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PubMed2002

Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas.

BACKGROUND: Conventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management. METHODS: In the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow-up. RESULTS: The authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so-called "dedifferentiated" phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low-grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis. CONCLUSIONS: These data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low-grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms.

Biomarkers, Tumor↗

PubMed2003

C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma.

OBJECTIVE: Differentiating between adenoid cystic carcinomas (ACCs), polymorphous low-grade adenocarcinomas (PLGAs), and the monomorphic adenomas (including canalicular adenomas, trabecular adenomas, and basal cell adenomas) can present a diagnostic challenge, especially when examining tissue obtained from small incisional or fragmented biopsies. Recent studies have revealed that overexpression of the tyrosine kinase receptor protein c-kit occurs in a narrow subset of malignant neoplasms, including gastrointestinal stromal tumors, myeloid leukemias, seminomas, and ACCs. C-kit reportedly is not expressed in PLGAs. We compared the expression of the c-kit antigen in the malignant salivary gland neoplasms ACC and PLGA with its expression in salivary gland monomorphic adenoma (including canalicular adenoma and basal cell adenoma). STUDY DESIGN: Formalin-fixed paraffin-embedded sections of 49 salivary gland neoplasms (17 monomorphic adenomas, 17 PLGAs, and 15 ACCs) accessioned between 1989 and 2002 were retrieved from the files of the Department of Pathology, Long Island Jewish Medical Center, and were stained with an anti-c-kit polyclonal antibody. RESULTS: C-kit reactivity was uniformly positive in the cytoplasm of luminal neoplastic cells in ACCs (15/15, 100%). Positive reactivity was also identified in the majority of PLGAs (16/17, 94%), with at least 25% of the tumor cells being positive. Similar reactivity was seen in monomorphic adenomas (16/17, 94%). CONCLUSIONS: In contrast to previous reports, we find that c-kit expression was not restricted to ACC but was expressed in all 3 tumor types evaluated (ACC, PLGA, and monomorphic adenoma). Therefore, c-kit does not appear to be a useful marker for distinguishing between either ACC and PLGA in equivocal cases, or in benign and malignant salivary gland neoplasms.

Adenocarcinoma↗

PubMed1992

Ring chromosome in parosteal osteosarcoma. Clinical and diagnostic significance.

In this study, two specimens of a parosteal osteosarcoma, a rare primary bone neoplasm comprising only 3-6% of all osteosarcomas, were cytogenetically analyzed utilizing standard techniques. In contrast to the complex karyotypes previously reported in osteosarcoma, this particular histologic subtype was characterized by a single chromosomal aberration, a ring chromosome. Ring chromosomes have been described as characteristic for two other low-grade malignant mesenchymal neoplasms, well-differentiated liposarcoma and dermatofibrosarcoma protuberans. We propose that the observation of a ring chromosome in osteosarcoma also correlates with a low-grade malignant potential.

Adolescent↗

PubMed1999

Oxyphilic proliferations of the respiratory tract and paranasal sinuses.

Neoplasms of the upper respiratory comprised primarily of eosinophilic cells are, in general, rare, and they include a diverse group of lesions. Low-grade oncocytic neuroendocrine neoplasms (so-called oncocytic carcinoids) can be encountered in several locations throughout the respiratory tract. The oncocytoma and related entities, lesions that presumably arise from minor gland tissue, can likewise be seen from the nasal cavity to the lung; differences in clinical significance may relate to the location of such lesions, and are discussed herein. Granular cell tumor is another entity that can involve both the upper respiratory tract and lungs, and specific features of this lesion in different anatomic sites are highlighted. The oncocytic variant of Schneiderian papilloma is an important nasal lesion to recognize, because of important therapeutic and prognostic implications of that diagnosis. Finally, unique oncocytic variants of glomus tumor and pulmonary alveolar adenoma are discussed, as well as eosinophilic varieties of pulmonary carcinomas and mesotheliomas.

Adenoma↗

PubMed2002

"Revertant" mammary solid papillary carcinoma in lymph node metastasis.

A case of invasive carcinoma of mixed papillary and not otherwise specified ductal type with areas of solid papillary ductal carcinoma in situ(DCIS) is reported. The solid papillary areas were predominantly of low nuclear grade, but a small area of intermediate-grade solid papillary neoplasm was also seen within the tumor, together with an area suggestive of microinvasion. The massive regional nodal tumor load consisted of invasive papillary carcinoma and revertant low-grade solid papillary carcinoma with no myoepithelial cells around the circumscribed solid papillary areas. This is the first report of a solid papillary pattern simulating intraductal carcinoma in lymph nodes, and the first time that a solid papillary carcinoma is reported in association with invasive papillary carcinoma. The case suggests that mammary carcinomas with a solid papillary pattern may sometimes be of higher grade than usual, and do not always represent a DCIS, but may be invasive.

Aged↗

PubMed2000

Malignant gliomas.

Gliomas are a heterogeneous group of neoplasms that comprise the majority of tumors originating in the central nervous system (CNS). In adults, the most frequently encountered of these are high-grade or malignant neoplasms of astrocytic and oligodendrocytic lineage, ie, anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), and anaplastic oligodendroglioma (AO), respectively. Tumors of mixed lineage are also seen, the most common of which is designated anaplastic oligoastrocytoma (AOA). Standard treatment for these tumors is typically surgery, followed by radiation then chemotherapy. Surgery is required for a definitive histopathologic diagnosis, which in turn will dictate subsequent therapy options. Moreover, aggressive tumor resection improves survival outcomes, and in many cases, the patient's neurologic function. We generally advocate the safest, maximal resection attainable for patients with these tumors as a way to improve prognosis. In almost all cases, surgery is followed by radiation therapy. Postsurgical irradiation is the most effective treatment currently available for improving survival. There is also mounting evidence to suggest that additional radiation, given in the form of brachytherapy or radiosurgery, at initial diagnosis as a "boost" to standard radiation or at tumor recurrence, may provide added improvement in survival outcome. Radiosurgery and brachytherapy are therapies often used to treat eligible patients at this institution. Adjuvant chemotherapy, conventionally given after radiation, may offer a modest survival benefit in some patients with GBM. Bischloroethylnitrosourea (BCNU) is the typical first-line agent used, but chemotherapy seems to be most beneficial in young patients, with little if any impact on survival for patients over 60 years old. At this institution, we often defer treatment with adjuvant chemotherapy for elderly patients with GBM due to lack of efficacy and the attendant risk with chemotherapy. For anaplastic astrocytomas, oligodendrogliomas, and oligoastrocytomas, a commonly accepted standard is adjuvant chemotherapy following irradiation with the three-drug regimen--procarbazine, CCNU, and vincristine (PCV). This is due to an earlier clinical trial that showed a survival advantage in patients treated with adjuvant PCV compared with patients that received BCNU. However, recent data suggest that treatment with either PCV or BCNU may be appropriate. Both regimens now appear to have equal efficacy for anaplastic gliomas in light of a more recent analysis done with larger numbers of patients. AOs are a unique case with respect to tumor chemosensitivity and patient survival. Molecular studies have identified a subpopulation of patients with AO whose tumors have lost chromosomes 1p and 19q. Patients with this molecular pattern have an exceptional responsiveness to PCV chemotherapy and have prolonged survival. Currently, trials are being conducted to confirm this finding and to determine the best treatment regimen for these patients, with particular regard to the timing of radiation and chemotherapy.

Antineoplastic Agents↗

PubMed1978

Benign and low grade variants of mixed mesodermal tumor (adenosarcoma) of the ovary and adnexal region.

Eleven examples of a rare group of neoplasms composed of both epithelial and mesenchymal components are reported. Ten arose from the ovary and one arose separately in the para-ovarian region. The neoplasms are distinctive in that the stoma is more cellular than that of adenofibromas, but epithelial component is not malignant, as in carcinosarcoma and mixed mesodermal tumors, and the stoma is not sarcomatous in the low grade varieties. The 11 cases were highly variable in the cellularity and atypism of the stromal cells. The term, adenosarcoma, for these tumors is not acceptable because some were too low a grade to be regarded as sarcomas, and reports of the uterine counterpart disclose that some contain heterologous elements. For that reason, a term that will embrace the full spectrum of changes in the stroma--benign through sarcomatous--is needed. We propose that they be regarded as variants of mixed mesodermal tumor so that both the benign neoplasms and low grade sarcomas can be accommodated under one designation. Of the 11 cases, five lowest grade examples were all confined to the ovary and did not recur after surgical excision, but some of these were borderline in malignancy and probably would have progressed if untreated. Two of the 3 intermediate grade neoplasms extended beyond the ovary but were arrested by surgical excision. The 3 highest grade neoplasms were overly sarcomatous. One of these extended beyond the ovary but was arrested by combination chemotherapy. The para-ovarian adenosarcoma (also high grade) metastasized and proved fatal.

Adenofibroma↗

PubMed1993

Morphological appearance, growth kinetics and glial fibrillary acidic protein (GFAP) expression in primary in vitro explant culture of astrocytic neoplasms.

Astrocytomas of different grades of malignancy were cultured as primary explant and their sequential growth pattern, glial fibrillary acidic protein (GFAP) expression and labelling index (LI) using bromodeoxyuridine (BrdU) were assessed and correlated with the grade of malignancy of the original tumor tissue. Low-grade astrocytomas showed patterns of growth that diverged from anaplastic astrocytomas and glioblastoma multiforme. The GFAP expression decreased with increasing time in culture in all astrocytomas irrespective of the grading. Maximum GFAP was, however, expressed in the morphologically well-differentiated stellate cells. Contrary to expectations, lower BrdU LI was observed in glioblastoma multiforme in comparison to low-grade astrocytomas, which suggests some unidentified mechanism of differentiation in vitro for astrocytomas of higher grade of malignancy. Hence, in contrast to reported literature on the prognostic value of studies on primary cultures, the present study cautions the extrapolation of the in vitro findings for astrocytomas.

Adolescent↗

PubMed2004

Cribriform-Morular Variant of Papillary Carcinoma: Association with Familial Adenomatous Polyposis - Report of Three Cases and Review of Literature.

We describe a rare variant of papillary thyroid carcinoma (PTC), the Cribriform-Morular Variant (C-MV). A handful of cases have been described in the literature of this entity. They exhibit the morphologic features of a distinctive papillary neoplasm along with solid, cribriform, and squamoid-morular areas. The cribriform and morular features make this a separate entity which could be mistaken for a high grade aggressive thyroid neoplasm. These lesions are usually associated with familial adenomatosis polyposis (FAP) but rarely may be sporadic. We report three cases that we have encountered.

Journal Article↗

PubMedDate not supplied

Malignant primitive neuroepithelial tumour of soft tissues mimicking a cellular ependymoma.

A malignant small blue-cell soft tissue tumour in a 13 year-old girl is reported. By light microscopy the tumour showed prominent pseudo-rosettes suggesting peripheral neuroepithelial tumour (PNET) with ependymal differentiation or extraspinal cellular ependymoma. Ultrastructural and immunocytochemical findings helped in excluding an ependymal neoplasm (low-grade malignancy) and supported the diagnosis of malignant primitive PNET mimicking a cellular ependymoma (high-grade malignancy).

Adolescent↗

PubMed1985

The glycosaminoglycans of human bladder cancers of varying grade and stage.

The glycosaminoglycans of four normal human bladders and fourteen bladder cancers were characterized and quantitated (after proteolytic extraction) by specific enzyme digestion, cellulose acetate electrophoresis and densitometry. Hyaluronic acid, heparan sulfate, dermatan sulfate and chondroitin sulfate were identified in both normal and cancerous bladders. Hyaluronic acid and dermatan sulfate were the major glycosaminoglycans of the normal epithelium/submucosa while heparan sulfate and dermatan sulfate were predominant in normal bladder muscle. Bladder cancer glycosaminoglycan content was influenced by the stage and grade of the neoplasm. Hyaluronic acid and dermatan sulfate tended to decrease and chondroitin sulfate to increase in infiltrating cancers, whereas a decrease in the percentage of heparan sulfate correlated closely with higher grade tumors. The bladder cancer glycosaminoglycan profile may be indicative of the tumor's invasive potential.

Adult↗

PubMed1998

AgNORs in benign, borderline and transitional cell neoplasms of the urinary bladder.

Argyrophilic nucleolar organizer regions (AgNORs) were studied in 106 tissue samples from the urinary bladder (6 normal transitional epithelium, 5 cystitis, 12 hyperplastic, 14 dysplastic lesions, 12 carcinoma in situ, 4 transitional cell carcinoma grade 0, 12 grade I, 15 grade II and 12 grade III) to evaluate their role in differentiating benign, borderline and malignant lesions. The NOR counts presented a rising scale from normal (2.21), inflammatory (3.93 for both cystitis and hyperplasia), dysplastic (4.16), carcinoma in situ (5.08) to malignant lesions (5.28 grade I, 6.59 grade II and 8.37 grade III). It was concluded that AgNORs do not have a diagnostic role in these lesions, but that they can act as a reliable adjunct to existing parameters in the early detection of tumour recurrence and grading of malignant neoplasms.

Carcinoma in Situ↗

PubMed2003

Immunohistochemical expression of glucose transporter Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes.

All malignant cells appear to have increased needs for glucose in vitro as well as in vivo. The enhanced glucose uptake is mediated through transporters (Gluts), whose action and expression are regulated by oncogenes and growth factors. Cyclin D1 is a nuclear protein that plays an important role in regulating the cell cycle by promoting entry of cells from the G1 to S phase. Increased expression of Glut1 glucose transporter and cyclin D1 have been reported in several neoplasms. In the present study we examined the expression of Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes. We studied 78 infiltrating ductal carcinomas (25 grade 1, 36 grade 2, and 17 grade 3) with negative lymph nodes. Glut1 was expressed in 28% of grade 1, 63.8% of grade 2 and 58.7% of grade 3 carcinomas. Nuclear expression of cyclin D1 was detected in 32% of grade 1, 44.4% of grade 2, and 41.2% of grade 3 carcinomas. From our study it appears that in breast carcinomas with negative lymph nodes Glut1 expression is better correlated to the grade of the neoplasm than cyclin D1.

Biomarkers, Tumor↗

PubMedDate not supplied

Pathology consultation. Metastatic patterns of salivary gland neoplasms.

Long-term follow-up of salivary gland carcinomas allows a better evaluation of their biologic malignancy than the traditional five-year period. Metastases (distant and local) are possible over the entire lifetime of a patient and are dependent upon histologic grade, persistence of neoplasm and clinical stage. Distant metastases to bone and lungs are manifested by nearly every carcinoma. Metastases to regional lymph nodes vary according to histologic type and it appears that the adenoid cystic carcinoma has the lowest incidence of that event.

Carcinoma↗

PubMed2002

Monoclonal gammopathy after low-grade MALT lymphoma: evidence for a second neoplasm.

We report the case of a patient with lymphoma of the salivary gland, at first diagnosed as lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but later found to infiltrate the bone marrow. At diagnosis, the patient had a polyclonal increase of gamma-globulins. Five years after initial diagnosis, the patient presented with monoclonal gammopathy and infiltration of the bone marrow with neoplastic cells. Initially, the patient had received chemotherapy with different protocols (including etoposide, cyclophosphamide, fludarabin, methotrexate, and vincristine), none of which induced a lasting response. Therapy with rituximab (chimeric anti-CD20 monoclonal antibody) finally led to partial remission. Eighteen months after rituximab, progressive lymphoma in the abdomen and a monoclonal gammopathy developed. The bone marrow showed infiltration by lymphoplasmacytoid cells (monoclonal expression of the light-chain type lambda, positive for CD20, heterogeneous expression of CD45). The patient achieved another short clinical response with 4 cycles of the CHOP-protocol, but soon the lymphoma progressed again. Five years and 8 months after the initial diagnosis, the patient died from septicemia and progressive lymphoma. By polymerase chain reaction (PCR) for the IgH gene it was shown that lymphoma cells were initially oligoclonal in the salivary gland and, later, biclonal in the bone marrow. Sequencing of two bands of apparently same length showed that these manifestations of lymphoma were not identical. Taken together, our data show that the initial low-grade oligoclonal MALT lymphoma was no longer present and a more aggressive biclonal lymphoma with plasmacytoid differentiation had developed. The new lymphoma was clonally distinct and produced high amounts of monoclonal IgG lambda by immunoelectrophoresis. The relationship of the second lymphoma to the initial MALT lymphoma is discussed.

Antibodies, Monoclonal↗

PubMed2002

Endometrial stromal sarcoma of the retroperitoneum.

Endometrial stromal sarcoma (ESS) is an uncommon neoplasm whose occurrence outside the uterus is extremely rare in the absence of metastasis or extension of a primary uterine neoplasm. When ESS occurs in such locations it is often associated with the uterine adnexa or serosal surface of various organs. Although rare, ESS is usually considered in the differential diagnosis of spindle cell neoplasms in the female patient. We report a case of ESS arising in the retroperitoneum and discuss the morphologic and immunohistochemical features in the context of the differential diagnosis of a retroperitoneal low-grade spindle cell neoplasm occurring in the female patient.

Aged↗

PubMed2002

Interobserver discrepancy using the 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms: practical choices for patient care.

PURPOSE: Morphological classifications designed by experts to stratify neoplasms according to biological potential must define categories that are reproducible among practitioners or the schemes actually create the heterogeneous populations that they seek to avoid. The application of the 1998 World Health Organization/International Society of Urologic Pathology scheme for urothelial neoplasms was studied in a community practice setting. We documented interpretive discrepancies for each category of neoplasm and determined whether a period of pathologist education may have a positive effect on the frequency of discrepant interpretations. The results suggest that patients may benefit from modifying the classification system. MATERIALS AND METHODS: A consecutive series of specimens was divided into learning and study sets that were each independently examined by 3 pathologists. Specimens in the learning set were interpreted without previous structured education, while those in the study set were interpreted immediately after intensive education. Interpretations for each specimen were compared and interpretive discrepancies were analyzed. RESULTS: Case distribution after education was similar among the pathologists but interpretations for any particular specimen often differed. The level of interpretive discrepancies varied according to the morphological similarity among categories in the classification scheme and was not necessarily decreased by education. When pathologists were required to discriminate between papillary urothelial neoplasm of low malignant potential and low grade carcinoma, the discrepancies were 50% after education compared with 39% before education. In contrast, there were no discrepancies when the discrimination was between papillary urothelial neoplasm of low malignant potential and high grade carcinoma or carcinoma in situ. Eliminating categories with poor reproducibility markedly improved the likelihood of unanimous agreement among practitioners but a probably irreducible level of 10% discrepancies remained. CONCLUSIONS: The 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms requires certain discriminations that cannot be reliably made by practitioners. Modifying the scheme to create categories of low grade neoplasm and high grade carcinoma would markedly increase its practical value to patients without significantly altering patient care.

Carcinoma, Transitional Cell↗

PubMed1989

Cytologic composition of the untreated glioblastoma with implications for evaluation of needle biopsies.

To study the progression of astrocytic neoplasms and to provide practical information about the topography of the glioblastoma multiforme, the distribution of eight defined cell types was mapped from whole brain sections of 18 glioblastomas studied postmortem. Based on the densities and topographic distributions of well-differentiated and anaplastic cells, three principal categories of neoplasms were defined. In one group of three cases, multifocal glioblastomas appeared to be emerging in the background of a better differentiated, and presumably precursory, astrocytic neoplasm. In another group of nine cases, the neoplasms were more intimate mixtures of well and poorly differentiated cells. The third group of five cases was composed of neoplasms that were largely undifferentiated without a component of better differentiated cells. The study suggests that progression from a better differentiated neoplasm to one composed largely of undifferentiated cells is common in the fibrillary astrocytic neoplasms. Although some glioblastomas appear largely undifferentiated and consistent with the de novo appearance of overt malignancy, the size of these neoplasms and the patterns of necrosis leave open the possibility that a preexisting better differentiated neoplasm had been obliterated by necrosis and the overgrowth of the anaplastic component. The potential topographic variation of cellular constituency in a glioblastoma underscores the care that must be exercised in utilization of the needle biopsy technique in the diagnosis and grading of astrocytic neoplasms.

Biopsy, Needle↗