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Histopathology 02/2008; 52(2):244-7. · 3.08 Impact Factor
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ABSTRACT: To evaluate the clinicopathological profile of 14 cases of nasal and paranasal sinusal adenocarcinoma, and to assess the usefulness of immunohistochemistry in the differential diagnosis of primary and metastatic intestinal-type adenocarcinoma.
Fourteen cases of nasal and paranasal adenocarcinoma, treated at IPOFG, Lisbon, between 1976 and 2002, were studied. Clinical records were reviewed and expression of cytokeratin (CK)7 and CK20 and of neuroendocrine markers was evaluated. The male : female ratio was 3 : 1, and the mean age of the patients was 65.3 years. Ten cases occurred in the paranasal sinuses. There was a history of professional exposure to dust in three patients. Twelve cases were high-grade intestinal type adenocarcinomas (ITAC) and two were low-grade. CK7 was present in 2/9 ITAC cases and CK20 in 8/9 ITAC and in cases of mixed and mucinous histology. All high-grade cases showed neuroendocrine differentiation. Seven of the 12 patients with high-grade adenocarcinoma died of the disease, with a mean follow-up of 47.4 months.
Nasal and paranasal adenocarcinoma mostly occurs in men in the 7th decade. ITAC is the most frequent histological type. The pattern of CK7/CK20 was not useful in the distinction between primary and metastatic intestinal adenocarcinoma. However, in the former, neuroendocrine differentiation proved to be a valuable tool in that distinction.
Histopathology 10/2004; 45(3):254-9. · 3.08 Impact Factor
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ABSTRACT: To investigate tenascin expression in salivary gland tumours. Tenascin is a matricellular protein that has been studied in several tumour types. Its expression has been correlated with tumour morphogenesis as well as with local invasiveness and tumour metastatic behaviour.
The distribution pattern of tenascin in a series of 63 pleomorphic adenomas (PA) and 20 carcinomas ex- pleomorphic adenoma (Ca ex PA) was studied immunohistochemically. Ten normal adult salivary glands were used as controls. Tenascin surrounded the excretory ducts of normal adult salivary gland tissue. It was absent in the basement membrane compartment of both benign and malignant mixed tumours. In the interstitial compartment of the extracellular matrix, the fibro-hyaline type expressed tenascin in a statistically significantly (P < 0.001) lower number of PA cases (25%) in comparison with both malignant and benign areas of Ca ex PA (75% and 90%, respectively). In the Ca ex PA group, a statistically significantly difference (P < 0.001) was found in the frequency of tenascin deposits around aggregates of neoplastic cells between metastasizing (73%) and non-metastasizing neoplasms (0%).
These findings strongly support the hypothesis that tenascin deposition is involved in the mechanisms of malignant transformation of pleomorphic adenomas into carcinomas as well as being associated with clinical disease progression.
Histopathology 08/2004; 45(2):187-92. · 3.08 Impact Factor
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ABSTRACT: Cytogenetic analysis of short-term cultured 44 basal cell carcinomas (BCC) revealed clonal karyotypic abnormalities in 38 tumors. Relatively complex karyotypes (at least four structural and/or numerical changes per clone) with unbalanced structural as well as numerical aberrations were found in eight (approximately 21%) of the BCC, while the remaining BCC (79%) had simple karyotypes (1 to 3 aberrations per clone). Numerical changes only were found in 16 tumors, 15 BCC displayed both numerical and structural aberrations, and the remaining 7 BCC showed only structural aberrations. Extensive intratumoral heterogeneity, in the form of cytogenetically unrelated clones, was found in 21 tumors, whereas related subclones were present in 10 tumors. In order to obtain an overall karyotypic picture in BCC, the findings of our previously published 25 BCC have been reviewed. Our combined data indicate that BCC are characterized by nonrandom karyotypic patterns. A large subset of BCC is characterized by nonrandom numerical changes, notably, +18, +X, +7, and +9. Structural rearrangements often affect chromosomes 1, 4, 2, 3, 9, 7, 16, and 17. A number of chromosomal bands are frequently involved, including 9q22, 1p32, 1p22, 1q11, 1q21, 2q11, 4q21, 4q31, 1p36, 2q37, 3q13, 7q11, 11p15, 16p13, 16q24, 17q21, and 20q13. When the genomic imbalance is assessed, it has been shown that several chromosome segments are repeatedly involved in losses, namely loss of the distal part of 6q, 13q, 4q, 1q, 8q, and 9p. A correlation analysis between the karyotypic patterns and the clinico-histopathologic parameters has been undertaken in the 44 BCC of the present series. The cytogenetic patterns show a significant correlation with tumor status (P=.025), that is, that cytogenetically more complex tumors are also those clinically the most aggressive. Also, the frequency of cytogenetically unrelated clones is significantly higher in recurrent BCC than that in primary lesions (P=.05). No clear-cut association has been found between the karyotypic patterns and histologic subtypes or tumor sites.
Cancer Genetics and Cytogenetics 01/2002; 131(2):109-19. · 1.39 Impact Factor
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ABSTRACT: Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) are low-grade adenocarcinomas of salivary glands with a putative common histogenesis from the intercalated ducts but featuring distinct histological appearances. Hybrid tumors containing areas with histological patterns of both neoplasms have been reported but, to our knowledge, the question of their genotypic similarity has not yet been approached. As part of an ongoing study on cytogenetic characterization of salivary gland tumors, from a group of 24 malignant neoplasms, three out of five cases of ACC and three of four cases of PLGA were selected for their similar karyotypic changes. All of them displayed chromosome 12 abnormalities, affecting the 12q12-q13 region in four (all ACC cases and one PLGA case), 12q22 in one PLGA case, and 12p12.3 in the remaining. From this group of neoplasms, one PLGA and one ACC showed the same t(6;12)(p21;q13). Our findings favor the concept that tumors of salivary glands displaying epithelial and myoepithelial phenotypes share a common histogenesis.
Cancer Genetics and Cytogenetics 08/2001; 128(2):130-6. · 1.39 Impact Factor
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ABSTRACT: Oral squamous cell carcinoma is a frequent disease with reserved prognosis, where the routinely evaluated morphological features lack a major correlation with prognosis. In order to assess the potential value of the immunoexpression of CD44 isoforms v3, v4-5, and v6, we studied it in a series of 56 consecutive cases of squamous cell carcinomas of the border of the tongue.
All the histological (World Health Organization grade, Bryne score, degree of keratinization, and pattern of stromal invasion) and immunohistochemistry (using monoclonal antibodies to CD44v) results were exclusively assessed at the deep invasion front of the neoplasms. Downregulation of CD44v was defined by focal or irregular staining of < 10% of the cells at the deep invasive front.
There was downregulation of CD44v3 in 37.5% of the cases, CD44v4-5 in 67.9%, and CD44v6 in 33.9%, occurring mostly in cases with low Bryne scores and graded as well-differentiated according to the WHO classification. Downregulation of CD44v was found to correlate with cell differentiation, tumor grade, and the pattern of neoplastic invasion.
Our findings in the present series point to the consideration that CD44v pattern and intensity of immunoexpression in the deep invasive front of squamous cell carcinoma of the tongue are mostly related to tumor grade, the features of stromal invasion, and to the presence of cervical lymph node metastases.
Journal of Surgical Oncology 03/2001; 76(2):115-20. · 2.10 Impact Factor
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C Jin,
C Martins,
Y Jin,
J Wiegant,
J Wennerberg,
M Dictor,
D Gisselsson,
B Strömbeck, I Fonseca,
F Mitelman,
H J Tanke,
M Höglund,
F Mertens
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ABSTRACT: Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.
Genes Chromosomes and Cancer 03/2001; 30(2):161-7. · 3.31 Impact Factor
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ABSTRACT: Between 1970 and 1998, 90 cases of male breast cancer with available pathological material were retrieved. The disease often presented in aged patients (median--66 years) and as advanced stage (stage III/IV-51%). Excluding stage IV disease, the neoplasia were predominantly ductal invasive carcinomas. NOS (not otherwise specified) (92%), grade 1 and grade 2 (94%), positive for estrogen and progesterone receptors (72% and 74%), negative for androgen receptors (100%), p53 negative (95%), c-erbB-2 negative (88%) and DNA aneuploid (73%). Assessment of disease outcome is determined by stage at time of diagnosis, and axillary lymph node status was the only parameter found to have a statistically significant correlation with either disease-free interval or overall survival (p < 0.001) by multivariate analysis. Clinically useful information on the probability of relapse can be added by determining c-erbB-2 (p = 0.02) and progesterone receptors (p = 0.04) in stage III and tumor ploidy (p = 0.04) in pN1 subgroups of patients.
Acta Oncologica 01/2001; 40(4):472-8. · 3.33 Impact Factor
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ABSTRACT: We studied the expression of CD44 isoforms immunoreactivity in normal human salivary gland tissue, aiming at its full characterisation in normal epithelial and myoepithelial cell types. Optical immunohistochemistry techniques using monoclonal antibodies anti-CD44v3, CD44v4/5 and, for CD44v6, together with immunoelectron microscopy, were performed in serous, seromucinous and mucinous glands. Normal human breast and a case of lactating breast adenoma were used for comparative purposes and as controls. CD44v3 was positive in acinar and myoepithelial cells and was absent in mucin-producing cells from the different gland types. CD44v4/5 was consistently negative in all types of salivary tissue. CD44v6 was constantly positive in serous acinar cells, focally positive in basal cells of ducts, and myoepithelial cells consistently expressed it. At the ultrastructural level, CD44v6 was localised to the interdigitating processes of acinar cells, whenever they were not covered by basal lamina and to the cell membrane facing myoepithelial cells. In myoepithelial cells, immunolabelling was found at the membranes facing the acinar cells and in caveolae present at this interface. No labelling was found at cell membranes of both acinar and myoepithelial cells in contact with basal lamina or at the luminal aspect of the former. The finding of CD44v3 and v6 in myoepithelium of normal salivary glands may argue in favour of the role of these molecules in the regulation of growth and renewal of normal tissues and, potentially, on the morphogenesis of salivary gland neoplasms.
Histochemie 01/2001; 114(6):483-8. · 2.59 Impact Factor
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ABSTRACT: This review summarizes research advances of cytometric, proliferation, cytogenetic, and molecular "objective" measurable parameters, as additional aids to prognostic information of salivary gland tumors provided by classical clinicopathologic indicators. Flow cytometric DNA ploidy and S-phase fraction seem to be of value as predictors of tumor behavior, aneuploidy, and high S-phase identifying an unfavorable clinical evolution of salivary gland neoplasms. Cell proliferation markers assessed by immunohistochemistry (e.g., PCNA, Ki-67) also appear to have predictive significance, but some conflicting results, in part related to technical procedures, limit their routine clinical application. Silver-stained methods (AgNORs) show a scarce value in estimating prognosis of salivary gland malignancies. p53 and c-erbB-2 as well as karyotyping, are of disputable benefit for clinical use, but the biologic information they provide give a better understanding on the molecular mechanisms involved in the development and progression of tumors. Further studies, with large databases, long follow-up information, uniformized histologic classification, and standardized methodologies, are needed to establish how these "objective" parameters would be of truly beneficial for the treatment of patients with salivary gland tumors.
Advances in Anatomic Pathology 10/2000; 7(5):294-306. · 3.92 Impact Factor
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American Journal of Surgical Pathology 04/2000; 24(3):469-71. · 4.35 Impact Factor
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ABSTRACT: We report the finding of clonal chromosome abnormalities in 13 short-term cultured squamous cell carcinomas (SCCs) of the skin. Intratumor heterogeneity, in the form of cytogenetically related (subclones) or unrelated clones, was detected in six tumors. Whereas clones with complex karyotypic changes were found in 6 tumors, clones with simple anomalies were observed in 10 tumors, and sometimes these clones coexisted with highly abnormal clones. Rearrangement of chromosome 8, in the form of isochromosome i(8q) or whole arm translocation, was the most common aberration, found predominantly in complex clones. Another recurrent feature, i.e., the centromeric rearrangement of chromosome 1, as isochromosome i(1q) or i(1p), or whole arm translocations, was always part of a complex karyotype. Homogeneously staining regions were found in two cases, one with a highly complex karyotype and the other with a simple karyotype. In order to obtain an overall karyotypic picture in SCC of the skin, the cytogenetic findings in 10 SCCs reported earlier were reviewed. The chromosomes most commonly affected were, in decreasing order, chromosomes 1, 11, 8, 9, 5, 3, and 7. Chromosomal sites most frequently rearranged were almost all pericentromeric: they were 8q10-q11, 1p10-q12, 5p10-q11, 11p15, and 9p10-q10. Recurrent anomalies were i(1q), i(8q), i(5p), i(1p), i(9p), and i(9q). Among them, only i(8q) and i(9q) might be assumed to be early genetic events, considering the fact that they could occasionally be identified in simple clones. The most frequent losses included part of or the entire chromosomes 2, 4, 9, 11, 14, 18, and 21, arm 8p, and chromosomes X, Y, and 13. Overrepresentation most frequently involved 1q, chromosome 7, and 8q. The characteristic karyotypic pattern observed in skin SCC was in line with the experience in several other carcinomas. Genes Chromosomes Cancer 26:295-303, 1999.
Genes Chromosomes and Cancer 01/2000; 26(4):295-303. · 3.31 Impact Factor
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ABSTRACT: Laminin and collagen have been studied in several tumor types and their immunomorphological expression correlated with tumor morphogenesis, local invasiveness, and metastatic behavior. In a series of 53 cases of pleomorphic adenomas (PA) and 16 cases of carcinomas ex-pleomorphic adenoma (Ca ex-PA), we investigated by immunohistochemistry the distribution pattern of laminin (lam) and collagen IV (col IV) at the basement membrane (BM) and the interstitial compartments, and their potential relationship with the metastatic behavior of Ca ex-PA. At the BM compartment, lam and col IV were expressed in 37 and 41 of all cases, respectively. In PA, there were lam and col IV around cell aggregates in 47.2% and 56.6% of the cases, respectively, and around isolated cells in 30.2% and 26.4%, respectively. In Ca ex-PA cases, both antigens were expressed in 56.3% and in 18.8% of the cases around cell aggregates and isolated cells, respectively. At the interstitial compartment, the fibro-hyaline matrix contained few lam in PA (19.2%) in contrast to Ca ex-PA (75%), including the benign areas of the neoplasms (90%), being the difference statistically significant (P < .001). In the Ca ex-PA group, a statistically significant difference was found on col IV deposits around tumor cell aggregates between metastasizing and nonmetastasizing neoplasms (P < .001). These findings support that laminin and collagen IV are involved in the process of malignant transformation of pleomorphic adenomas and their biological progression.
Human Pathlogy 09/1999; 30(8):964-9. · 2.88 Impact Factor
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ABSTRACT: Explanted cells from salivary gland tumors are particularly difficult to propagate in vitro and not efficiently immortalized by agents such as simian virus 40. Human papillomavirus 16 (HPV16) has been widely used to transform cells of epithelial origin, but its use for salivary gland cell transformation has not been described. In this study, we employed viral constructs containing the E6/E7 genes of HPV16 to infect and stably transform 9 salivary gland tumor cell cultures. Four of the tumor cell cultures were derived from benign tumors and 5 from malignant tumors. All of the original cell cultures were diploid; however, 6 contained subpopulations of cells with structural abnormalities. All 9 cell cultures were successfully transformed, and 8 were immortalized. The resulting cell lines have decreased serum requirements, exhibit a high proliferation rate, are E6/E7-positive and form colonies in soft agar. Immuno-histochemical and molecular studies confirmed that the transformed cells were indeed epithelial/myoepithelial in origin. All of the transformed cell lines had a diploid or near-diploid karyotype, and 2 contained the original translocated chromosomes in all cells. Our report represents a new application of the E6/E7 system in immortalizing salivary gland cell cultures, resulting in retention of the cellular features found in the native tissue without a general destabilization of the karyotype. These types of tissue culture resources should prove useful for positional cloning and functional studies of genes involved in salivary gland oncogenesis.
International Journal of Cancer 06/1999; 81(5):793-8. · 5.44 Impact Factor
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ABSTRACT: The authors studied a series of 97 consecutive cases of salivary gland tumors to investigate the correlation between the biologic parameters DNA ploidy and S-phase fraction (SPF) and the presumptive behavior of the neoplasms, as well as their potential clinical utility.
Histopathologic classification and grading of the tumors were evaluated according to 1991 World Health Organization criteria. DNA analysis was performed by flow cytometry in fresh material after propidium iodide staining. Clinical data and follow-up information were obtained from the clinical charts.
All the 71 benign salivary tumors showed a DNA diploid pattern. Seven carcinomas (7.2%) exhibited DNA aneuploidy. Eleven (42.3%) of 26 malignant tumors were considered low grade carcinomas, all of them being DNA diploid. Of the remaining 15 tumors, classified as high grade carcinomas, 7 showed DNA aneuploidy. SPF values ranged from 0.6% to 27.7%. A statistically significant difference was found between the mean SPF values of benign and malignant tumors, diploid and aneuploid tumors, and low grade and high grade carcinomas. When a cutoff value of 3% was used to discriminate histopathologic subgroups with prognostic impact, a significant difference was found between benign and malignant salivary tumors, high grade and low grade carcinomas, and high grade and benign tumors (P < 0.001).
The data from this study confirm the low incidence of DNA aneuploidy in salivary gland tumors and suggest the potential utility of SPF estimation in evaluating the clinical behavior of these neoplasms.
Cancer 02/1999; 85(2):273-81. · 4.77 Impact Factor
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Histopathology 04/1998; 32(3):279. · 3.08 Impact Factor
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ABSTRACT: Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better define the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, confirming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover approximately 2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.
Oncogene 02/1998; 16(1):83-8. · 6.37 Impact Factor
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ABSTRACT: Warthin's tumour is a peculiar subtype of monomorphic adenomas of the salivary glands, frequently cystic, and that characteristically associates an epithelial glandular cell component to a dense lymphoid infiltrate. Short-term cultures from 12 Warthin's tumours of salivary glands, including 5 previously reported cases were successfully karyotyped and clonal numerical and/or structural changes were detected in 7 of them (58%). 3 cases showed numerical abnormalities with loss of chromosomes Y (2 cases) and X (1 case). The remaining 4 abnormal cases presented the following structural changes: complex translocation t(11;19;16)(q21;p12;p13.3); reciprocal translocations t(6;8)(p23;q22) and t(6;15)(p21;q15) (2 cases); and 1p22, 3p26, 11p13 changes. In 1 case, clonal numerical deviations (+ 7 and -Y) were concurrent with the structural rearrangement t(6;8). Two of these aberrations are suggested to be Warthin's tumour-associated: 11q;19p translocation has already been described in 3 cases, and structural rearrangements of 6p23 have also been reported in another case. Our study extends the cytogenetic information about Warthin's tumour and identifies two recurrent abnormalities --6p rearrangements and t(11;19)--specific for this salivary neoplasm.
Oral Oncology 10/1997; 33(5):344-7. · 2.86 Impact Factor
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ABSTRACT: To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and progression of salivary tumours with myoepithelial differentiation.
233 tumours from 211 patients were studied. These included 76 primary and 24 recurrent adenocarcinomas (polymorphous low grade adenocarcinoma, 13; epithelial-myoepithelial carcinoma, 19; adenoid cystic carcinoma, 56; and basal cell adenocarcinoma, 12) and 133 pleomorphic adenomas and myoepitheliomas, 96 being primary and the remaining recurrent tumours. All cases were formalin fixed and paraffin wax embedded. A StrepABC peroxidase method and polyclonal c-erbB-2 and p53 specific antisera were used.
Cell membrane staining of c-erbB-2 was not found in any benign or malignant tumour. There was p53 protein accumulation in one primary and one recurrent pleomorphic adenoma and in 10 adenocarcinomas (polymorphous low grade adenocarcinoma, one; epithelial-myoepithelial carcinoma, one; adenoid cystic carcinoma, five; and basal cell adenocarcinoma, three), three of them being recurrences.
The c-erbB-2 and p53 proteins are not involved in the pathogenesis of pleomorphic adenoma and myoepithelioma and do not constitute biomarkers in assessing the risk of recurrence. c-erbB-2 is not involved in the genesis of low grade salivary neoplasia with myoepithelial differentiation. The percentage of this type of neoplasia with p53 accumulation is low (10%) and does not appear to be related to tumour recurrence.
Journal of Clinical Pathology 09/1997; 50(8):661-3. · 2.31 Impact Factor
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ABSTRACT: We used three markers of cell proliferation mitotic counts, mitotic index and expression of proliferating cell nuclear antigen--to assess the proliferative activity of a series of 78 low-grade salivary adenocarcinomas with myoepithelial participation classified according to: their histological type, the predominant architectural type, and the predominant cytological type. The series included adenoid cystic carcinomas (40), epithelial-myoepithelial carcinomas (19), polymorphous low-grade adenocarcinomas (12) and basal cell adenocarcinomas (7). The proliferation indicators were found to be similar in the first three groups, being significantly lower than in the last. Tumours formed by basal cells had statistically significant higher mitotic indexes than those predominantly composed of clear cells of myoepithelial type and ductal cells. Tubular tumours, irrespective of the histological classification of the neoplasm, had proliferation indexes similar to those found in cribriform neoplasms. Solid tumours, whether formed by ductal or clear myoepithelial-type cells, had higher indexes than the neoplasms with differentiated (cribriform and tubular) patterns. The highest mean values for every proliferation indicator used were found in tumours with solid organization that were predominantly formed by basal cells. These results agree with the hypothesis that cell proliferation is inversely related to neoplastic differentiation. The identification of the prevalent cell phenotype and architecture may extend our knowledge from adenoid cystic carcinoma, whose solid variant carries a worse prognosis, and supports that the usual classification of this group of salivary adenocarcinomas would benefit to be complemented with information on tumour architecture and cellular composition.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/1997; 430(3):227-32. · 2.49 Impact Factor
