A ressonância magnética nas neoplasias de tecido adiposo, fibroso e muscular / MRI of lipomatous, fibrous and muscular tissues tumors

O elevado poder de resoluçäo de contraste entre partes moles faz da ressonância magnética (RM) o método diagnóstico de eleiçäo para o estudo dos processos neoplásicos dos tecido moles. Com o intuito de avaliar o papel efetivo da RM nesse campo, foram revistos 230 exames de 195 pacientes portadores de neoplasias de tecido adiposo, fibroso e muscular, examinados no Serviço de Ressonância Magnética do Instituto Nazionale dei Tumore de Miläo, com magneto operando a 1,5 tesla (T). A RM obteve eficácia global de 94,8 p/cento, com valor um pouco inferior (94,1 p/cento) para as recidivas. Os valores de sensibilidade variaram de 97,5 p/cento, para a apresentaçäo da patologia, a 96 p/cento, para as recidivas. A sensibilidade global foi de 96,3 p/cento. Registrou-se especificidade de 86,8 p/cento nos casos de reestadiamento. As características morfológicas e de sinal permitiram diferenciar as formas malignas e benígnas do tecido fibroso, graças ao comportamento característico das patologias dessa natureza quando avaliadas pela RM

Avaliaçäo radiológica dos tecidos moles da parede torácica em crianças eutróficas e desnutridas, na faixa etária de 0 a 2 anos / Radiologic evaluation of soft tissues of the thoracic wall in eutrophic and undernourished children aged 0-2

Analisaram-se os tecidos moles da parede torácia em telerradiografias de 101 ciranças eutróficas e desnutridas na faixa etária de 0 a 2 anos. Foi demonstrada a relaçäo existente entre o agravamento do estado nutricional e a reduçäo na espessura desses tecidos, a qual foi mais severa em faixa etária de 0 a 12 meses e nas crianças desnutridas de terceiro grau

In situ distribution of the beta-subunit of platelet-derived growth factor receptor in nonneoplastic tissue and in soft tissue tumors.

The distribution of the beta-subunit of platelet-derived growth factor receptor (PDGFR-beta) was assessed by a sensitive immunoalkaline phosphatase technique using the monoclonal antibody PR7212. Frozen tissue sections of several nonneoplastic human tissues were stained along with 42 soft tissue sarcomas, 16 benign soft tissue proliferations, and 7 epithelial tumors. In all nonneoplastic tissue, there was intense labeling of cell processes of perivascular fibroblasts or pericytes in and about the walls of muscular blood vessels and of fibroblast cell processes around some glandular and ductal epithelia. No PDGFR-beta was found in the endothelial cells of muscular arteries and veins, but cells of uncertain identity within some capillaries were immunoreactive and the possibility that endothelial cells of some small capillaries express PDGFR-beta could not be excluded. In kidney there was strong labeling of glomerular mesangial cells and interstitial fibroblasts. Some histological types of soft tissue sarcomas were uniformly and strongly labeled with anti-PDGFR-beta, but other types were infrequently labeled or unreactive. The order of decreasing frequency and strength of labeling of the various types of benign and malignant soft tissue proliferations was as follows: benign fibromatosis and neurofibroma greater than malignant fibrous histiocytoma greater than liposarcoma greater than leiomyosarcoma greater than rhabdomyosarcoma. No tumor cell labeling was detected in epithelioid, synovial or clear cell sarcomas, leiomyomas, or carcinomas, but there was usually strong labeling of fibroblast and/or pericyte cell processes within tumor, especially around blood vessels. We conclude that PDGFR-beta is strongly expressed by vascular and stromal tissues of most tumors and normal organs and by tumor cells of several types of soft tissue tumors and proliferations, most notably those of fibroblastic origin.

Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood.

Increased expression of P-glycoprotein is associated with multidrug resistance (MDR) in many cell lines. Significant levels of P-glycoprotein have been detected in a number of human tumors. The purpose of this study was to determine whether P-glycoprotein expression correlates with both response to chemotherapy and prognosis in soft tissue sarcoma of childhood. In a retrospective study, biopsy samples from 30 cases of rhabdomyosarcoma (RMS) and undifferentiated sarcoma (US) treated at The Hospital for Sick Children in Toronto were analyzed using a semiquantitative immunohistochemical procedure. P-glycoprotein was detected in nine patients, four at diagnosis, and five at subsequent biopsy. All nine patients relapsed after a clinical response (complete [CR] 55%, partial [PR] 45%) to chemotherapy. Twenty of 21 patients with consistently P-glycoprotein-negative tumors received chemotherapy and they all responded clinically (CR 80%, PR 20%). Only one of these 20 patients has relapsed. The probability of relapse-free survival was significantly different (P less than .000000012) in chemotherapy-treated patients whose tumors contained detectable levels of P-glycoprotein (n = 9), compared with those whose tumors contained no detectable P-glycoprotein (n = 20). The overall probability of survival was also significantly different in these two groups (P less than .0000267). Both relapse-free and overall survivals remained statistically different in the two groups of patients when analyzed by the log-rank method, after adjustment for differences in stages and sites. The incidence of other adverse prognostic factors in the two groups, for example, younger and older ages, low pretreatment lymphocyte counts, large tumors, and unfavorable histology were not significantly different. Thus, detectable P-glycoprotein appears to be an important adverse prognostic factor in children with soft tissue sarcoma, and consistent absence of the protein is associated with a favorable prognosis.

Alveolar soft part sarcoma. A clinicopathologic and immunohistochemical study of 12 cases.

Twelve cases of alveolar soft part sarcoma (ASPS) were reviewed. Seven of them arose primarily in the lower extremities, three in the head and neck region, and two in other parts. ASPSs in the head and neck region occurred in children before 10 years of age, whereas ASPSs in the other regions occurred in rather older patients. Moreover, ASPSs of the head and neck were relatively small in size, and were diagnosed earlier than those in other regions. Histologically, six cases (including all the head and neck cases) contained considerable area of small and indistinct alveolar structures. Four cases showed remarkable cellular pleomorphism. Immunohistochemical demonstration of vimentin, desmin, the beta-subunit of enolase and the MM isozyme of creatine kinase, together with the absence of immunoreactive cytokeratin, supported the myogenic nature of this rare tumor. A small number of S-100 protein-positive tumor cells were also observed. Follow-up data for these cases disclosed that the tumors containing considerable area of small alveoli and uniform small tumor cells formed distant metastases at an early stage.

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Masson's vegetant intravascular hemangioendothelioma. Fine needle aspiration cytology, histology and immunohistochemistry of a case.

Masson's vegetant hemangioendothelioma is a benign intravascular tumor, sometimes confused with such malignant vascular tumors as angiosarcoma, whose clinical appearance is nonspecific and whose diagnosis can only be established through microscopic examination. The fine needle aspiration (FNA) cytologic findings together with the histologic and immunohistochemical findings of such a tumor in a 22-year-old man are presented. Cytologically, the material obtained by FNA consisted of two distinct populations of cells. One type of cell had large nuclei (sometimes displaced towards the periphery), finely granular chromatin, prominent nucleoli and abundant globular cytoplasm. The second type of cell had spindle-shaped or oval nuclei, granular chromatin and scanty eosinophilic cytoplasm. Although these findings may permit the cytologic recognition of this entity, the aspirate in this case was interpreted as showing a vascular mesenchymal tumor of probable malignancy. Histologic examination of the excised tumor, aided by immunoperoxidase studies for factor VIII antigen that revealed the endothelial nature of the proliferating cells, established the correct diagnosis.

Cytoskeletal properties of alveolar soft part sarcoma.

The immunohistochemical expression of cytoskeletal proteins in alveolar soft part sarcoma (ASPS) was studied by light and electron microscopy. Of the five cases examined by the avidinbiotin-peroxidase complex method, variable numbers of immunoreactive cells for desmin were found in three, for vimentin in two, for muscle-specific actins in three, and for alpha-smooth muscle actin in four. Immunoelectron microscopic study demonstrated that desmin and vimentin were localized on whorled bundles of intermediate filaments in the perinuclear cytoplasm. In addition, a few dispersed intermediate filaments became evident in specimens treated with saponin and fixed with tannic acid. These immunohistochemical results indicate that a few tumor cells of ASPS may express some properties of the cytoskeleton of smooth muscle cells in addition to those of skeletal muscle cells. Considering the discrepancies reported in the actin isoforms demonstrated in myogenic tumors, we conclude that ASPS is probably a peculiar, primitive myogenic tumor that does not show any distinctive features of rhabdomyogenic or leiomyogenic differentiation.

Origin and relationship between different cell types in malignant fibrous histiocytoma.

The derivation of histiocyte-like cells in malignant fibrous histiocytoma (MFH) has been a matter of debate. To shed light on this problem two cell lines from two subsequent recurrencies of MFH were established. The existence of two different cell populations, mainly fibroblast-like in the first cell line and mainly histiocyte-like in the second, was shown by light and electron microscopy, DNA measurements, and karyotype analysis. By detailed banding analysis and identification of several identical chromosomal marker types in the two cell lines, it was proven that they originally derived from the same single cell or single clone. Because the first cell line, with mainly fibroblast-like cells, was in the hypotriploid region and the second, with mainly histiocyte-like cells, was in the penta-hexaploid region, the data explained the appearance of histiocyte-like cells in MFH as a consequence of chromosomal progression.

Ossifying fibromyxoid tumor of soft parts. A clinicopathological analysis of 59 cases.

We describe 59 cases of a microscopically unique neoplasm that has not been previously reported. The tumor almost exclusively affected adults (range 14-79 years) and had a male predominance (38 men and 21 women). It presented in most cases as a small, painless, well-circumscribed mass (median, 4 cm) in subcutis or muscle. It occurred chiefly in the upper and lower extremities (40 cases) and less frequently in the trunk (11 cases) and the head and neck region (eight cases). Microscopically, the tumor was partly lobulated and composed of small, round cells that had vesicular nuclei and indistinct cytoplasm. Typically, the cells were arranged in a cord- or nestlike pattern within a myxoid matrix that frequently showed transitions toward hyaline fibrosis and focal osteoid formation. In about two-thirds of the cases, the cells contained immunoreactive S-100 protein. An additional typical feature, seen in 48 (81%) of the 59 cases, was the presence of an incomplete shell of mature bone in the capsular region of the tumor. Follow-up information, available in 41 cases, revealed that 11 patients (27%) experienced one or more recurrences. One patient with three recurrences developed a second tumor in the opposite thigh, presumably a metastasis. None of the patients died of the tumor, but three died of causes unrelated to the disease. Although the histogenesis is uncertain, cartilaginous or neural origin seem to be most likely. Until this issue is resolved, we prefer the descriptive and less committal designation of "ossifying fibromyxoid tumor of soft parts."

Myofibromatosis in adults (adult counterpart of infantile myofibromatosis).

Five solitary, benign, soft-tissue tumors histologically resembling infantile myofibromatosis but which occurred in adults were found among more than 5,000 benign soft-tissue tumors from a tumor registry. The tumors clinically presented as superficial, painless, and slowly enlarging nodules, usually of more than 10 years' duration, that occurred in the upper (two cases) and lower (two cases) extremities or the buccal mucosa (one case). They developed in the dermis and subcutis as well-circumscribed nodules with an average diameter of 1.2 cm. They were composed of discrete and confluent fibrous tissue with a mixture of bundles of smooth muscle-like cells and a hemangiopericytoma-like area of immature mesenchymal cells. Immunostaining for actin and intermediate filaments revealed the myofibroblastic nature of the tumor cells. The tumors were surgically excised, and there has been no recurrence. Clinicians and pathologists should note that the lesion of infantile myofibromatosis can and does occur in adults.

[Clear cell sarcoma: a clinicopathological study of 11 cases].

The clinicopathologic, ultrastructural and immunohistochemical features of eleven cases of clear cell sarcoma are described. There were 6 males and 5 females with an average age of thirty-six (10-59 years). Tumors were found arising from the tendons, aponeuroses and fascial structures with a predilection for the lower and upper extremities. Follow-up data was available in 8 patients. Five of them are alive. Nevertheless, 3 of the five showed evidence of recurrence or metastasis. The other 3 patients died of tumor with metastasis. Microscopically, the tumors were composed of short fascicles of fusiform cells with a clear to eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli. Melanin was demonstrated in 5 cases and S-100 was known present focally in all cases, but no positive keratin staining was obtained. Electron microscopic studies revealed cell attachments and mature melanosomes. The exact histogenesis remains obscure, but our ultrastructural and immunohistochemical findings support the idea of neural crest origin of this tumor.

DNA cytometry of soft tissue tumours with TV image-analysis system.

We examined 69 soft tissue tumours for DNA content. Altogether 42 aspiration cytology and 27 imprint Feulgen-stained smears, each verified by histology, were analysed and the results evaluated with Böckings's algorithm. Except one false negative case (extramedullary ependymoma) 43 malignant and 25 benign soft tissue tumours could clearly be separated on the basis of their DNA content. The sensitivity of the positive cases (suspicious and malignant) came up to 97.7% with a false negative ratio of 2.2% while the sensitivity of the negative cases (benign) proved to be 75% with a 0% false positivity ratio. Cytometry is a useful aid in aspiration cytology diagnostics of soft tissue tumours particularly when their benign or malignant character is to be determined because the primary surgical therapy and consequently the further fate of patient, too, depend on the precise cytological diagnosis.

Therapeutic oophorectomy in metastatic breast cancer.

One hundred five patients undergoing therapeutic oophorectomy for metastatic breast cancer (n = 105) from 1975 to 1985 were reviewed. There were 54 responders (51%) to oophorectomy, with a median duration of response of 16 months (range, 3 to 129 months). Thirty of 42 (71%) estrogen receptor (ER)-positive patients responded to oophorectomy versus five of 24 (21%) ER-negative patients (P less than 0.001). Of the 39 patients with unknown ER status, 19 (49%) responded to oophorectomy. Osseous, soft tissue, and pulmonary metastases responded at similar rates. Of the 16 patients who had received adjuvant chemotherapy, there were five responders (31%) to oophorectomy. Second-line endocrine therapy was effective in 29 of 53 (55%) patients. Fifteen of 28 (54%) ER-positive patients responded to second-line endocrine therapy while two of six (33%) ER-negative patients responded. Twenty-three of 37 (62%) oophorectomy responders responded to second-line endocrine therapy versus six of 16 (38) nonresponders. Oophorectomy appears to be a valuable palliative treatment for metastatic breast cancer. ER-positive patients have the best chance of responding to this therapy. However, ER-negative patients have a reduced but definite chance of responding with a good duration of response. Response to further endocrine treatments is predicted by response to oophorectomy and to a lesser degree by ER status.

Immunocytochemical and ultrastructural studies of the histogenesis of Ewing's sarcoma and putatively related tumors.

The histogenesis of Ewing's sarcoma (EW) and extraskeletal Ewing's sarcoma (EEW) is still disputable. Their relationship to the so-called Askin's tumor, neuroectodermal tumor of bone, and peripheral neuroblastoma remains to be established. In an attempt to clarify these points, immunocytochemical and ultrastructural studies were done on tissues from 14 cases of EW, 4 cases of EEW, and 9 cases of primitive neuroectodermal tumor (PNET) and compared with neuroblastoma and olfactory neuroblastoma. Six tumors categorized initially as EW and EEW on biopsy, turned out to be PNET by extensive histologic and/or ultrastructural observations. Abundant glycogen was recognized not only in 16 of 18 cases of EW and EEW, but also in seven of nine cases of PNET. Fine fibrillar cell processes were seen between tumor cells, at least in limited areas even in cases of EW and EEW. Immunocytochemically, neuron-specific enolase (NSE), neuroblastoma cell surface antigen (NBCA), neuron cell surface antigen (NCSA), and neurofilament (NF) were demonstrated not only in neuroblastoma, but also frequently in cases of EW, EEW, and PNET. The results seem to suggest that EW and EEW represent the most immature forms of neuroectodermal tumor. Electron microscopic study showed predominantly primitive cells with occasional areas of cell processes, neurosecretory granules, and microtubules, suggesting a neuroectodermal origin.

Prognostic significance of Ki-67 reactivity in soft tissue sarcomas.

Proliferative activity of soft tissue sarcomas (STS) in 34 cases was estimated by immunohistochemical procedures (avidin-biotin complex [ABC] method) with monoclonal antibody Ki-67 which reacts with a nuclear antigen expressed in all phases of cell cycle except G0. In 20 of 34 cases (59%), varying numbers of Ki-67-positive tumor cells were detected with a range from 5 to 382 per 10 high power fields (HPF) (mean 57.2/10 HPF). Ki-67 index (the number of Ki-67-positive tumor cells/10 HPF) positively correlated with mitotic count (r = 0.428, P less than 0.02), cellularity (r = 0.447, P less than 0.01), and histologic grade (r = 0.473, P less than 0.01). The Ki-67 low index group (less than 50/10 HPF) showed more favorable prognosis than the high index group (more than 50/10 HPF) (P less than 0.005). Three cases with low mitotic count and unfavorable prognosis were proved to be the Ki-67 high index group (142-382/10 HPF). These results indicated that reactivity of tumor cells for Ki-67 is a useful prognostic marker in the patients with STS, and might be used as one of the histologic factors for the grading of STS.

Primary mucosal malignant melanoma: an immunohistochemical study of 12 cases with comparison to cutaneous and metastatic melanomas.

Immunohistochemical analysis of 40 formalin-fixed, paraffin-embedded malignant melanomas (12 primary mucosal, 16 primary cutaneous, and 12 metastatic cutaneous) was performed to study the possible differences in immunostaining profiles according to location. The majority of melanomas were reactive with a polyclonal antibody to S100 protein (P-S100; 85%), a monoclonal melanoma-specific antibody (HMB-45; 88%), and a monoclonal antibody to vimentin (90%), and there were no differences in staining profiles for these antibodies by anatomic location. In contrast, while 13 of 16 cutaneous melanomas (81%) and ten of 12 metastatic melanomas (83%) were reactive with a monoclonal antibody to S100 protein (MoAb-079), only five of 12 mucosal tumors (42%) showed positive staining for MoAb-079. Similarly, 14 cutaneous melanomas (88%) and 11 metastatic melanomas (92%) showed positive staining for neuron specific enolase (NSE), while only four mucosal melanomas (33%) were NSE-positive. Of the 40 melanomas, all but two were reactive with either P-S100, MoAb-079, or HMB-45. These findings suggest that MoAb-079 and NSE may be less sensitive markers than P-S100 and HMB-45 for routinely processed mucosal melanomas as compared with cutaneous and metastatic tumors.

Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis.

According to the autocrine hypothesis of cell growth, tumors, in contrast to normal tissue, might simultaneously express both a growth factor and its receptor, resulting in autoregulation and autostimulation of growth. In a related hypothesis, expression of either a growth factor or receptor might allow a tumor to escape exogenous controls on growth, and thereby correlate with malignant potential. Using immunohistochemistry, we investigated these hypotheses in 69 human soft tissue tumors (STT) by assaying for the expression of nerve growth factor and receptor, epidermal growth factor and receptor and platelet-derived growth factor. Both benign (B) and malignant (M) STT expressed a variety of factors and receptors. However, the frequency of any growth factor expression (90% M versus 55% B, p = 0.002) and of multiple factors (59% M versus 24% B, p = 0.006) was significantly greater in malignant tumors. Similarly, expression of any growth factor receptor (73% M versus 31% B, p = 0.001) and of multiple receptors (35% M versus 3% B, p = 0.002) was significantly more frequent in malignant STT. In terms of the autocrine hypothesis, growth factor/receptor co-expression was significantly more common in malignant STT (63% M versus 17% B, p = 0.0002). We conclude that (a) expression of both single and multiple growth factors and receptors was significantly more frequent in malignant STT; (b) support for an autocrine growth mechanism through simultaneous factor/receptor co-expression can be found in both benign and malignant STT; (c) co-expression, however, was more frequent in the malignant tumors; and (d) overall, growth factor and receptor expression, as well as co-expression, was related to biologic potential among human soft tissue tumors.

[Protein S-100 in spontaneous soft tissue and peripheral nerve neoplasms in rats]. / Belok S-100 v spontannykh opukholiakh miagkikh tkanei i perifericheskikh nervov krys.

16 spontaneous tumors of the peripheral nerves and 18 spontaneous tumors of mesenchymal origin in BDVI rats were studied by peroxidase-antiperoxidase method using anti-serum (DAKOPATT) against protein S-100. The majority of spontaneous peripheral nerve tumors were of cystic histological structure identical to that of cystic neurinomas induced in rats by ethylnitrosourea and almost all of these tumors were S-100 protein positive. The incidence of spontaneous neurinomas in BDVI rats was in some experiments as high as 5%. All tumors of mesenchymal origin (except one lipoma) were S-100 protein negative: 2 fibromas, 6 fibrosarcomas, 3 malignant fibrous histiocytomas, one rhabdomyosarcoma and one hemangioendothelioma. S-100 protein is found, as in human pathology, useful for distinguishing tumors of schwann cell and mesenchymal origin in rats.