Roberto Falzoni

Sarcomas often express constitutive nitric oxide synthases (NOS) but infrequently inducible NOS

Nitric oxide (NO) has a dual action in tumors, with both pro-tumor and anti-tumor activities. NO is produced by nitric oxide synthases (NOS). There are three enzyme isoforms: two of them are constitutively produced (neuronal or brain NOS and endothelial NOS), and one is an inducible form (iNOS). NOS expression has been shown in several epithelial tumors, but there is no report addressing NOS expression in sarcomas. The authors evaluated the expression of NOS in 97 cases of various sarcomas spotted in duplicate in a tissue array paraffin block. Eighty-four of the 97 tumor specimens (86.6%) expressed nNOS, and most of them showed a strong expression of the isoenzyme. Only chondrosarcomas and liposarcomas had significant numbers of negative cases, and all pleomorphic sarcomas, alveolar soft part sarcomas, angiosarcomas, gastrointestinal stromal tumors, and synovial sarcomas showed some degree of positivity. Forty-three cases (44.4%) showed eNOS immunostaining, but only 15.5% showed a strong signal, with emphasis on angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcoma. Strong expression of iNOS was observed in only 9 cases (9.3%), with weak expression in another 26 cases (26.8%). Strong expression of iNOS was found in malignant peripheral nerve sheet tumors, liposarcomas, pleomorphic sarcomas, fibrosarcomas, chondrosarcomas, and synovial sarcomas. Apparently alveolar soft part sarcomas are unusual in their capacity of expression of NOS isoforms, and in a very peculiar pattern. In conclusion, sarcomas in general commonly express constitutive NOS, and only a few types of sarcomas can express iNOS, the isoenzymes capable of releasing large amounts of NO. More comprehensive studies should be performed to better understand the clinical importance of NOS expression and NO production in sarcomas.

Glial fibrillary acidic protein in tumor types with cartilaginous differentiation

Glial fibrillary acidic protein (GFAP) is a member of the intermediary filament protein family. It is an important component of astrocytes and a known diagnostic marker of glial differentiation. GFAP is expressed in other neural tumors and pleomorphic adenoma and, less frequently, in cartilage tumors, chordomas, and soft tissue myoepitheliomas. The aim of this study was to evaluate the role of GFAP and its reliability in nonglial tumors as an immunohistochemical marker. We evaluated GFAP gene and protein expression using Q-PCR and immunohistochemistry, respectively, in 81 and 387 cases of soft tissue, bone tumors, and salivary pleomorphic adenomas. Immunohistochemistry staining for GFAP was observed in all osteosarcomas (8 cases), all pleomorphic adenomas (7 cases), in 5 of 6 soft tissue myoepitheliomas, and in 21 of 76 chondrosarcomas. By Q-PCR, GFAP was highly expressed in pleomorphic adenomas and, to a lesser extent, chondrosarcomas, soft tissue myoepitheliomas, and chondroblastic osteosarcomas. The results that we obtained by immunohistochemistry and Q-PCR were well correlated. GFAP is a potential marker for tumors with cartilaginous differentiation, supported by evidence that GFAP is expressed in certain cases of myoepithelial tumors by immunohistochemistry, including soft tissue myoepitheliomas, which are related to cartilaginous differentiation. These findings contribute significantly to the diagnosis of soft tissue myoepitheliomas with cartilaginous differentiation and chondroblastic osteosarcoma in mesenchymal tumors.

Prognostication of Soft Tissue Sarcomas Based on Chromosome 17q Gene and Protein Status: Evaluation of TOP2A, HER-2/neu, and Survivin

BackgroundTopoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value.MethodsEighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray.ResultsTOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes.ConclusionsThese findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.

Management of desmoid-type fibromatosis involving peripheral nerves

Desmoid-type fibromatosis is an uncommon and aggressive neoplasia, associated with a high rate of recurrence. It is characterized by an infiltrative but benign fibroblastic proliferation occurring within the deep soft tissues. There is no consensus about the treatment of those tumors. We present a surgical series of four cases, involving the brachial plexus (two cases), the median nerve and the medial brachial cutaneous nerve. Except for the last case, they were submitted to multiple surgical procedures and showed repeated recurrences. The diagnosis, the different ways of treatment and the prognosis of these tumoral lesions are discussed. Our results support the indication of radical surgery followed by radiotherapy as probably one of the best ways to treat those controversial lesions.

Tracheal Malignant Melanoma: Successful Outcome With Tracheal Resection

Primary tracheal malignant melanomas are uncommon neoplasms: only five cases have been reported. Different therapeutic approaches are described, with a short life expectancy observed. We report a case of a young woman with a primary tracheal malignant melanoma who underwent complete tracheal resection and is free of disease 4 years after surgical treatment.

Prognostic significance of occult lymph node micrometastasis in gastric cancer: a histochemical and immunohistochemical study based on 1997 UICC TNM and 1998 JGCA classifications

BACKGROUND: Micrometastasis is a single or a cluster of malignant cells inside the lymph node that are not detected by routine histopathological sections. Micrometastasis is related to poorer prognosis in many gastric cancer studies the real significance of these cells is still controversial. AIM: To evaluate if lymph node micrometastasis is a significant independent prognostic factor and important risk factor for recurrence in gastric cancer. METHODS: A total of 1290 lymph nodes from 28 patients with gastric cancer, since 1998 until 2003, treated by radical resection (D2 and modified D3 lymphadenectomies) were studied. Three sections per lymph node were stained by Hematoxilin-Eosin, histochemical (AB-PAS) and immunohistochemical (AE1-AE3) techniques. Kaplan-Meiers survival curves and Log-rank/Cox tests were used in order to compares lymph node micrometastasis positivity, depth (pT) and location of tumor in gastric wall, histologic type, lymphatic, vascular and perineural invasion, lymph node status (pN) and stage. RESULTS: There were worse prognosis and recurrence in patients with positive lymph node micrometastasis related to vascular and perineural invasions, advanced lymph node status and advanced stages. CONCLUSION: Lymph node micrometastasis seems to be a significant independent prognostic factor and important risk factor for recurrence in gastric cancer, in a context of radical D2 lymphadenectomy

Edema pulmonar não cardiogênico após circulação extracorpórea

O edema pulmonar nao cardiogenico e uma complicacao grave, de conhecimento recente, que se segue a cirurgias cardiacas com circulacao extracorporea. O quadro clinico e de instalacao rapida, caracterizando-se, principalmente, por broncoespasmo, secrecao sero-hemorragica pelas vias aereas e hipotensao arterial. O diagnostico diferencial com insuficiencia ventricular esquerda e realizado pela constatacao de pressoes normais, ou baixas, em territorio pulmonar e atrio esquerdo, sugerindo mecanismo de aumento subito da permeabilidade capilar. Os autores relatam a ocorrencia desta sindrome em 6 pacientes submetidos a operacoes cardiacas com circulacao extracorporea, tecendo consideracoes sobre os mecanismos fisiopatologicos aventados, meios de diagnostico, terapeutica adotada, bem como os achados histopatologicos dos pacientes com ma evolucao.

Perineurioma of the posterior interosseous nerve: surgical treatment.

Intraneural perineurioma is a benign tumor that occurs in less than 1% of peripheral nerve tumors; no more than 90 cases have been reported1,2. Tumorous lesions of the posterior interosseous nerve (PIN) have rarely been described3–5. An 18-year-old woman presented with a longstanding his tory of spontaneous progressive weakness in the PIN dis tribution (Figure 1). Ultrasonography and MRI studies (Figure 2) showed a nodular lesion in the PIN, measuring 1.0 cm at its greatest diameter. At surgical exploration a tumor (Figure 3) involving all the nerve fascicles was entirely re sected. The nerve was repaired by termino-terminal neurorrhaphy. Figure 4 shows the histological examination.

Treatment of rectal leiomyoma by endoscopic resection

Leiomyomas of the rectum are rare, with low reported incidence in literature. In most cases, patients are asymptomatic, and are often incidental endoscopic findings. The difficult distinction from leiomyosarcomas, associated with the possibility of recurrence, implies the absence of a standard treatment. Endoscopic resection, if well indicated, may be a therapeutic option. In this study, we report two cases of asymptomatic leiomyoma of the rectum in two patients, discovered incidentally during a routine colonoscopy, removed by conventional polypectomy and discuss its diagnostic and therapeutic aspects based on a literature review.

Doença de Rosai-Dorfman cutânea: relato de caso e revisão de literatura

We report a patient with cutaneous Rosai-Dorfman disease that presented on the right buttock, a red brown plaque with yellowish areas and red-brown satellite papulas. The histopathologic exam revealed inflammatory infiltrate predominantly of lymphocytes and histiocytes with wide and clear cytoplasm containing intact inflammatory cells (emperipolesis). Any other alteration in the physical exam and laboratorial was not found. The Rosai-Dorfman disease is a rare form of histiocytic proliferation and the strictly cutaneous form is still rarer. The aetiology is unknown and the clinical and histologic correlation enables the correct diagnosis.