s ?gnised types or, as we should prefer to call them, genera, ^Cles and varieties of tumours. In carrying out this project, \\ve Particularly when making out the series of indexes that e required, we soon made acquaintance with difficulties of enclature and of classification. These difficulties occur 0Ve?*t daily in the course of routine examinations and are th^00.1116 or evaded in varying fashion. It may be argued cl \\ln the present state of our knowledge, a satisfactory j^Slficati?n of tumours is not possible, or that it is easy to Co^ e Ossifications from an armchair for one who is not deeply p0j^erned in using them. But those remarks seem to miss the

Classification of Tumours.

: OVCA1 and OVCA2 were first identified by us as candidate tumor suppressor genes, due to the fact that they map to a critical region of frequent allelic loss in breast and ovarian cancer at l7p13.3. Our studies have shown that OVCA1 is mutated in some tumor cell lines, and its protein levels are decreased or lost in nearly 40% of breast and ovarian adenocarcinomas, while OVCA2 appears to be unaffected. Expression of low levels of exogenous OVCA1 results in dramatic growth suppression and decreased levels of cyclin D1. We used a yeast-2-hybrid screen to identify OVCA1-associating proteins. One such protein, RBM8, was identified. Amino acid sequence indicates that RBM8 is a new member of an RNA-binding motif (RBM) family which is highly conserved evolutionarily. RBM8, also know as Y14 has been shown to be a shuttling protein that preferentially associates with spliced mRNA in the nucleus and remains associated with newly exported mRNA in the cytoplasm. Mutational analysis revealed no somatic mutations in ovarian tumor however, our current studies suggest that RBM8 is involved in mRNA export and that its levels may be significantly upregulated in most transformed cells. Overall, our studies indicate that altered expression and/or post-translational modifications of OVCA1 is associated with the development of breast and ovarian tumors and suggest a potentially new mechanism for the inactivation of tumor suppressors in cancer.

/pdf/identification-of-two-candidate-tumor-suppressor-genes-on-3pmn5z8gqk.pdf

Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13.3: Assessment of Their Roles in Breast and Ovarian Carcinogenesis

A 50-year-old man was admitted with a diagnosis of acute appendicitis on January, 5, 1984 and an appendectomy was performed on the same day. The acutely inflamed appendix measured 7 cm in length, and a gross tumor, was seen at the apex. Histologic examination of the gross tumor, which was 1.7 cm in diameter, revealed a neoplasm representing a goblet cell carcinoid. Silver impregnation by both the Grimelius and Masson-Fontana methods disclosed a positive reaction in some neoplastic cells. Electron microscopically, endocrine granules with both limiting membranes and ahlos, 100-210 nm in diameter, were present in the neoplastic cells, Because of the relatively large size of the tumor and neoplastic invasion to the mesoappedix in this case and, in addition, the possible malignant nature of carcinoid tumor, ileoascendocolectomy was performed as an additional operation.

Goblet cell carcinoid of the appendix

Distinct HIC1-SIRT1-p53 loop deregulation in lung squamous carcinoma and adenocarcinoma patients.

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.

https://erj.ersjournals.com/content/erj/47/6/1829.full.pdf

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome.

Deletions in the short arm of chromosome 17 (17p) involving the tumor suppressor TP53 occur in up to 20% of diffuse large B-cell lymphomas (DLBCLs). Although inactivation of both alleles of a tumor suppressor gene is usually required for tumor development, the overlap between TP53 deletions and mutations is poorly understood in DLBCLs, suggesting the possible existence of additional tumor suppressor genes in 17p. Using a bacterial artificial chromosome (BAC) and Phage 1 artificial chromosome (PAC) contig, we here define a minimally deleted region in DLBCLs encompassing approximately 0.8 MB telomeric to the TP53 locus. This genomic region harbors the tumor suppressor Hypermethylated in Cancer 1 (HIC1). Methylation-specific PCR demonstrated hypermethylation of HIC1 exon 1a in a substantial subset of DLBCLs, which is accompanied by simultaneous HIC1 deletion of the second allele in 90% of cases. In contrast, HIC1 inactivation by hypermethylation was rarely encountered in DLBCLs without concomitant loss of the second allele. DLBCL patients with complete inactivation of both HIC1 and TP53 may be characterized by an even inferior clinical course than patients with inactivation of TP53 alone, suggesting a functional cooperation between these two proteins. These findings strongly imply HIC1 as a novel tumor suppressor in a subset of DLBCLs.

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma.

SUMMARY Uterine tumors resembling ovarian sex cord tumors (UTROSCT) have an uncertain histogenesis. Although generally considered to be benign, they metastasize in some cases. We report the case of a 53-year-old woman who presented with vaginal bleeding. Clinical examination revealed a tumor sized 1.5 cm in diameter localized in the subendometrial region of the uterine wall. Histologically, the tumor consisted of epithelioid oval cells arranged in solid nests, trabeculae and ribbons. Immunohistochemically, approximately 1% of tumor cells expressed strong desmin positivity, calponin in 10% of cells, WT1 in 80% cells, and Ki-67 was positive in about 5 % of tumor cells. All the other immunohistochemical reactions applied including anti-cytokeratin antibodies were negative. The RT-PCR method for identification of the JAZF1-JJAZ1 fusion transcript was negative. In one lymph node in the right iliac artery region, a metastasis of UTROSCT was found. This finding adds to the previously reported UTROSCT cases with metastatic spread.

/pdf/uterine-tumors-resembling-ovarian-sex-cord-tumors-utrosct-3xxukfh0hm.pdf

Uterine tumors resembling ovarian sex cord tumors (UTROSCT). Report of a case with lymph node metastasis.

SUMMARY Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is a rare condition affecting mostly women in the fifth and sixth decades of life. Here we present a case of its accidental finding in the lung parenchyma of a 56-year-old non-smoker female. In the periphery of the right middle lobe, linear and nodular proliferations were detected in the wall of the small bronchi and terminal and respiratory bronchioles. Under the pleura, several tumorlets were located. Immunohistologically, neuroendocrine cells were positive with antibodies against chromogranin A, synaptophysin, CD56, serotonin (weak positivity of some cells only), calcitonin, GRP/bombesin, cytokeratin 7 and TTF-1.

/pdf/diffuse-idiopathic-pulmonary-neuroendocrine-cell-hyperplasia-1vsq2hv461.pdf

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Case report and review of literature

Large cell neuroendocrine carcinoma of the urinary bladder is rare In the last five years, we have had the opportunity to see this type of cancer in an 88-year-old and in a 66-year-old males In both cases, transurethral resection of carcinoma of the bladder was carried out In the first case, urothelial carcinoma was detected and deeper in the bladder wall, large cell neuroendocrine carcinoma structures were found In the second case, the bladder was only infiltrated with large cell neuroendocrine carcinoma Both tumors expressed NSE, CD56 and synaptophysin Other markers, such as those against calcitonin, chromogranin, PP, VIP, serotonin, gastrin, glucagon and somatostatin did not react with the tumor In the first case, no tumor dissemination was found; in the second case, clinical methods confirmed dissemination into the liver, left adrenal gland, spleen and paracaval lymph nodes Given his age, the first patient only received symptomatic therapy The other patient underwent chemotherapy and his condition is stable Paraneoplastic manifestations of the tumors were not clinically found Histogenetic origin of neuroendocrine tumors is not fully clarified In some cases, tumor development is thought to be associated with Brunns nests, cystitis cystica and urothelial carcinoma stem cells

Primary large cell neuroendocrine carcinoma of the urinary bladder

Background and Aim: The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL. Methods: The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting. Results: In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting. Conclusions: There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.

https://jcp.bmj.com/content/jclinpath/62/10/948.full.pdf

Jirka Mačák

Papers

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT). Report of a case with lymph node metastasis.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Case report and review of literature

Primary large cell neuroendocrine carcinoma of the urinary bladder

Complex analysis of cyclin D1 expression in mantle cell lymphoma: two cyclin D1-negative cases detected