Anaplastic Component Research Articles

Genetic and Epigenetic Alterations in Tumor Progression in a Dedifferentiated Chondrosarcoma

In this case of a dedifferentiated chondrosarcoma, we searched for genetic or epigenetic alterations in both components of the tumor, the low grade chondroblastic component, and the high grade osteosacomatouscomponent. To date, only little is known about aberrant patterns of DNA methylation in chondrosarcomas. Microdissection was used as a valuable method for clearly separating the tissues. We examined CpG island methylation of 8 tumor suppressor genes and candidate tumor suppressor genes, which are involved in different pathways: cell cycle (p21WAF1, p16INK4, p14ARF), apoptosis (DAPK, FHIT), DNA repair (hMLH1), and cell adherence (E-Cadherin). We found p16INK4 and E-cadherin promotor methylation in the low grade chondroid compartment of the dedifferentiated chondrosarcoma. P16INK4, FHIT, and E-cadherin were methylated in the highly malignant osteosarcomatous compartment of the tumor. Earlier investigations of this chondrosarcoma showed p53 mutation and p53-LOH in the anaplastic component. As shown in this case, it was accompanied by Rb-LOH. Early methylation of p16IK4 and E-cadherin in the chondroid compartment could point to the monoclonal origin of demonstrated dedifferentiated chondrosarcoma. Further alterations, as shown in p53, Rb and FHIT, are responsible for the "switch" to a high grade anaplastic sarcoma.

Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma.

beta-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway. Objective.-To analyze beta-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas. beta-Catenin mutation in exon 3 was studied using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. beta-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic-type malignant fibrous histiocytomas were also studied. Dedifferentiated liposarcomas showed mutation in 2 cases (17%) and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a mutation in the well-differentiated component; this mutation was silent. The other case had mutations that differed between the 2 components. In well-differentiated liposarcomas, mutation was not seen in any of the cases (0/18; 0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8; 63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases, respectively, without any exact correlation between the cases. Cases with accumulation had a higher MIB-1 labeling index than those without, among both the sclerosing-type well-differentiated liposarcomas (P <.05) and the malignant fibrous histiocytomas. Our results suggest the possible involvement of beta-catenin activation caused by beta-catenin mutation in liposarcoma and malignant fibrous histiocytoma, but the contribution would seem to be different, depending on the tumor type. beta-Catenin accumulation is also thought to be related to cell proliferation in some of the cases.

β-Catenin Accumulation and Gene Mutation in Exon 3 in Dedifferentiated Liposarcoma and Malignant Fibrous Histiocytoma

Abstract Context.—β-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway. Objective.—To analyze β-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas. Design.—β-Catenin mutation in exon 3 was studied using polymerase chain reaction–single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. β-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic–type malignant fibrous histiocytomas were also studied. Results.—De...

Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas.

With the exception of benign cystadenomas, mucinous ovarian tumors are rare and heterogeneous neoplasms. They have been classified as either borderline tumors or carcinomas for almost 30 years. Subsequently, the borderline tumors have been subclassified into endocervical-like and intestinal types. The diagnostic criteria for distinguishing borderline tumors of the intestinal type from mucinous carcinomas have varied, making difficult the interpretation of prognostic information. More recently, a further subdivision of the former tumors into forms with only epithelial atypia and variants with focal intraepithelial carcinoma has been proposed. Consequently, in this study of 41 mucinous borderline tumors of intestinal type and 34 mucinous carcinomas, the former were also subdivided into 30 cases with mild to moderate atypia only and 11 with areas of intraepithelial carcinoma. All 30 purely borderline tumors were stage I tumors, and all 15 with follow-up information (including one case with microinvasion) were clinically benign. All 11 mucinous borderline tumors that had foci of intraepithelial carcinoma were also stage I neoplasms, and none of the eight patients with follow-up data (including one with microinvasive carcinoma) recurred. Thirty-four invasive carcinomas were subclassified into 15 expansile and 19 infiltrative subtypes. All 15 carcinomas with only expansile invasion were stage I; none of the 11 with follow-up data recurred. Three of nine patients with stage I infiltrative carcinomas with follow-up information had a fatal recurrence. Eight of the remaining 10 infiltrative carcinomas had extended beyond the ovary at the time of diagnosis (stages II and III); of the six patients with follow-up data, four died of tumor and two were alive with disease. In stage I carcinomas nuclear grade and tumor rupture correlated with unfavorable prognosis, but less than infiltrative invasion. However, all three fatal tumors were infiltrative carcinomas that had ruptured, and two contained grade 3 malignant nuclei. Combination of infiltrative invasion, high nuclear grade, and tumor rupture is a strong predictor of recurrence for stage I mucinous ovarian tumors. Among the 19 infiltrative tumors, 13 contained foci of anaplastic carcinoma. Of the seven patients with stage I tumors and follow-up data, only one patient whose tumor had ruptured intraoperatively had a fatal recurrence. The presence of anaplastic components in stage Ia (intact) carcinomas did not have an adverse effect in their outcome, even when the undifferentiated carcinomatous elements appeared in the form of mural nodules.

H-ras Oncogene Mutation in Dedifferentiated Chondrosarcoma: Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Analysis

Dedifferentiated chondrosarcomas, which are known for their poor prognosis, are characterized by conventional chondrosarcoma with high-grade anaplastic components. Activating mutations in ras genes are a common genetic abnormality in human malignancies. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 20 formalin-fixed paraffin-embedded chondrosarcomas, comprising 11 cases of conventional chondrosarcoma (six Grade 1 cases and five Grade 2 cases) and nine cases of dedifferentiated chondrosarcoma, using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. H-ras mutations were only seen in two out of the nine cases of dedifferentiated chondrosarcoma (2/9, 22%) and they were not seen in any of the cases of conventional chondrosarcoma (0/11, 0%). Dedifferentiated chondrosarcomas had a worse prognosis than conventional chondrosarcomas (P < .01); among the patients with dedifferentiated chondrosarcomas, those with H-ras mutation (n = 2) tended to have a worse prognosis than those without (n = 7), although the difference was not statistically significant (P = 0.068). Our results would seem to suggest that H-ras mutation may occur during the course of dedifferentiation and may also have some effect on malignant potential.

Dedifferentiated liposarcoma with chondroblastic osteosarcomatous dedifferentiation

We describe a rare case of dedifferentiated liposarcoma with features resembling chondroblastic osteosarcoma in the dedifferentiated component. The tumor was removed from the left thigh in a 78-year-old male. It consisted of a well-differentiated liposarcoma and an anaplastic component that contained numerous osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma. To our knowledge, only two cases similar to the divergent chondroblastic osteosarcomatous dedifferentiation of this disease have been reported in the literature.

Anaplastic spindle-cell squamous carcinoma arising in association with tall-cell papillary cancer of the thyroid: A potential pitfall.

Transformation of a differentiated thyroid carcinoma is an infrequent occurrence and is usually associated with a dismal prognosis. Following a long-standing history of papillary carcinoma of the thyroid, the patient in the present report developed anaplastic thyroid carcinoma. The anaplastic component initially arose in the setting of papillary carcinoma with tall-cell features, represented a very small proportion of the tumor, and was overlooked at the time of the original diagnosis. Several years later, the patient developed a recurrent neck mass. Fine-needle aspiration (FNA) of this mass revealed a population of atypical spindle cells arranged singly and in papillary clusters which lacked the classical cytologic features of papillary carcinoma of the thyroid. Histology of the resected mass revealed an unusual and recently described subtype of thyroid carcinoma, termed "anaplastic spindle-cell squamous carcinoma," which has been reported as occurring in association with tall-cell papillary carcinoma. The FNA findings of this unusual subtype of anaplastic thyroid carcinoma are presented. Diagn. Cytopathol. 1999;21:413-418.

Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma.

Membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as an activator of the proenzyme of matrix metalloproteinase 2 (MMP-2: gelatinase A), and has also been shown to play a crucial role in tumor invasion by activating proMMP2 in both lung and gastric carcinoma. The tissue inhibitor of metalloproteinase 2 (TIMP-2) plus the MT1-MMP complex also plays an important role in the activation of proMMP-2. In this study, the expressions of MT1-MMP, MMP-2 and TIMP-2 were evaluated in 10 enchondromas, 34 conventional chondrosarcomas, 5 clear-cell chondrosarcomas, 7 mesenchymal chondrosarcomas and 8 dedifferentiated chondrosarcomas. The expressions were immunohistochemically visualized on paraffin sections and the levels of expression were assessed semiquantitatively. The extent of staining was assessed by the extent score in order to determine the overall level of expression. The extent scores of MT1-MMP, MMP-2 and TIMP-2 in grade 2 chondrosarcoma were significantly higher than those in either enchondroma or grade 1 chondrosarcoma (P < 0.05). In conventional chondrosarcoma, significant correlations were found between the extent scores of MT1-MMP and MMP-2 (P < 0.001), MT1-MMP and TIMP-2 (P < 0.01), and MMP-2 and TIMP-2 (P < 0.01). The undifferentiated small round tumor cells of mesenchymal chondrosarcoma showed lower positive rates and extent scores for MT1-MMP (2/7, 0.7 +/- 0.5) and MMP-2 (3/7, 0.7 +/- 0.4) than for cartilaginous components of mesenchymal chondrosarcoma [MT1-MMP (4/7, 1.3 +/- 0.5) and MMP-2 (7/7, 1.9 +/- 0.3)] or conventional chondrosarcoma. In dedifferentiated chondrosarcoma, the extent scores of MT1-MMP, MMP-2 and TIMP-2 in low-grade cartilaginous components were not significantly different from those in conventional chondrosarcoma; however, the high-grade anaplastic components showed high extent scores for MT1-MMP, MMP-2 and TIMP-2, compared with the low-grade cartilaginous components of dedifferentiated chondrosarcoma or conventional chondrosarcoma. According to our results, the expression of MT1-MMP as well as that of MMP-2 or TIMP-2 demonstrated a significant correlation with the tumor grade in human cartilaginous tumors. Furthermore, the expressions of MT1-MMP, MMP-2 and TIMP-2 were also found to play a crucial role in invasion in the high-grade components of dedifferentiated chondrosarcoma.

Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki‐ras mutations provides evidence of a ductal origin

Undifferentiated carcinomas and osteoclast-like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast-like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki-ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast-like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast-like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid-pseudopapillary tumours. All undifferentiated carcinomas and osteoclast-like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid-pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast-like giant cell tumours were positive for vimentin. Ki-ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast-like giant cell tumour from which DNA could be successfully amplified. The Ki-ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast-like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast-like giant cell tumours share the same cytokeratin and Ki-ras features, they are probably derived from the same cell lineage. © 1998 John Wiley & Sons, Ltd.

Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki-ras mutations provides evidence of a ductal origin.

Undifferentiated carcinomas and osteoclast-like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast-like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki-ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast-like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast-like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid-pseudopapillary tumours. All undifferentiated carcinomas and osteoclast-like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid-pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast-like giant cell tumours were positive for vimentin. Ki-ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast-like giant cell tumour from which DNA could be successfully amplified. The Ki-ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast-like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast-like giant cell tumours share the same cytokeratin and Ki-ras features, they are probably derived from the same cell lineage.

Anaplastic variant of spermatocytic seminoma

Four examples of spermatocytic seminoma with a predominant anaplastic component occurred in men 33 to 43 years of age, without histories of cryptorchidism. The seminomas presented with painless testicular masses recognized 3 to 18 months before orchiectomy. Preoperative serum measurements of human chorionic gonadotropin and alpha-fetoprotein were negative. All tumors contained areas (10% to 30% of the tumor) in which the three cell types characteristic of conventional spermatocytic seminoma could be identified under light microscopy. The predominant anaplastic component also contained the three cell types, but the nuclei had prominent nucleoli with granular and filamentous chromatin. In addition, sheets of cells with vesicular nuclei and prominent nucleoli superficially resembling embryonal carcinoma were found. There were numerous large mononuclear and multinucleated giant cells with bizarre nuclei and prominent nucleoli, but no sarcomatous elements. Many normal and abnormal mitotic figures were present. Tunical and vascular invasion and extensive necrosis were constant features. Immunohistochemistry documented p53 protein overexpression in two tumors, but neoplastic cells were negative with immunostains for placenta-like alkaline phosphatase, leukocyte common antigen, neuron-specific enolase, alpha-fetoprotein, human chorionic gonadotropin, vimentin, and cytokeratins. Ultrastructural examination of the anaplastic component showed large rope-like nucleoli, but the cytoplasmic features were similar to those of conventional spermatocytic seminoma. Despite the presence of a major anaplastic component, no patient has developed metastasis. Larger series and longer follow-up are needed to understand the natural history of these neoplasms.

P53 in a Thyroid Follicular Carcinoma with Foci of Poorly Differentiated and Anaplastic Carcinoma

The clinical and pathologic features of a rare case of follicular carcinoma with small foci of poorly differentiated and anaplastic carcinoma are presented. Eight years after the removal of the primary neoplasm, the patient developed pulmonary and brain metastases that were predominantly composed of the poorly differentiated and anaplastic components. A comparative immunohistochemical and molecular analysis of p53 status in the follicular, poorly differentiated and anaplastic components of the tumor was performed. p53 immunostaining was restricted to the poorly differentiated and anaplastic areas. Single strand conformation polymorphism analysis (SSCP-PCR) from DNA obtained by microdissection demonstrated the presence of a mutation (TAT-->TGT; Tyr-->Cys) in codon 220, exon six of the p53 gene in the anaplastic component, that was absent in the well-differentiated follicular areas. The results of that study in this rare tumor support that p53 has a tumor progression role in thyroid tumorigenesis.

Dedifferentiated cystic nephroma with malignant mesenchymoma as the dedifferentiated component.

Cystic tumors of the kidney are uncommon and usually do not have solid areas. We report a predominantly cystic renal tumor with solid anaplastic component showing rhabdomyoblastic and cartilaginous differentiation in a 26-month-old girl. Terminology and pathogenesis of tumor progression are discussed along with a review of reports of tumors associated with cystic nephroma.

Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretoneurin in primary non-small-cell carcinomas of the lung

Fifty-three primary non-small-cell lung carcinomas (NSCLC) were immunohistochemically investigated with antibodies against chromogranin A, chromogranin B, and ecretoneurin. All 3 peptides were focally immunolocalized in 3 of 25 adenocarcinomas and in 2 of 6 large-cell anaplastic carcinomas in more than 20% of tumor cells. Two of 15 squamous-cell carcinomas showed chromogranin B reactivity in more than 20% of tumor cells. Neuroendocrine (NE) differentiation was also demonstrated in lymphnode metastases of large-cell anaplastic carcinomas, in 1 adenocarcinoma, and in 1 squamous-cell carcinoma, with NE differentiation of the respective primary tumors. All tumors with NE differentiation exhibited (large cell) anaplastic tumor areas. We conclude that NE differentiation should be immunohistochemically proven or excluded, particularly in NSCLC with anaplastic components. Chromogranin B and secretoneurin are proposed as useful additional neuroendocrine markers for demonstration of NE differentiation in lung carcinomas.

P53 expression in anaplastic carcinomas arising from thyroid papillary carcinomas.

To study the expression of p53 tumour suppressor gene in anaplastic carcinomas arising from thyroid papillary carcinomas. Formalin fixed, paraffin wax embedded tissues from four cases of anaplastic carcinomas associated with thyroid papillary carcinomas were studied by immunohistochemistry with two different p53 monoclonal antibodies. The anaplastic component showed nuclear immunostaining in two cases, but not in the other two. In all cases the papillary carcinoma component was negative. The results support the hypothesis that p53 stimulates tumour progression in thyroid tumours.

Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. Preliminary experience at the University of Tennessee, Memphis.

Between November 1989 and October 1992, 28 consecutive patients with glioblastoma multiforme (n = 18) or anaplastic astrocytoma (n = 10; includes one patient with oligodendroglioma with anaplastic astrocytoma component) were treated with interstitial iodine 125 (60 Gy over 6 days) and with concomitant cisplatin (via infusion on days 2-6 of the implant), then followed by hyperfractionated external beam irradiation (110 cGy delivered twice daily; 66 Gy planned total dose). Of 26 patients (60%) who received both 125I and HEBI, 15 are alive with no evidence of recurrent disease at a median follow-up of 18 months post-125I (range: 11 to 34 months). Four other disease-free patients succumbed to nontumor-related events. Two patients with local control had distant failure outside the HEBI treatment fields. Overall local control is 77%. Local failure occurred in 6 patients (23%) 2 to 11 months post-125I. Time to disease progression ranged from 4 to 18 months (median: 10 months). Survival (measured from the date of diagnosis) has ranged from 6 to 26 months (median: 15 months). All patients have maintained Karnofsky Performance Status within 20 points of their preimplant status, with the exception of a single patient who, following diagnosis of radiation necrosis and surgical intervention for symptomatic relief, had a 30-point drop in KPS. Radiation necrosis or persistent mass effect were noted by neuroimaging in seven patients, four of whom required surgical intervention following failed medical management. Ototoxicity, nephrotoxicity, peripheral nerve dysfunction, or hematologic toxicities have not been observed. This new innovative treatment approach offers a promising alternative to the normally dismal prognosis for patients with malignant gliomas.

Soft tissue sarcoma with additional anaplastic components. A clinicopathologic and immunohistochemical study of 27 cases

This clinicopathologic study concerns 27 cases of "dedifferentiated" soft tissue sarcoma (DSTS), including 14 liposarcomas, six leiomyosarcomas, five chondrosarcomas, and two rhabdomyosarcomas. In addition, the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three. The findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma (MFH). All tumors contained additional distinct anaplastic portions indistinguishable from MFH under conventional light microscopy, ultrastructurally, and in cases of immunoreactivity for alpha-1-antichymotrypsin and alpha-1-antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin. The desmin reactivity present in anaplastic portions of 14 DSTS and in eight de novo MFH is taken to mean that myofibroblasts are present in these tumors. The anaplastic components of DSTS are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast-like cells, histiocyte-like cells, and myofibroblasts. Nineteen patients died of tumor and four are alive and well 1.6, 1.7, 2.1, and 5.2 years after the initial treatment, respectively.

Fine‐needle aspiration cytology of sacrococcygeal chordoma

The fine-needle aspiration cytology (FNAC) of four cases of chordoma that were diagnosed preoperatively is presented. One of the cases showed anaplastic components along with the classical features of chordoma; this is probably the second case diagnosed with these features on FNAC. The cytologic features of classical chordoma include conspicuous extracellular matrix in the background. Polygonal cells, dissociated and in small groups, were identified in all cases. Physaliphorous cells were also prominently found in these cases. In addition, the case with anaplastic features showed very bizarre cells with profound multinucleation and the presence of intranuclear cytoplasmic inclusions. The diagnosis of chordoma was possible because of a high index of suspicion on clinical grounds and the use of special staining for confirmation.

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.

Adenocarcinoma of the uterine cervix with β-hCG production: A case report and review of the literature

The production of unexpected cell products, including the placental protein human chorionic gonadotrophin (hCG), has been reported in a variety of tumors at different anatomical sites. Some of the reported tumors have also expressed morphological features suggesting choriocarcinoma. Such is the case in this tumor of the uterine cervix which has a major component of anaplastic tumour with β-hCG production confirmed both by positive staining using immunoperoxidase techniques and by pre- and postoperative serum assays for β-hCG. The differing immunohistochemical features seen in the two components of the tumor are reported. The relationship of the anaplastic component to the adjacent mucinous adenocarcinoma in the present case, and to similar cases at other sites from the literature, is discussed.