OLFACTORY NEUROBLASTOMA (ESTHESIONEUROEPITHELIOMA).
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An autopsy case of a malignant granular cell tumor of the right sciatic nerve was reported. The surgically excised malignant granular cell tumor of a 43-year-old women showed a close relationship with the sciatic nerve, and postmortem examination disclosed extensive metastases. Electron microscopic observations of the material obtained at surgery revealed many diagnostic granules containing myelin figures, as well as basement membrane-like structures around some of the tumor cells. Electron microscopic acid phosphatase staining suggested that the granules could be of a lysosomal origin. Immunohistochemical investigation showed the presence of S-100 protein in the tumor cells, a finding which is believed to be specific for the nervous system. And, focally, the cytoplasmic processes accompanied by basement membrane mimicked Schwann cells. This evidence suggested the highly malignant nature of the malignant granular cell tumor of probable Schwann cell origin.
The diagnostic value of ploidy level was investigated in a series of 707 tumors (from 707 patients) of the central and peripheral nervous system. The series contained 91 nerve sheath tumors (NSTs), 222 meningiomas (MNGs), 37 primitive neuroectodermal tumors (PNETs), 293 glial tumors of the adult (ATTs), and 64 brain metastases (MTTs). The ploidy level of each tumor was obtained by means of its DNA histogram type (DHT), which was computed (digital cell image analysis) on Feulgen-stained nuclei from archival formalin-fixed paraffin-embedded materials. The data reveal that the measurement of the ploidy level showed a diagnostic value in some of these tumor cases. Indeed, the proportion of highly aneuploid cases significantly (p < 0.05-0.01) decreased according to the sequence PNETs (72%)-->MTTs (64%)-->ATTs (40%)-->NSTs (23%)-->MNGs (9%). Nevertheless, this significant diagnostic value in terms of a distinction between benignity and malignancy only appears when all the tumors are taken into consideration. Indeed, at the level of one individual patient, our study shows that, like traumatic neuromas, schwannomas, or classical meningiomas, completely benign tumors can exhibit a high aneuploidy level. In contrast, some tumors from histopathological groups like brain metastases or PNETs, which are known to be clinically aggressive, could be completely diploid.
Serially transplanted neurogenic tumors of experimental origin were explanted in vitro and analyzed by scanning electron microscopy. In explants of intracerebrally transplanted gliomas, small stellate cells with branching processes were observed; in transplanted tumors of the peripheral nervous system, slender bipolar cells as well as fibroblasts emerged. The stereoscopic features were compared with the picture of conventional light microscopy. The findings are consistent with the assumption of the glial derivation of CNS-tumors induced with neurotropic alkylating carcinogens. The peripheral tumors are composed of Schwann-cell like elements and fibroblasts. The significance of the results for the cytogenetic derivation of brain tumors are discussed.
Tumors of the central and peripheral nervous system were induced in rats with ethylnitrosourea. Many of these tumors were transplanted in syngeneic recipients, and several cell lines were derived from them. An antiserum raised against one such cell line in C3H mice defined two cell surface antigens in cytotoxicity tests. One, the common antigen, was present on rat brain and embryonic tissues and was present in large amounts on most tumors or cell lines from the nervous system. Fibroblastic cell lines had smaller amounts of this antigen, which also could be detected by immunofluorescence. The other, restricted antigen was not detected on normal or other, restricted antigen was not detected on normal or embryonic tissues. It was present on six tumors from the nervous system, on one glial cell line, and on a Schwann-cell line RN22. In addition, it was present on four out of eleven cloned cell lines isolated from rat tumors at the Salk Institute. Two of the positive clonal lines had been shown to have properties unique to neuronal cells. The restricted antigen was therefore expressed on the cell surface of some, but not all, glial, Schwann, and neuronal neoplastic cells.
Hematogenous metastases of carcinoma to dorsal root ganglia was found in 2 of approximately 500 consecutive autopsies in which a lumbar dorsal root ganglion was routinely examined microscopically. The primary tumors were poorly differentiated colonic adenocarcinoma and oat cell carcinoma of the lung, both with widespread hematogenous metastases which spared the central nervous system. No symptoms were detected clinically. In the same series of patients the sural nerve as well as the lumbar plexus were histologically sampled but no examples of distant endoneurial metastases were found. The vascular endothelium of dorsal root ganglia is fenestrated and, presumably as a consequence, provides no blood-ganglion barrier. This microvascular difference may account for the susceptibility of the ganglia to metastases when compared to nerve trunks which posses unfenestrated endothelium and blood-nerve barrier.
In a series of some 7,000 patients with tumors of the central nervous system, 208 patients (about 3%) had some form of a malignant lymphoma. Slightly less than half of these tumors were primary in the brain; the remainder had cranial involvement as part of a generalized process. The tumors consisted of Hodgkin's disease, lymphosarcomas, reticulosarcomas and plasmacytomas. The brain was involved in one of two ways: either as localized tumor masses resembling certain gliomas, or as diffusely invasive neoplasms resembling exudative cellular inflammatory processes. They had a peculiar predilection for the septum pellucidum but occurred also in the cerebral lobes, basal ganglia, brain stem and cerebellum. They all produced a fibrillary stroma of reticulin fibers and they spread along the perivascular spaces, in the cerebrospinal subarachnoid space, or intraventricularly on and beneath the ependymal lining. One type of lymphoma often fused into another - thus a single tumor often consisted of Hodgkin's sarcoma, lymphosarcoma and reticulosarcoma. In an addition series of 57 cases of spinal cord involvement by malignant lymphomas, there were no instances of a primary tumor; all patients had either primary lymphomas of the brain with secondary spread to the spinal subarchnoid space, or had spinal cord compression as a result of tumor in the vertebrae, the spinal epidural space, or the spinal dura. Hence the spinal cord involvement was a secondary manifestation of a lymphoma elsewhere. Peripheral nerve involvement by lymphomas resulted in destruction of myelin sheaths and axons by tumor cell infiltration and the neuropathy was always part of a generalized lymphomatosis.
To evaluate whether perineural invasion (PNI) is an important prognostic factor in patients with rectal cancer, we reviewed the records of 373 patients who underwent curative surgery. Thirty-seven patients (9.9%) were identified as having tumors with PNI. The incidence of PNI was significantly increased in lesions categorized as stage III by the International Union Against Cancer (UICC) system (20%). There was a significant difference in local recurrence between patients with stage III lesions with PNI and those with stage III lesions without PNI (p < 0.005). Also, patients with PNI of stage III lesions had a significantly lower 8-year survival rate (26.7%, p < 0.001). We conclude that PNI is an important factor influencing the prognosis of patients with stage III disease. PNI should be classified as a subgroup of the clinical stage.
A retrospective histologic study of 145 consecutive autopsy cases of systemic malignant lymphomas (including lymphatic leukemias) was performed. The classification followed the Kiel Classification (Gérard-Marchant et al., 1974). There was an overall secondary CNS involvement in 26.2% of the total or in 30.4% of the non-Hodgkin's lymphomas including ALL, with intracranial lesions in 21.4 and 26.1%, respectively, and spinal epidural spread in 5.5 (5.1%). Peripheral nerve involvement was seen in almost 40% of the examined cases. Ten further cases were isolated ("primary") intracranial lymphomas without evidence of extraneural deposits or systemic lymphatic disease. The CNS complications in non-Hodgkin's lymphomas were diffuse meningeal and/or perivascular infiltration with or without invasion of the nervous parenchyma, and did not differ from those in CNS leukemia. Isolated solid mass lesions in the brain were only present in 7% of the secondary CNS lymphomas, but were seen in all instances of "primary" cerebral lymphomas. The incidence of CNS complications was highest in lymphoblastic lymphomas including ALL (39%), CLL (31%), immunocytic lymphoma (29%), less frequent in immunoblastic (18.7%), and centrocytic lymphomas (16.6%). No intracranial lesion was observed in centroblastic-centrocytic and centroblastic lymphomas which only produced epidural spread. Bone marrow involvement was present in 92.8% of the cases with secondary CNS lesions, and in 83.2% of the epidural lymphomas. Leukemic conversion, present in 44% of the total (52% with ALL), was demonstrated in 83.3% of the cases with secondary brain lesions, but was hardly combined with epidural spread. The histologic pattern of CNS lesions in non-Hodgkin's lymphomas and their frequent association with leukemic conversion suggest the importance of hematogenous dissemination rather than of direct spread from bone marrow or local manifestation in multisystem disease. Isolated ("primary") lymphomas of the CNS which are morphologically identical with the extraneural lymphomas may represent a primary, often lethal manifestation of a multisystem disease with or without secondary generalization.
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Extracapsular spread of squamous cell carcinoma in cervical lymph nodes is associated with approximately 50% decrease in survival and a twofold increase in regional recurrence. This study examines the hypothesis that increased regional recurrence may be, in part, due to unrecognized microscopic perineural invasion of the nerve rootlets of the cervical plexus. Thirty patients with head and neck squamous cell carcinoma with clinically N+ necks undergoing radical neck dissection were prospectively studied. Neck dissection specimens were evaluated for extracapsular spread, and the cervical plexus rootlets were histologically examined for perineural invasion. The incidence of extracapsular spread was 83% (25 of 30 patients). Only one (4%) of 25 had involvement of the cervical plexus, and this patient had gross as well as microscopic cervical plexus invasion. Microscopic perineural spread of squamous cell carcinoma in the cervical plexus occurs infrequently when extracapsular spread is present. Routine histologic evaluation of cervical rootlets for margins is warranted only when gross tumor is in close proximity to the cervical plexus.
BACKGROUND AND OBJECTIVE: Since there is no satisfactory treatment modality for diffuse malignant mesothelioma of the chest, we assessed surgical tumor resection followed by intraoperative photodynamic therapy with mTHPC in a phase I study. STUDY DESIGN/MATERIALS AND METHODS: Since 1990, eight patients have undergone intraoperative photodynamic therapy with m-tetrahydroxyphenylchlorin (mTHPC-PDT) following thoracotomy and surgical tumor resection. RESULTS: mTHPC-PDT-mediated tumor necrosis was characterized by tumor infarction due to tumor vessel necrosis and thrombosis, and its extent depended on drug-light conditions; 650 nm light delivered at 0.1 W/cm2 for 10 J/cm2 48 h after iv administration of 0.3 mg mTHPC/kg resulted in a 10-mm-deep complete tumor necrosis. Skin photosensitivity was related to the drug dose applied and occurred up to 17 days after iv administration of 0.3 mg mTHPC/kg, mTHPC-PDT of brachial plexus infiltrated by mesothelioma resulted in pain relief without deterioration of nerve function. CONCLUSION: Tumor resection and intraoperative mTHPC-PDT of the chest cavity is feasible under clinical conditions and offers local tumor control of sites involved. However, distant tumor spread was not prevented by this combined treatment modality and optimization of mTHPC-PDT is warranted for further intraoperative application.
BACKGROUND: The detection of perineural invasion (PNI) in the diagnostic transrectal biopsy of the prostate is associated with a 93% frequency of extracapsular disease extension in patients treated by prostatectomy for adenocarcinoma of the prostate. Extracapsular extension is associated with an inferior outcome compared with that of patients who have organ-confined disease. This study examined the association of PNI and treatment failure in a consecutive series of patients treated with three-dimensional conformal radiation therapy (3DCRT) alone. METHODS: The authors report actuarial biochemical no evidence of disease (bNED) survival rates for 484 consecutive patients with clinically localized prostate carcinoma diagnosed by transrectal needle biopsy who completed 3DCRT alone between May 1989 and December 1994. The median follow-up time was 28 months (range, 2-75 months), and the median dose to the center of the prostate was 7368 centigray (cGy) (range, 6316-8074 cGy). Patients were subdivided into 2 groups according to pretreatment prostate specific antigen (PSA) levels (< 20 ng/mL vs. > or = 20 ng/mL). Pathology records were reviewed for the presence or absence of PNI. bNED failure was defined as a PSA level > or = 1.5 ng/mL and rising on 2 consecutive occasions. bNED survival rates were calculated using Kaplan-Meier methodology and comparisons of survival curves were accomplished using the log rank test. RESULTS: The 3-year bNED survival for all 484 patients was 77%. The presence of PNI predicted decreased bNED survival in all patients. This detrimental effect, however, was confined to patients with pretreatment PSA values < 20 ng/mL. The bNED survival rates for patients with pretreatment PSA < 20 ng/mL demonstrated a highly significant decrease if PNI was present versus when it was absent (65% vs. 88% at 3 years, 39% vs. 65% at 5 years; P = 0.0009 for overall curve comparison). For patients with pretreatment PSA < 20 ng/mL, multivariate analysis of prognostic variables demonstrated a significant association between bNED survival and PNI (P = 0.002), palpation stage (P = 0.02), and pretreatment PSA (P = 0.006). Gleason score, age, and dose were not independent predictors of bNED survival in this group of patients. CONCLUSIONS: To the authors' knowledge, this is the first report demonstrating that PNI detected on diagnostic transrectal biopsy is a significant predictor of decreased bNED survival in patients treated with radiotherapy. The subgroup of patients affected are those with pretreatment PSA < 20 ng/mL. This result suggests that such patients may benefit from more aggressive treatment, particularly the use of larger planning target volumes or adjuvant therapies.
The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also known as malignant epithelioid schwannoma, is a relatively rare and recently characterized clinicopathologic entity. The epithelioid variant of MPNST shares many clinical features with conventional MPNST but is characterized by different histologic and cytologic features. These include a distinctive nesting pattern and an abundance of cytoplasm not seen in histology of conventional nerve sheath tumors. Cytologically, the epitheliod variant shows a propensity to cellular discohesiveness and a plasmacytoid or epitheliod appearance that is in contradistinction to the spindled appearance of the usual MPNST. Herein, we report our experience with fine-needle aspiration (FNA) of two epithelioid malignant schwannomas and discuss the FNA cytologic differential diagnosis.
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