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PubMed1995

Localized gastric non-Hodgkin's lymphoma of high-grade malignancy in patients with pre-existing chronic lymphocytic leukemia or immunocytoma.

Analyses for clonality in cases of Richter's syndrome have provided evidence for a clonal evolution of high-grade lymphoma in most patients, while in others an independent cellular clone seems to exist in the secondary neoplasm. Richter's syndrome with an isolated high-grade lymphoma of the stomach has been rarely reported in patients with pre-existing B cell chronic lymphocytic leukemia (CLL). We investigated four cases of CLL or lymphoplasmacytoid immunocytoma (LPIC) with development of a localized high-grade B cell lymphoma in the stomach. Southern blotting showed different rearrangements of the immunoglobulin light and heavy chain genes in the tumor cells of the low-grade lymphoma and the gastric tumor in two cases. Comparison of the DNA sequences of the CDR3 region of the immunoglobulin genes revealed different clones in another case. By means of chromosomal in situ hybridization, trisomy 3 was detected in two cases of high-grade lymphoma of the stomach, but not in the cells of the associated low-grade tumor. Our findings indicate that high-grade non-Hodgkin's lymphomas arising localized in the stomach of patients with CLL or immunocytoma are not clonally related to the pre-existing low-grade lymphoma and, therefore indeed, present true secondary neoplasms.

Aged↗

PubMed1994

The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading.

An analysis of 244 immature teratomas (IT) was undertaken to evaluate the clinical usefulness and reproducibility of the grading system. Clinical follow-up was available for 143 stage I tumors and ranged from 7 to 204 months (mean 85 months, median 84). Sixteen of 91 (18%) patients with high-grade teratomas were dead with metastases. These results are much improved over the years before the use of modern (1970 or later) combination chemotherapy. In contrast, only 3 of 52 (6%) patients with grade 1 tumors died, 1 of whom was living with tumor 6 years after surgery. None of the three neoplasms was adequately sampled. Of the three grade 1 tumors that progressed, the smallest one weighed > 1,500 g and the other two were huge; yet, only one to five slides per tumor were available for review. The study confirmed that small foci (2 mm or less) of other germ cell elements do not adversely affect the prognosis of IT. The reproducibility between pathologists of the traditional grading system for IT, based on the amount of immature neuroepithelium, is only moderate if a three-tiered scale is used and limited by the results of the least skilled observer (kappa = 0.54). Although never approaching complete agreement, interobserver variability is reduced if a two-tiered system is used (kappa = 0.66). Microscopic patterns that were the source of disagreement were identified. Agreement could be improved with training sessions.

Adolescent↗

PubMed2004

A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: implications for the histopathological assessment of paraffin-embedded specimens.

We have investigated whether immunohistochemical markers can identify differences in cell cycle phase distribution in ovarian serous neoplasms, including borderline tumours of different grades. Sections of normal ovary (n=18), serous cystadenoma (n=21), borderline serous tumours (n=21) and serous cystadenocarcinoma (n=15) were analysed by immunohistochemistry using markers of cell cycle entry (Mcm-2) and cell cycle phase, including cyclin D1 (mid-to-late G1), cyclin A (S phase), cyclin B1 (G2 phase) and phosphohistone H3 (mitosis). Double-labelling confocal microscopy confirmed marker phase specificity and phase estimations were corroborated by flow cytometry. On progression from normal ovary through serous cystadenoma and borderline tumours to cystadenocarcinomas, expression of Mcm-2 (P<0.0001), cyclin D1 (P=0.002), cyclin A (P<0.0001), cyclin B1 (P<0.0001) and phosphohistone H3 (P<0.0001) increased, paralleled by an increase in the S-phase fraction (cyclin A : Mcm-2 ratio; P=0.002). Borderline tumours of increasing grade also showed increased Mcm-2 and cyclin A expression, together with an increase in the S-phase fraction. Immunohistochemistry can be used to estimate cell cycle phase distribution in ovarian serous neoplasms, giving results similar to flow cytometric analysis and enabling direct assessment of tumour heterogeneity. Immunohistochemical estimates of the S-phase fraction may identify serous borderline tumours likely to exhibit malignant progression and/or select serous cystadenocarcinomas likely to respond to adjuvant therapy.

Biomarkers, Tumor↗

PubMed2006

Stromal differences in salivary gland tumors of a common histopathogenesis but with different biological behavior: a study with picrosirius red and polarizing microscopy.

Salivary gland neoplasms - pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma - share a common histogenetic trait, but differ markedly in their biological properties. The objective of the study was to assess the polarization colors of picrosirius red-stained stromal collagen fibers in these salivary gland neoplasms to evaluate their possible role in the histopathogenesis of the tumors and to evaluate the potential usefulness of this approach as a diagnostic tool. Ten cases of each tumor type and 10 cases of mucous extravasation phenomenon (control) were examined using picrosirius red staining and polarizing microscopy. In each case, at least 50 thin ( approximately 0.8 microm) and 50 thick (1.6-2.4 microm) collagen fibers were counted and classified as green-yellow or yellow-orange, the mean percentage was calculated and statistical differences analyzed by one-way ANOVA. Results showed a similar thin fiber distribution in all tumor types and controls (82-88% green-yellow, 12-18% yellow-orange, p>0.05). Thick fibers showed a different distribution in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (approximately 50% green-yellow) compared to pleomorphic adenoma and mucous extravasation phenomenon (approximately 13% green-yellow) (p=0.001). Thick fiber distribution was similar in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma (p>0.05). We conclude that with picrosirius red staining and polarizing microscopy, stromal collagen fibers differ significantly in pleomorphic adenoma from those in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma, but not from mucous extravasation phenomenon. Similarity between polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma may indicate that these tumor types represent a single entity with a broad spectrum of biological behavior.

Adenocarcinoma↗

PubMed2004

Vascular tumors of the skin: a selective review.

Cutaneous vascular proliferations are a vast and complex spectrum. Many appear as hamartomas in infancy; others are acquired neoplasms. Some vascular proliferations are hyperplastic in nature, although they mimic hemangiomas, i.e., neoplasms. The vast majority of the vascular lesions are hemangiomas. Between the hemangiomas and frankly angiosarcomas, there is a group of neoplasms that are angiosarcomas, albeit ones of low grade histologically and, probably, biologically. The term "hemangioendothelioma" has been created to encompass these neoplasms. Vascular proliferations are, fundamentally, composed of endothelial cells. Some hemangiomas, however, contain also abundant pericytic, smooth muscle, or interstitial components, or a combination of them. These heterogeneous cellular components are present usually in hemangiomas. Some of the newly described vascular proliferations, however, are difficult to differentiate from some of the angiosarcomas. Others are markers, occasionally, of serious conditions such as Fabry's Disease (angiokeratoma) and POEM's syndrome (glomeruloid hemangioma). Kaposi's sarcoma continues to be an enigma. The demonstration of Herpes virus 8 in this condition raises doubt about its neoplastic nature. The demonstration of endothelial differentiation of its nodular lesions is tenuous and its true nature remains unresolved. While physicians have known about post-mastectomy angiosarcomas from the origin of the radical mastectomy, a new group of unusual vascular proliferations of the mammary skin are being defined. These lesions arise in the setting of breast-conserving surgical treatment with adjuvant radiation therapy. The incubation period is usually 3 to 5 years, in contrast with the 10, or more, in classical cases of post-mastectomy angiosarcoma. These lesions usually are subtle, both clinically and histologically, in contrast with the "classical," dramatic presentation of mammary angiosarcoma. The spectrum of findings ranges from "simple" lymphangiectasia-like vascular proliferations to unequivocal angiosarcomas. The pathogenesis of these lesions remains a mystery. There are very few clues that allow one to separate hemangiomas from angiosarcomas. The presence of heterologous cellular elements and, particularly, well-developed smooth muscle components tends to favor a hemangioma. Similarly, the presence of thrombosis usually supports hemangioma. Nevertheless, there are no unequivocal or reliable individual diagnostic criteria. A thorough knowledge of the different conditions and their differential diagnoses eventually leads to the proper diagnosis in most cases.

Diagnosis, Differential↗

PubMed2005

Mucoepidermoid carcinoma of the skin: a distinct entity from adenosquamous carcinoma: a case study with a review of the literature.

Mucoepidermoid carcinoma (MEC) of the skin is an exceedingly rare but distinctive neoplasm with respect to its histopathologic features. It is similar if not identical in most respects to MEC of the salivary gland, a neoplasm whose prognosis is correlated with the pathologic grade. We report a case of MEC of the skin in a 79-year-old white woman who presented with an axillary mass. Beneath an unremarkable epidermis, a circumscribed, cystic neoplasm, unattached to the surface, was characterized by the presence of vague lobules of low-grade-appearing squamous cells accompanied by mucigenic and clear cells. A mucin stain highlighted the mucigenic cells and immunohistochemistry revealed pan-cytokeratin, cytokeratin 7, polyclonal carcinoembryonic antigen, and epithelial membrane antigen positivity. The cytokeratin 20 and gross cystic disease fluid protein were nonreactive. Inconsistency was encountered in the literature where some confusion existed as to whether MEC is synonymous with adenosquamous carcinoma of the skin. Elsewhere in the body, the latter tumor type is a squamous and gland-forming neoplasm with intermediate- to high-grade features rather than a tumor with mucigenic cells intermingled among intermediate and squamous cells. As in the case of MEC and adenosquamous carcinoma elsewhere in extracutaneous sites, we would propose that a pathologic distinction should be made in the skin for the sake of consistency and for prognostic purposes. Additionally, the immunophenotype of our case is similar to at least two other cases of cutaneous MEC, as well as MEC of the salivary gland, to support the hypothesis that this neoplasm is adnexal rather than epidermal in origin.

Aged↗

PubMed1989

Positron emission tomography in the detection of malignant degeneration of low-grade gliomas.

The management of low-grade gliomas represents a challenge to the physician as a significant proportion may undergo malignant degeneration to a high-grade tumor. We present the positron emission tomography (PET) scans, using [18F] fluorodeoxyglucose (FDG), of 12 patients who have histological and/or clinical evidence of malignant degeneration of a low-grade glioma. Each scan displays a focal area of hypermetabolism similar to that of malignant gliomas which arise de novo. Three patients also underwent PET scanning prior to malignant degeneration. When the initial scan is compared with the postmalignant degeneration study, a difference in tumoral glucose uptake can be recognized. A region previously shown to be hypometabolic develops focal hypermetabolism as malignant changes evolve. This study displays the utility of FDG-PET in the evaluation of malignant degeneration of low-grade gliomas. The knowledge that a neoplasm has altered its biological behavior may influence subsequent therapeutic options. If these findings can be confirmed in larger series and by other investigators, it is possible that FDG-PET may be adopted as one of the diagnostic tools for guiding the management of low-grade gliomas.

Adult↗

PubMed1996

Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma.

Round cell liposarcoma, a high-grade sarcoma, is a poorly differentiated form of myxoid liposarcoma, which is low grade. It is not known, however, how much of a round cell component within an otherwise typical myxoid liposarcoma results in a neoplasm that behaves as a high-grade sarcoma. Twenty-nine cases of myxoid liposarcoma of the extremities with or without a component of round cell liposarcoma were studied to semiquantitate the amount of round cell component needed to adversely affect prognosis. An estimate of the percent of necrosis, round cell liposarcoma, myxoid liposarcoma, and transitional areas was obtained for each slide on all cases. Transitional areas were defined as those that displayed an increased cellularity compared with typical myxoid liposarcoma, but in which the cells remained spindled, did not have overlapping nuclear borders, and retained an easily discernible plexiform vascular pattern. The amount of necrosis was subtracted from the total material available for evaluation, and a composite estimate of the percent of round cell, myxoid, and transitional areas was obtained. Two tumors were located on the upper extremity, 27 on the lower extremity; tumor size ranged frm 3 to 30 cm (median, 14 cm). All 29 tumors had a myxoid component, with a range from 12 to 100% (median, 73%). The range of transitional component for all 29 tumors was 0 to 88% (median, 11%). Twenty-one tumors had transitional areas (range, 4-88%). The range of round cell component for all 29 tumors was 0 to 58% (median, 0%). Twelve tumors had round cell areas (range, 1-58%). Seventeen patients are either alive without disease, or died from unrelated causes at 24-202 months (median, 96 months). Twelve patients are either alive with metastases or died of disease at 10 to 180 months (median, 53 months). Patients with > 5% round cell component in their initial tumor had a statistically significant higher rate of metastasis or death due to disease than those with < or = 5% round cell liposarcoma (p = 0.05). In addition, patients with myxoid liposarcoma with transitional areas did not fare worse than those with myxoid liposarcoma alone. In conclusion, we found that a round cell component of > 5% portends a higher risk of metastasis or death from disease. Furthermore, transitional areas alone do not appear to alter the prognosis of myxoid liposarcoma. Thus, only those areas that are unequivocally round cell liposarcoma should be designated as high grade.

Adolescent↗

PubMed1976

Malignant mixed germ cell tumors of the ovary. A clinical and pathologic analysis of 30 cases.

The clinical and pathologic features of 30 ovarian mixed germ cell tumors (neoplasms containing combinations of malignant germ cell elements) were studied to determine their behavior and to compare them with pure forms of malignant germ cell tumors. Dysgerminoma was the most common constituent, found in 24 (80%), followed by endodermal sinus tumor in 21 (70%), teratoma in 16 (53%), choriocarcinoma in 6 (20%), and embryonal carcinoma in 5 (16%). The actuarial survival for the entire group was 46%, and for patients with Stage I tumors it was 50%. The most important factors in predicting the prognosis for patients with Stage I disease was the size and the histologic composition of the neoplasm. If more than one-third of a Stage I neoplasm was composed of endodermal sinus tumor, choriocarcinoma, or Grade 3 teratoma, the prognosis was poor, whereas if the tumor contained less than one-third of these components or contained combinations of dysgerminoma, embryonal carcinoma, or Grade 1 or 2 teratoma, the prognosis was excellent. All patients whose neoplasm was less than 10 cm in maximum diameter survived, regardless of the composition of the tumor. Positive pregnancy tests in nonpregnant patients reflected the presence of either frank choriocarcinoma or scattered syncytiotrophoblastic giant cells. The latter did not appear to alter the prognosis. The finding of elevated serum levels of human chorionic gonadotropin (hCG) in 38% of the nonpregnant patients suggested that serial serum assays for hCG might be useful in staging and monitoring the response to treatment in these patients.

Adolescent↗

PubMed1995

Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material.

PURPOSE: To determine if the degree of enhancement of pulmonary nodules is directly related to the likelihood of malignancy and to the vascularity of the nodule. MATERIALS AND METHODS: Uncalcified 6-40-mm-diameter pulmonary nodules were studied in 163 patients with malignant neoplasm (n = 111), granuloma (n = 43), and benign neoplasm (n = 9). Serial thin-section computed tomography (CT) was performed before and after injection of 100 mL of nonionic contrast material at 2 mL/sec. The maximum level of enhancement was recorded. Eighteen histologic specimens were graded after vascular staining. RESULTS: Malignant neoplasms enhanced (median, 40.0 HU; range, 20-108 HU) significantly more than granulomas and benign neoplasms (median, 12.0 HU; range, -4 to 58 HU) (P < .001). With 20 HU as the threshold for a positive test, sensitivity was 100%; specificity, 76.9%; positive predictive value, 90.2%; negative predictive value, 100%; and accuracy, 92.6% (prevalence of malignancy, 68.1%). Degree of enhancement was significantly related to amount of central vascular staining (P = .003). CONCLUSION: Enhancement is an indicator of malignancy and vascularity.

Adult↗

PubMed1991

Malignant mesenchymoma. Clinicopathologic analysis of a series with evidence of low-grade behaviour.

Malignant mesenchymoma is a rare soft tissue neoplasm which, by definition, shows at least two distinct types of frankly malignant mesenchymal differentiation in addition to any "undifferentiated" or "fibrosarcomatous" areas. It is generally regarded as a high-grade tumor. A series of nine new cases is presented in which all patients except one were adults. Four tumors arose in the retroperitoneum, three in the thigh. The only definable constituents were rhabdomyosarcoma (eight cases), liposarcoma (seven cases), and osteo/chondrosarcoma (five cases). On histologic grounds, at least one element in each case would normally be regarded as high grade. Of six cases with a median follow-up of 4.2 years, only one has died from tumor. One further case was an incidental postmortem finding. In contrast to most current opinion, these data suggest that malignant mesenchymoma is not as aggressive as the histology would imply.

Adult↗

PubMed2004

Primary malignant mixed mullerian tumor of the vagina immunohistochemically confirmed.

CASE REPORT: We report the case of a 74-year old woman who presented with an ulcerated mass of the vagina. Histology of the tumor showed malignant mixed mullerian tumor (MMMT) with squamous and spindle cell stromal components, associated with high-grade vaginal intraepithelial neoplasia (VaIN 3). Immunohistochemical study of the neoplasm revealed that the malignant stromal tumor was a high-grade leiomyosarcoma. Despite the multimodal therapeutic approach, the patient died within 11 months. CONCLUSION: The vagina is a rare site of presentation of primary MMMTs and the present case is the second one immunohistochemically confirmed.

Aged↗

PubMed2001

Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis.

Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the approximately 6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas.

Astrocytoma↗

PubMed2000

Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors.

OBJECTIVE: Few molecular targets are both consistently and selectively expressed in a majority of central nervous system (CNS) neoplasms. Receptor tyrosine kinases have been implicated in brain tumor oncogenesis. We previously isolated one such receptor, discoidin domain receptor-1 (DDR1), from high-grade pediatric brain tumors. Here, we analyze the cellular origin and distribution of DDR1 expression in human brain tumors and its expression in tumor cells relative to surrounding brain. METHODS: By use of a digoxigenin-labeled DDR1 riboprobe, we investigated the expression of DDR1 messenger ribonucleic acid in a prospective series of 30 resected human primary and metastatic brain neoplasms, nonneoplastic human brain, and mouse embryonic brain, as well as a mouse glioblastoma model, by in situ hybridization. RESULTS: All the high-grade primary brain and metastatic brain tumors showed unequivocal, intense DDR1 expression within the majority of tumor cells, whereas expression was not observed in hyperplastic tumor blood vessels, normal brain blood vessels, inflammatory cells, or in the normal brain tissue that surrounded the tumor. Receptor expression was limited to tumor cells located within solid tumor tissue. Overall, 27 of 29 resected CNS tumors exhibited tumor cell-specific DDR1 expression, whereas one specimen composed of isolated glioblastoma cells within invaded brain parenchyma showed no detectable staining for this receptor. DDR1 was also expressed preferentially in the ventricular zone (a region of highly proliferating precursor cells) of mice at embryonic Day 15.5. CONCLUSION: We found that DDR1 is consistently expressed in all high-grade brain neoplasms studied and is selective for tumor cells in the specimens analyzed. The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS.

Adolescent↗

PubMed1999

[Expression and significance of basic fibroblast growth factor in ovarian epithelial neoplasm].

OBJECTIVE: To determine the effect of basic fibroblast growth factor (bFGF) on the biological behaviour of ovarian epithelial neoplasm. METHODS: Ten cases of normal ovarian tissues and eighty cases of ovarian epithelial tumor tissues were detected by immunohistochemical methods. Mias-2000 Picture Analysis System was used to study the relationship of bFGF expression intensity and microvessel count, FIGO stage, pathological grade and classification of ovarian epithelial neoplasm. RESULTS: 1. Expression of bFGF was mainly in cytoplasm and nucleus in several cells of borderline and malignant tumor. 2. The expression intensity of bFGF was closely related to the malignant degree of ovarian epithelial neoplasm. The density of bFGF expression was (3.35 +/- 3.52)% in normal ovarian epithelium, (19.25 +/- 21.73)% in benign tumor, (33.78 +/- 10.86)% in borderline tumor and (48.18 +/- 12.93)% in malignant tumor. The results indicated that bFGF might play an important role in carcinogenesis of ovarian epithelial neoplasm. 3. The expression intensity of bFGF was increased with the FIGO stage of ovarian tumor. 4. The expression intensity of bFGF was increased accompanying with the decrease of differentiation degree in ovian neoplasm. 5. In borderline tumor, expression intensity of bFGF in serous cystadenoma was significantly higher than in mucinous cystadenoma, which indicated bFGF might be an important factor in canceration of ovarian epithelial neoplasm. CONCLUSION: bFGF may play important roles in carcinogenesis, development, invasion and metastasis of ovarian epithelial neoplasm.

Cystadenoma, Mucinous↗

PubMed1998

KI67 proliferation index in tumors of the upper urinary tract as related to established prognostic factors and long-term survival.

OBJECTIVE: Nephroureterectomy is the standard treatment for tumors of the renal pelvis and ureter. Conservative management or indication of adjuvant treatment in these neoplasms is based mainly in histological grade and stage. The aim of this study is to assess the relation of Ki67 index with other established prognostic factors and to define its predictive value for long term survival, which could be useful in selecting the best treatment for each individual case. METHODS: 81 patients with urothelial tumors of the renal pelvis and ureter, diagnosed and treated between 1975 and 1993, comprised the present study. Ki67 immunostaining was performed in paraffin-embedded tissue. A cut-off limit of 20% was chosen. Tumor location, histological grade, histological pattern, local (T), nodal (N), vascular and perineural invasion and stage (TNM) were assessed in relation to the proliferation index and as prognostic criteria for survival in both univariate and multivariate analysis. RESULTS: The Ki67 proliferation index was found to be related to grade (p < 0.001), T (T0 vs T1-4; p < 0.01), N (p < 0.038), TNM categories (stage 0 vs I-IV; p < 0.048) and perineural invasion (p < 0.01). There was a marginal relation to vascular invasion (p < 0.11). Survival was better for the patients with low proliferating tumors (90%) than for high proliferating ones (67%) (p < 0.02). In the multivariate analysis only T stage was statistically significant (p < 0.01) but a highly suggestive trend was found for the Ki67 index (p < 0.07). CONCLUSIONS: Tumor proliferation assessed by Ki67 immunostaining is related to the progression of the disease and proved to be of predictive value for long-term survival in tumors of the renal pelvis and ureter. The Ki67 index is able to detect high-risk patients that could not be cured by radical surgery alone, raising the need for some type of aduvant treatment in these cases. The treatment predictive effect observed in low grade-low stage cases suggests its possible utility in patients managed conservatively.

Adult↗

PubMed1987

Synaptophysin expressed in the bronchopulmonary tract: neuroendocrine cells, neuroepithelial bodies, and neuroendocrine neoplasms.

Synaptophysin is an integral membrane glycoprotein with an Mr of 38,000 that occurs in the small, clear vesicles present in neuronal cells and tumors as well as in pancreatic islet cells and various neuroendocrine (NE) carcinomas. We found that synaptophysin is also expressed in normal NE cells of the lungs of newborn rabbits and mice as well as of human fetuses. In bronchial ganglion cells and in nerves, synaptophysin is coexpressed with neurofilament proteins (NFPs), whereas in solitary NE cells and in at least some of the neuroepithelial bodies (NEBs) of the bronchial mucosal lining, synaptophysin coexists with cytokeratins. We also studied a series of NE neoplasms of the lung covering the entire spectrum of differentiation (i.e., from carcinoids to small-cell NE carcinomas), and found that synpatophysin was present in the majority of them. In these tumors, synaptophysin was invariably coexpressed with cytokeratin filaments and desmoplakin, as well as, occasionally, with NFP. Synaptophysin was identified throughout, the whole range of these NE neoplasms, i.e., from benign to low-grade to aggressive and rapidly metastasizing carcinomas; its presence was unaffected by the highly variable expression of serotonin and/or neuropeptides in these neoplasms, and was unrelated to the presence or absence of associated endocrine syndromes. Our findings indicate that synaptophysin occurs in the neural as well as in the epithelial components of the dispered NE system of the lung as well as in the majority of NE neoplasms of this organ, and that the expression of this protein is therefore independent of the cytoskeletal characteristics and other differentiation features of both normal and transformed NE cells of the lung. We emphasize the value of synaptophysin as an immunocytochemical marker of NE differentiation.

Animals↗

PubMed2001

Clear cell odontogenic carcinoma: a clinicopathologic and immunocytochemical study of 5 cases.

CONTEXT: Odontogenic tumor composed predominantly of clear cells is a rare neoplasm of the jaws that was initially designated as clear cell odontogenic tumor. Subsequent reports in the literature, however, all have indicated that this tumor exhibits an aggressive behavior characterized by infiltrative local growth, recurrence, or metastases. OBJECTIVE: To ascertain the clinicomorphologic features and biologic behavior of this tumor group, we present 5 additional cases using the term clear cell odontogenic carcinoma. DESIGN: Histologic and immunohistochemical examinations were performed on clear cell odontogenic carcinomas from 5 patients. Clinical and follow-up data were recorded, and the literature was reviewed. RESULTS: The patients were 1 man and 4 women with an average age of 42.4 years at diagnosis. Three tumors occurred in the mandible and the other 2 in the maxilla. Four of the 5 cases occurred in the anterior or premolar areas of the jaws, appearing as poorly marginated radiolucencies. All cases consisted of islands and sheets of large clear cells and small basaloid cells with scanty eosinophilic cytoplasm, which were separated by thin, mature, fibrous septae. The tumors were unencapsulated and showed aggressive infiltration of the surrounding muscle and perineural tissues. Most of the clear cells contained cytoplasmic glycogen. Immunocytochemically, the tumor cells were positive for pan-keratin, cytokeratin 19, and epithelial membrane antigen, but were negative for vimentin, S100 protein, desmin, smooth muscle actin, human melanoma antigen (HMB-45), and alpha(1)-antichymotrypsin. Follow-up data showed 4 of 5 patients to have multiple local recurrences, and 1 of these 4 had submandibular lymph node metastasis and a fatal outcome due to uncontrollable tumor growth. CONCLUSION: These results suggest that odontogenic clear cell neoplasms are at least low-grade malignancies and should be classified as carcinomas.

Adenocarcinoma, Clear Cell↗