addition of small amounts of diethylaminoethyl-dextran. Rous sarcoma cells at high cell density were less sensitive to pH than were normal cells at the same density, but were more sensitive than sparse normal cultures. The results suggest that cell growth is inhibited through the combined effects of both lowered pH and high cell density on cell surface permeability.

Animals↗

A pathology-based substrate for target definition in radiosurgery of brain metastases.

PURPOSE: To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. METHODS AND MATERIALS: Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. RESULTS: In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of > or =1 mm, and other histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). CONCLUSIONS: Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of approximately 1 mm should be added to the visible lesion.

Aged↗

[Results of a phase I-II clinical trial of Emoxyl, a novel antineoplastic anthracycline].

Emoxyl (ruboxyl) is a product of chemical modification of daunorubicin mediated by a stable free radical. The drug was given to 63 patients with different malignancies stages I-II. Inhibition of hemopoiesis (leukopenia and thrombocytopenia) was identified as the dose-limiting toxicity level. Alopecia or cardiotoxicity were not reported. A daily single dose of 100 mg/m2, 5 days, repeated in cycles after 3 weeks, proved the safest and most effective. Out of 55 cases evaluated for immediate effect, complete remission (breast cancer, small-cell cancer of the lung, Kaposi's sarcoma)--3; partial remission (breast cancer--2; non-Hodgkin's lymphoma--1)--3, and stabilization--26.

Aged↗

Exfoliative cytology of neuroendocrine small cell carcinoma of the endometrium. A report of two cases.

BACKGROUND: In the female genital tract, neuroendocrine small cell carcinoma can occur in the endometrium as well as the cervix, ovary and vagina. This tumor has a high propensity for systemic spread and a poor prognosis. Small cell carcinoma of the endometrium is cytologically identical to its counterparts in the lung and other sites. Its characteristic appearance in a cervicovaginal smear should raise concern about small cell carcinoma. Other tumors of the uterus should be considered in the differential diagnosis, including adenocarcinoma with neuroendocrine features, small cell nonkeratinizing squamous cell carcinoma, endometrial stromal sarcoma, rhabdomyosarcoma, primitive neuroectodermal tumor, non-Hodgkin's lymphoma and metastatic breast carcinoma. CASES: Case 1 was a 59-year-old, white female, and case 2 was a 47-year-old, white female. Both patients presented with vaginal bleeding. The Papanicolaou smears in both cases had similar, characteristic exfoliative cytology. The tumor cells were small and either single or arranged in groups and files. They had barely visible cytoplasm, darkly staining nuclei with finely stippled chromatin, and inconspicuous nucleoli. The characteristic molding of the nuclei was also present. Immuno-histochemical staining for neuron-specific enolase and synaptophysin was positive in tissue sections. Pancytokeratin, vimentin, muscle-specific actin, desmin, alpha-fetoprotein, S-100, glial fibrillary acid protein, common leukocyte antigen and chromogranin were negative. CONCLUSION: When a uterine small cell carcinoma is suspected in a cervicovaginal smear, the similarity of cervical and endometrial small cell carcinoma requires a differential curettage and immunohistochemical demonstration of neuroendocrine differentiation in order to arrive at the final diagnosis.

Biomarkers, Tumor↗

ALK-positive anaplastic large cell lymphoma with primary bone involvement in children.

We describe the clinical, radiologic, and pathologic features of primary bone anaplastic large cell lymphoma (ALCL) in 3 boys. Radiologic imaging showed lytic lesions involving sacrum, femur, or rib. Bone was the only site of disease in 2 cases; an associated partial lymph node was involved in case 3. Differential diagnoses included osteomyelitis and small round cell tumors of childhood, particularly Ewing sarcoma. Preoperatively, ALCL was not a diagnostic consideration in any case. Two cases showed classic large pleomorphic cells; 1 showed a composite pattern with a distinct small cell component and the more typical large cell type. Neoplastic cells in all cases showed strong CD30 and anaplastic lymphoma kinase expression with relatively weak epithelial membrane antigen positivity. Cytotoxic granule protein was expressed in 2 cases. All cases showed unusually strong expression of neuron-specific enolase (NSE). Two patients were disease-free at last follow-up (15 months and 11 years); 1 patient died of disseminated disease within a year of diagnosis. ALCL should be considered a diagnostic possibility when evaluating neoplastic bone lesions in children. Although expression of NSE in ALCL has not been emphasized in the literature, it is worth noting because it may pose a diagnostic pitfall.

Adolescent↗

Peripheral primitive neuroectodermal tumor after radiotherapy.

A 41-year-old man had a peripheral neuroectodermal tumor develop at the distal third of the fibula 4 years after radiotherapy for relapsed villonodular synovitis. This type of sarcoma usually is classified into the heterogeneic group of small round-cell bone tumors as a subdivision of Ewing's sarcomas. The immuno-staining positivity of the neoplastic cells for the neuron-specific enolase allowed the authors to make the diagnosis of a tumor with neuroectodermal origin. When the histologic study confirmed the diagnosis, the patient was treated with chemotherapy, surgical excision of the tumor, and adjuvant radiotherapy. Radiotherapy is thought to be involved in the genesis of osteogenic sarcomas as it has been shown in several reports, but there is no evidence in the literature of a peripheral neuroectodermal tumor developing after radiotherapy.

Adult↗

Ultrastructure of the Ewing's sarcoma family of tumors.

Specimens of 47 tumors diagnosed by routine light microscopy as Ewing's sarcoma of bone, and 5 similar soft tissue tumors (extraskeletal Ewing's sarcomas), were examined by transmission electron microscopy. Immunohistochemical stains were performed on all the tumors, and pre-therapy and post-therapy specimens from 5 of the patients were compared. Cell and nuclear areas were assessed in 41 cases by cytomorphometry by using low-magnification electron micrographs. DNA ploidy was determined by static cytometry on 51 of the tumors. None of the methods revealed differences between the bone and soft tissue tumors. The ultrastructural spectrum extended imperceptibly from the typical forms to markedly irregular variants, and was much broader than could be anticipated from the light microscopy. Neural features were observed but they were not common. Comparison of the Ewing's sarcomas with a group of other small round cell tumors (rhabdomyosarcoma, neuroblastoma, small cell carcinoma) using the same techniques showed that they have similar cell and nuclear areas despite the obvious differences in their immunophenotypes and ultrastructure. The collective findings are in keeping with the currently favored view that Ewing's sarcoma and peripheral primitive neuro-ectodermal tumor are the extremes in a morphologic continuum within which neural differentiation ranges from absent to prominent.

Biomarkers, Tumor↗