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PubMed2001

Oligodendroglial neoplasms: current concepts, misconceptions, and folklore.

Given current prognostic and therapeutic implications, the accurate classification and grading of oligodendroglial neoplasms has become critical. However, the prevalence of morphologically ambiguous gliomas, subjective histologic criteria, personal biases, oligodendroglioma mimics, and the lack of specific oligodendroglioma markers has led to high interobserver variability and created a contentious problem encountered daily in active surgical neuropathology practices. Since histologic assessment is still a powerful prognosticator, it appropriately remains the diagnostic gold standard. However, recent efforts have focused on identifying the most reproducible and clinically relevant criteria, standardizing classification and grading schemes, and searching for useful ancillary biologic and genetic markers capable of further stratifying an otherwise heterogeneous patient population. This paper reviews the morphologic and genetic spectrum of oligodendroglial neoplasms, recent diagnostic and prognostic developments, and potential future directions.

Biomarkers, Tumor↗
PubMed1984

A quantitative study of histiocytic reticulum cells in diffuse and follicular non-Hodgkin's lymphomas.

Histiocytic reticulum cells have been counted in 160 lymph nodes, comprising 50 high grade non-Hodgkin's lymphomas, 90 lymphomas of low grade histology, and 20 specimens exhibiting reactive follicular hyperplasia. The histiocytes were shown immunohistochemically by virtue of their content of the cysteine proteinase cathepsin B. A consistent and striking finding was that high grade lymphomas contain many more histiocytes than low grade lymphomas. Immunoblastic neoplasms contain up to 24.2% of these cells, whereas low grade diffuse lymphomas possess only up to 3.6% histiocytes. Histiocytic reticulum cells were also counted in benign or malignant follicular lesions in standard areas from follicle centres only. No significant differences were found between low grade lymphomas and hyperplastic nodes. These findings are discussed in relation to previous, more limited studies.

Cathepsin B↗
PubMed2001

Mucoepidermoid carcinoma of the oral cavity.

There is presently no uniformly accepted grading system for mucoepidermoid carcinoma, largely due to a lack of consensus as to what criteria should be used to formulate histological grades. The present study was undertaken to determine the relationship between histological grade, clinical stage and survival in these neoplasms. Clinical and histological data from 34 patients with mucoepidermoid carcinoma were reviewed. Mucoepidermoid carcinoma was most common in the parotid gland (44.1%), while 25% of patients had tumors in the minor salivary glands. Low, intermediate, and high-grade neoplasms accounted for 61.7%, 26.5%, and 11.8% of tumors, respectively. There was a general trend towards increasing clinical aggressiveness with increasing histological grade. Similarly, postoperative tumor recurrences were marginally more common in high-grade than in low-grade mucoepidermoid carcinomas. However, both of these findings were statistically insignificant, mainly due to small sample size, late clinical presentation, poor clinical follow-up, incomplete management and incomplete records. These factors explain the relatively low survival figures in the present study, as compared to higher survival figures in white patients with mucoepidermoid carcinoma.

Adolescent↗
PubMed1998

High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient.

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above that average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Adolescent↗
PubMed2005

Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis.

UNLABELLED: This study evaluated the potential usefulness of (11)C-choline PET/CT for detection and localization of tumors within the prostate. We used the results of step-section histopathologic examination as the standard of reference. METHODS: The results were analyzed on a sextant basis. We reviewed the results of the (11)C-choline PET/CT scans of 36 patients with prostate cancer and of 5 control subjects with bladder cancer. All patients underwent (11)C-choline PET/CT and, subsequently, radical prostatectomy with lymph node dissection within 1 mo. (11)C-Choline PET/CT scans were obtained 5-10 min after intravenous injection of 370-555 MBq of (11)C-choline. Images were reviewed visually and semiquantitatively using maximum SUV and tumor-to-background ratio. RESULTS: On a sextant basis, histopathologic analysis detected cancer foci in 143 of 216 sextants; high-grade prostate intraepithelial neoplasm foci were detected in 89 of 216 sextants (in 59 sextants in association with carcinoma, in 30 sextants alone), acute prostatitis was detected in 7 of 216 sextants (in 3 sextants in association with carcinoma, in 4 sextants alone), and 39 of 216 sextants were normal. PET/CT demonstrated focal (11)C-choline uptake in 108 sextants (94 of which involved tumor), and 108 sextants showed no abnormal (11)C-choline uptake (49 of which were false negative). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 66%, 81%, 71%, 87%, and 55%, respectively. In the 5 control subjects, high-grade prostate intraepithelial neoplasm was detected at histologic examination in 16 of 30 sextants. PET/CT showed increased (11)C-choline uptake in 5 of 16 sextants. CONCLUSION: This study demonstrated the feasibility of using (11)C-choline PET/CT to identify cancer foci within the prostate. However, we also found that (11)C-choline PET/CT has a relative high rate of false-negative results on a sextant basis and that prostatic disorders other than cancer may accumulate (11)C-choline. Therefore, our data do not support the routine use of PET/CT with (11)C-choline as a first-line screening procedure for prostate cancer in men at high risk.

Aged↗
PubMed1994

Cytogenetics as a tool in the histologic subclassification of chondrosarcomas.

Chondrosarcomas are a heterogeneous group of bone neoplasms of which the basic neoplastic tissue is cartilaginous. Frequently the histologic diagnosis and grading of chondrosarcomas is difficult and the histologic appearance does not always reflect the biologic behavior of these tumors. Therefore, it is important to find other parameters that can be of help in the proper diagnosing and grading of these neoplasms. To this end, we attempted to correlate the chromosomal pattern of chondrosarcomas to their histologic subtypes and grades. The cytogenetic analysis of two intermediate-grade chondrosarcomas of bone, and a review of the literature, are presented.

Bone Neoplasms↗
PubMed1995

High incidence of other neoplasms in patients with low-grade gastric MALT lymphoma.

BACKGROUND: Low-grade gastric MALT lymphoma is an uncommon tumour for which a close association with chronic Helicobacter pylori infection has been suggested. However, given the rarity of MALT lymphoma of the stomach despite the high prevalence of H. pylori infection, it seems plausible that genetic host factors might play a fundamental role in gastric lymphomagenesis. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 83 patients with low-grade gastric MALT, all of whom resided in a geographic area (southern Switzerland and northern Italy) where the incidence of gastric tumours appears to be uncommonly high. RESULTS: One or more additional cancers were observed in 17 of 83 patients (20%, 95% CI 12% to 31%) for a total of 23 tumours. Of these, 5 were diagnosed prior to, 12 concomitantly with, and 7 after the gastric MALT lymphoma. Eleven patients had a single additional solid tumour (13%, 95% CI 7% to 22%); 3 patients had non-Hodgkin's lymphoma and one had Hodgkin's disease. Multiple additional cancers were present in 3 cases. Nine of 83 patients have died and 8 of them of a second cancer. CONCLUSIONS: Unexpectedly an extraordinarily large number of patients with other malignancies was observed in this series. The reasons for this finding are still unknown, but genetic alterations are speculated to play an important role.

Female↗
PubMed2007

Pleuropulmonary involvement in pseudomyxoma peritonei: morphologic assessment and literature review.

Intrathoracic spread in patients with pseudomyxoma peritonei (PP) is rare. We reviewed 101 patients uniformly treated at our institution for PP of appendiceal origin. In that study, we suggested mucinous carcinoma peritonei (MCP) as the pathologic terminology for all cases of PP. Four patients had pathologically documented pleuropulmonary involvement. We subsequently examined another patient with pleural invasion. Of 5 patients, 3 had low-grade histologic features in the peritoneum; these showed variably proliferative, bland-appearing neoplastic cells arising from low-grade appendiceal mucinous neoplasms. In 2 cases, 1 or more pulmonary parenchymal metastases of low histologic grade developed. The lack of pleural involvement argued against transdiaphragmatic tumor extension. The third patient with low-grade MCP had direct extension through the left diaphragm involving the left pleural and pericardial spaces without pulmonary parenchymal involvement. In the 2 patients with high-grade MCP, right-sided pleural effusions developed. Neither patient had documented injury to the diaphragm. Pleural cytologic examination revealed high-grade adenocarcinoma cells singly, in small clusters, and in large spheres. The smear backgrounds contained wispy mucin. None of the 5 patients developed thoracic lymph nodal metastases. Although rare, mucinous neoplasms from PP may involve the thorax.

Adult↗
PubMed1997

Epithelial-myoepithelial carcinoma of the lung: immunohistochemical and ultrastructural observations and review of the literature.

Epithelial-myoepithelial carcinoma is a rare low-grade malignant salivary gland neoplasm that most commonly occurs in the parotid gland but can also arise in minor salivary glands. We report a case of a primary epithelial-myoepithelial carcinoma of the lung. The patient is a 55-year-old black woman who presented with increasing shortness of breath and productive cough of at least 3 months duration. A left lower lobe endobronchial lesion was identified radiographically. Surgical resection of the lesion was performed, obtaining a circumscribed, nonencapsulated 3.9 cm tan mass which was attached to the inner wall of the lateral basal segment bronchus. A biphasic proliferation of epithelial (cytokeratin positive; S-100 protein and muscle-specific actin negative) and myoepithelial (S-100 protein and muscle-specific actin positive with focal weak cytokeratin positive) cells was identified by immunohistochemical and ultrastructural analysis of formalin-fixed tissue. The patient is disease free 7 months after resection. Pulmonary epithelial-myoepithelial carcinoma likely derives from the submucosal bronchial glands and should be added to the growing list of salivary gland-type neoplasms that may occur as primary pulmonary neoplasms. Because its histology is identical to salivary epithelial-myoepithelial carcinoma, pulmonary epithelial-myoepithelial carcinoma should be considered a low-grade malignant neoplasm and should be designated as epithelial-myoepithelial carcinoma is preference to other terms that may not convey its malignant potential. Although follow-up on reported cases is limited, lobectomy with negative bronchial margin should be curative.

Carcinoma↗
PubMed2002

Differential expression between pilocytic and anaplastic astrocytomas: identification of apolipoprotein D as a marker for low-grade, non-infiltrating primary CNS neoplasms.

Fibrillary astrocytoma, the most common primary central nervous system neoplasm, is infiltrating, rapidly proliferating, and almost invariably fatal. This contrasts with the biologically distinct pilocytic astrocytoma, which is circumscribed, often cystic, slowly proliferating, and associated with a favorable long-term outcome. Diagnostic markers for distinguishing pilocytic astrocytomas from infiltrating anaplastic astrocytomas are currently not available. To identify genes that might either serve as markers or explain these distinct biologic behaviors, cDNA microarray analysis was used to compare the expression of 7,073 genes (nearly one quarter of the human genome) between these 2 types of astrocytoma. Messenger RNAs pooled from 3 pilocytic astrocytomas and from 4 infiltrating anaplastic astrocytomas were compared. Apolipoprotein D (apoD), which expressed 8.5-fold higher in pilocytic astrocytomas, showed the greatest level of differential expression and emerged as a potential marker for pilocytic tumors. By immunohistochemistry, 10 of 13 pilocytic astrocytomas stained positively for apoD, while none of 21 infiltrating astrocytomas showed similar staining. ApoD immunostaining was also seen in 9 of 14 of gangliogliomas, 4 of 5 subependymal giant cell astrocytomas (SEGAs), and a single pleomorphic xanthoastrocytomas (PXAs). By in situ hybridization, pilocytic astrocytomas, in contrast with infiltrating astrocytomas, showed widespread increased apoD expression. SAGE analysis using the NCBI database showed a higher level of expression of apoD RNA in pilocytic astrocytoma than in any of the other 94 neoplastic and non-neoplastic tissues in the database. ApoD is associated with decreased proliferation in some cell lines, and is the protein found in highest concentration in cyst fluid from benign cystic disease of the breast. ApoD might play a role in either decreased proliferation or cyst formation in pilocytic astrocytomas, gangliogliomas, SEGAs, and PXAs.

Apolipoproteins↗
PubMed1996

Papillary urothelial hyperplasia. A precursor to papillary neoplasms.

Precursor lesions of papillary urothelial neoplasms have not been well characterized. We reviewed the surgical pathology files of the Johns Hopkins Hospital and three regional hospitals from 1992 to present. Sixteen cases of papillary hyperplasia, defined as undulating urothelium arranged into thin mucosal papillary folds, were identified (in 11 men and five women: age range, 40-89 years). Relative to the diagnosis of papillary hyperplasia, nine patients had a history of papillary urothelial neoplasms; in one of these cases, the patient also had subsequent papillary urothelial neoplasms, and two of these patients had concurrent papillary urothelial neoplasms with papillary hyperplasia. In one of these nine cases, papillary hyperplasia arose in the scar of a prior papillary urothelial neoplasm. In two cases, the patients had concurrent, yet no prior history, of papillary urothelial neoplasms. Of these 11 cases, three had multiple resections showing papillary hyperplasia over time. In case 12, the patient had a history of moderate urothelial atypia. The remaining four patients had no history of papillary urothelial neoplasms or urothelial atypia. We describe papillary hyperplasia as a well-defined entity that is usually asymptomatic and generally found on routine follow-up cystoscopy for papillary urothelial neoplasms. Papillary hyperplasia appears to be a precursor lesion of low-grade papillary urothelial neoplasms.

Adult↗
PubMed1995

[Hematological neoplasm--how to treat low-grade lymphomas].

Low-grade lymphomas are rare in Japan, comprising about 10% of non-Hodgkin's lymphomas. They are indolent in natural history with median survival of 7-10 years. Despite a good initial response to radiotherapy or chemotherapy, most patients (Pts), being incurable, ultimately die of their disease. Pts with clinical stage (CS) I/II disease are generally treated with locoreginal radiotherapy. Long-term survival of 60% to 70% and disease-free survival (DFS) of 50% to 55% have been reported. The more precise the staging procedures, the better the results. Chemotherapy used as a primary therapy or as an adjuvant to radiotherapy may improve DFS of pts with CS II with many sites of lymph node involvement or bulky disease. For CS III/IV disease there is no accepted standard therapy. There is no survival advantage for any of the different first-line treatment methods ranging from initial deferral of treatment albeit in highly selected pts, an alkylating agent +/- steroid hormone, to combination chemotherapy (C-MOPP, CHOP, ProMace-MOPP etc) +/- irradiation. The international index for prognostication of aggressive lymphoma has also been shown to be applicable to stratification of low-grade lymphomas. In future studies effectiveness of treatment strategies should be investigated with long-term DFS and improved quality of life being set as primary endpoints.

Female↗
PubMed1990

Bladder cancer screening: lessons from a biologically based model of bladder cancer progression and therapeutic intervention.

The screening of asymptomatic high-risk populations has been evaluated using a biologically based model of bladder cancer. The model is built upon a mathematical representation of the induction of precursor bladder lesions with possible progression through clinical disease states. Screening strategies are based on regimens that include voided urine cytology. Diagnostic and therapeutic components of the model provide the basis for end results evaluation. Cytology screening is projected to increase average life expectancy by 1 to 3 years among those diagnosed while reducing deaths from bladder cancer by more than 50%. The additional contribution to be realized with a screening test of perfect sensitivity would be primarily in the increased identification of dysplasia and low-grade superficial papillary neoplasms, lesions that are much less life-threatening than the high-grade lesions already detectable by cytology. The theoretical potential of screening is not realizable because of diagnostic inaccuracies and treatment failures.

Adult↗
PubMed2004

Low-grade salivary duct carcinoma: description of 16 cases.

Low-grade salivary duct carcinoma is a rare neoplasm. We report on 16 patients, with a median age of 64 years. All but one tumor arose from the parotid gland, including one tumor that arose in an intraparotid lymph node; one arose in the submandibular gland. Tumors consist of single to multiple dominant cysts, accompanied by adjacent intraductal proliferation. Cysts are lined by small, multilayered, proliferating, bland ductal cells with finely dispersed chromatin and small nucleoli. Separate, smaller ductal structures are variably filled by proliferating ductal epithelium with cribriform, micropapillary, and solid areas. The overall appearance is very similar to breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Foci of definitive stromal invasion were seen in four tumors. Two tumors demonstrated transition from low- to intermediate- or high-grade cytology, with scattered mitotic figures and focal necrosis. S-100 revealed diffuse strong expression in all 9 cases studied. Myoepithelial markers (calponin) highlighted supportive myoepithelial cells rimming the cystic spaces, confirming the intraductal nature of most, or all, of six tumors studied. Nine tumors studied for Her2-neu antigen were uniformly negative. Follow-up was obtained on 13 of our 16 patients. All patients were disease-free after surgery 6 to 132 months (median 30 months). Low-grade salivary duct carcinoma is a low-grade neoplasm with an excellent prognosis; it may be treated by conservative but complete resection. Its resemblance to atypical breast ductal hyperplasia, or micropapillary/cribriform intraductal carcinoma, distinguishes it from high-grade salivary duct carcinoma, papillocystic acinic cell carcinoma, and cystadenocarcinoma.

Aged↗
PubMed2026

Novel genomic score predicts survival with immune checkpoint inhibition in neuroendocrine neoplasms.

BACKGROUND: Immune checkpoint inhibition (ICI) has activity in Grade 3 (G3) neuroendocrine neoplasms (NENs), but predictive biomarkers of long-term overall survival (OS) are currently lacking. METHODS: We derived a genomic scoring system using a retrospective cohort of 54 NEN patients treated with nivolumab and/or ipilimumab, alongside a chemotherapy-only control (n&#x2009;=&#x2009;15) and pan-cancer validation cohort (n&#x2009;=&#x2009;1661). An overall genomic score (GS-O) combining positive (GS-P) and negative response genes (GS-N) was calculated. RESULTS: In the ICI cohort, patients with GS-O&#x2009;&#x2265;&#x2009;2 had significantly better outcomes: median OS was not reached, compared to 3.9&#x2009;months for low scores (HR = 0.007, P&#x2009;<&#x2009;.001). After multivariate adjustment, GS-P was independently associated with improved OS while GS-N showed a trend towards worsened OS. Importantly, GS-O&#x2009;&#x2265;&#x2009;2 did not predict survival in the chemotherapy-alone cohort but was validated as independently predictive in the pan-cancer validation dataset (HR = 0.92, P&#x2009;<&#x2009;.001). CONCLUSION: This study establishes a novel genomic score to predict OS in NENs treated with ICI with important pan-cancer implications.

Humans↗
PubMed1993

Pathologic features of epidermoid carcinoma of the penis. A prospective study of 66 cases.

We report a whole-organ-section pathologic study of 66 cases of epidermoid carcinoma of the penis. Specimens were divided into three compartments: glans (G), coronal sulcus (COS), and foreskin (F) with 24, 4, and 12 histologic sections each. Four types of carcinomas were found: (a) superficially spreading (42%), a biphasic infiltrating and extensive carcinoma in situ usually involving more than one compartment and radially growing along the surface of G, BPS, F, or even urethra; (b) vertical growth (32%), unifocal high-grade, deeply invasive neoplasms with minimal or no carcinoma in situ component; (c) verrucous (18%), low-grade papillary or endophytic; and (d) multicentric (8%), two or more independent primary tumors separated by non-neoplastic mucosa. Inguinal lymph node metastasis were found in 82, 42, and 33% of pathologic types vertical growth, superficially spreading, and multicentric carcinomas, respectively; verrucous tumors did not show metastasis. The morphologic diversity of penile cancer may be related to different causative factors. Metastatic involvement suggests a distinctive biological behavior of the tumor. The widespread extension of superficially spreading and multicentric carcinomas to anatomical compartments indicate penile mucosa as one "field" prone to malignant transformation. These findings may be important for the selection of appropriate therapy and emphasize the need for a close follow-up of patients undergoing less than a complete removal of the three compartments.

Carcinoma, Squamous Cell↗
PubMed1989

Advances in the diagnosis of urothelial neoplasia.

Urothelial neoplasia is a unique cancer in that is consists of a spectrum of tumors with different biologic behaviors. The most common urothelial neoplasm is the low grade superficial papillary carcinoma or papilloma which may recur numerous times but does not result in significant morbidity or mortality. A variant of the superficial papillary carcinoma, which represents approximately 10% of the tumors, is the noninvasive papillary neoplasm which progresses to a less differentiated invasive transitional cell carcinoma (TCC). Considerable effort has been directed at identifying which of the superficial well differentiated papillary tumors will persist, recur, and progress to invasive cancer. Current approaches to identifying such tumors include cytogenetics, molecular biology, and flow cytometric DNA analysis. In the final group of bladder carcinomas, the high grade invasive neoplasms, evidence suggests that these life-threatening tumors arise de novo without identifiable precursors. Unfortunately, 75% to 90% of invasive TCCs are classified in this group, with the remaining minority progressing from preexisting recurrent superficial papillary carcinomas. Obviously the biologic behavior of these aggressive poorly differentiated tumors is life-threatening, and application of traditional diagnostic procedures and new technologies need to be directed at early diagnosis.

Biomarkers, Tumor↗