Iris melanoma with ciliary body infiltration presenting as a presumed chronic unilateral inflammatory glaucoma. The challenges of iris tumor biopsy assessment.

Uveal melanoma is the most common primary malignancy of the eye in adults. It may involve the choroid and ciliary body, and in only 2-3% of cases it involves the iris. We present a case of a 56-year-old patient with a 6-year history of unilateral, inflammatory, refractory glaucoma of the right eye. Due to acquired heterochromia and heterogeneous thickness of the iris, iris melanoma was suspected, but the incisional biopsy did not confirm the diagnosis. In the next months, the lesion enlarged and the eye globe was enucleated. Histopathological examination revealed an iridociliary melanoma with annular growth pattern.

Outdoor work as a risk factor for high-grade cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: While it is clear that individuals with outdoor occupations are at a significantly greater risk of developing cutaneous squamous cell carcinoma (cSCC), no previous studies have investigated the potential association between the tumour grade and occupation in this patient population. AIM: To assess occupation as a risk factor for the development of high-grade cSCC. Secondarily, to determine the association between the tumour grade and other clinical characteristics. MATERIAL AND METHODS: Retrospective analysis of 256 patients treated for head and neck cSCC at our institution in 2007-2016. The following patient characteristics and variables were assessed: age; sex; tumour location and grade; profession; and education level. A univariate analysis was performed to assess the association between each study variable and grade 3 tumour differentiation. RESULTS: The following variables were significantly associated (p < 0.05) with grade 3 (G3) cSCC tumours: outdoor work vs. indoor work; primary school vs. high school education; and age. Additionally, patients with low-grade (G1) tumours were significantly younger (mean age: 72) than patients with high-grade (G3) tumours (mean age: 79) (p = 0.046). CONCLUSIONS: To our knowledge, this is the first study to assess the variables associated with the tumour grade among outdoor workers. These findings suggest that outdoor workers who develop cSCC are at a greater risk of developing more aggressive cancers. These findings provide additional support for classifying cSCC as an occupational disease. Early education about the dangers of sun exposure during the first years of school is essential to minimize the risks of developing high-grade skin cancer.

Patterns of treatment failure in salivary gland cancers.

AIM: The purpose of the study was to publish our experience of salivary gland cancer treatment with large number of patients treated at a single institution. BACKGROUND: Salivary gland cancers are rare tumors of the head and neck representing about 5% of cancers in that region and about 0.5% of all malignancies. Due to the rarity of the disease, most of the studies regarding treatment outcome consist of low number of patients, thus making it difficult to draw conclusions. MATERIAL AND METHODS: 115 patients with primary salivary gland cancer were included in a retrospective study. The subsites of tumor were the parotid gland (58% patients), submandibular gland (19%) and minor salivary glands (23%). All patients underwent primary surgical resection. The following were collected: age, stage of the disease, T status, N status, grade of tumor, perineurial invasion, lymphovascular invasion, extracapsular spread, final histological margin status and postoperative treatment. Details of local, regional or distant recurrence, disease free survival and overall survival were included. RESULTS: The majority (65%) of patients presented in early stage, T1 and T2 tumors. 81% of patients were N0. Free surgical margins were achieved in 18% of patients, close in 28% patients and positive surgical margins in 54% (62) patients. Factors that significantly increased the risk of recurrence: T stage (p = 0.0006); N-positive status (p < 0.0001); advanced stage of the disease (p < 0.0001); high grade of tumor (p = 0.0007); PNI (p = 0.0061); LVI (p = 0.0022); ECS (p = 0.0136); positive surgical margins (p = 0.0022). On multivariate analysis, high grade of tumor and positive surgical margins remained significant independent adverse factors for recurrence formation. CONCLUSIONS: This report shows a single institution results of oncological treatment in patients with malignant salivary gland tumors, where positive surgical margins strongly correlate with patients' worse outcome. Whether to extend the procedure, which very often requires sacrificing the nerve is still a question of debate.

The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?

CONTEXT: An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5-year disease-free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo-x) would be associated with a lower incidence of the BRAF(V600E) mutation. OBJECTIVES: To evaluate the frequency of the activating mutation BRAF(V600E) in low-risk papillary thyroid microcarcinoma (pT1aNo-x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis. STUDY DESIGN: BRAF(V600E) was characterized in 113 PTC patients diagnosed with pT1aNo-x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele-specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue. RESULTS: The BRAF(V600E) mutation was detected in 78 of the 113 pT1aNo-x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12-year study (January 2001 to December 2012). CONCLUSIONS: The presence of the activating BRAF(V) (600E) mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF-positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.

Testing new susceptibility genes in the cohort of apparently sporadic phaeochromocytoma/paraganglioma patients with clinical characteristics of hereditary syndromes.

BACKGROUND: Phaeochromocytoma (PCC) and paraganglioma (PGL) can occur sporadically or as a part of familial cancer syndromes. Red flags of hereditary syndromes are young age and multifocal tumours. We hypothesized that such patients are candidates for further molecular diagnosis in case of normal results in 'classical' genes. MATERIAL AND METHODS: We selected patients with PCC/PGL under the age of 40 and/or with multiple tumours. First, we tested the genes RET, VHL, NF1, SDHB, SDHC and SDHD. Patients without mutations in these genes were tested for mutations in MAX, TMEM127 and SDHAF2. RESULTS: In 153 patients included, mutations were detected in the classical genes in 72 patients (47%) [RET-22 (14%), VHL-13 (9%), NF1-3 (2%), SDHB-13 (9%), SDHC-3 (2%), SDHD-16 (11%), SDHB large deletions- 2 (1%)]. One patient with MAXc.223C>T (p.R75X) mutation was detected. It was a male with bilateral, metachronous phaeochromocytomas diagnosed in 36 and 40 years of age. Remarkably, he showed in the period before the MAX gene was detected, a RET p. Y791F variant. During 10-year follow-up, we did not find any thyroid abnormalities. LOH examination of tumour tissue showed somatic loss of the wild-type allele of MAX. CONCLUSION: Analysis of the MAX gene should be performed in selected patients, especially those with bilateral adrenal phaeochromocytoma in whom mutations of the classical genes are absent. Our study provides with further support that Y791F RET is a polymorphism.

Comparison of two different immunohistochemical algorithms identifying prognostic subgroups of DLBCL.

In this study we analyzed the prognostic value of single and combined immunohistochemical markers, according to algorithms proposed by Hans et al. and Muris et al. in 66 de novo diffuse large B-cell lymphoma (DLBCL) cases. The main aim of our study was to compare usefulness of these two immunohistochemical algorithms for the subdivision of DLBCL into prognostically relevant subgroups. Cases classified as germinal centre B-cell (GCB) had a significantly lower risk of death (p = 0.008) compared with the non-GCB group. The 5-year overall survival (OS) rate was 85% for the GCB group and only 30% for the non-GCB group (p = 0.003). Furthermore, division into the GCB and non-GCB group predicted prognosis in cases with low International Prognostic Index (IPI) (p = 0.03). GCB patients with a low IPI score had a significantly better OS than those from the non-GCB group (93% versus 45%) (p = 0.02). Although the 5-year OS of favourable group 1 from Muris algorithm was slightly better than in group 2, the difference was not significant (p = 0.241). In summary, our results indicate that the algorithm of Hans et al. has a significantly better prognostic value. By using immunohistochemistry and this algorithm, we can subclassify DLBCL into prognostically distinct subgroups and further refine the prognosis based on IPI.

The clinical course of poorly differentiated thyroid carcinoma (insular carcinoma) - own observations.

INTRODUCTION: Poorly differentiated thyroid carcinoma (PDTC, insular carcinoma) occurs rarely. It is described with more aggressive behaviour, poorer prognosis, and higher mortality than well differentiated thyroid carcinoma (WDTC). The aim of this study was to evaluate the clinical course of patients with PDTC, in addition to frequency, clinical stage at the time of diagnosis and the possibility of radical surgical resection, the necessity and kind of complementary treatment, occurrence of distant metastases, and the survival of patients. MATERIAL AND METHODS: The study involved 14 patients (9 females, 5 males) diagnosed and treated for PDTC between 2000 and 2009, aged 38 to 78 years. The medical records of patients with PDTC were analyzed to estimate assumed parameters according to the purpose of the study. RESULTS: PDTC was diagnosed in 14 among 801 patients with thyroid carcinoma (1.75%). Clinical stages (UICC 2002) at the time of diagnosis were as follows: 3 patients - pT(1-2)N(o-x)M(x) (21.5%); 10 patients - pT(3 4)N(x o 1)M(x-1)(71.4%); and 1 was unresectable - T(x)N1M1 (7.1%). Total thyroidectomy was achieved in 9 patients (64.3%), and 4 patients (28.6%) received non radical surgery. Complementary radioiodine treatment was given to 12 patients (85.8%). Radiation therapy of the neck was applied to 7 patients, palliative radiotherapy of the brain to 1 patient, and chemotherapy to 1 patient. Distant metastases to the lung and to the brain at diagnosis were observed in 2 patients (14.3%). During follow-up of 3-62 months lung metastases were observed in 4 patients (28.6%), three patients were observed above 5 years as disease-recurrence free (21.5%), but in one patient after 5 years and 2 months distant metastases were diagnosed. Three patients died after 2-30 months (21.5%), 2 patients were lost for control, and in the remaining 6 follow-up lasted for less than 5 years. CONCLUSIONS: Poorly differentiated thyroid carcinoma is still a challenge both for pathologists and clinicians. Infrequent prevalence, more aggressive course, and poorer prognosis constitute major problems for the clinicians.

The role of PET-CT scan with somatostatin analogue labelled with gallium-68 (68Ga-DOTA-TATE PET-CT) in diagnosing patients with disseminated medullary thyroid carcinoma (MTC).

INTRODUCTION: Calcitonin is a very sensitive marker of medullary thyroid carcinoma (MTC). High concentrations of basal or pentagastrin stimulated calcitonin in patients with MTC is a signal of recurrence or metastatic disease. Detection of metastatic foci remains a diagnostic and therapeutic challenge. The aim of the study was to present examples of the use of 68Ga-DOTA-TATE PET-CT examinations in the diagnosis of patients with MTC and concomitant elevated serum calcitonin concentrations. Initially the study involved eight patients with MTC and elevated basal or stimulated calcitonin, in which earlier diagnostic imaging was negative for metastasis: neck ultrasound, chest and mediastinal CT scan, liver MRI, bone scintigraphy, and ¹8F-FDG-PET. A total body scan was performed using 68Ga-DOTA-TATE PET-CT. Two patients with positive diagnostic imaging tests were referred for surgery including resection of cervical lymph nodes with histopathological examination for assessment of metastases. CONCLUSIONS: On the basis of the presented cases we conclude that PET-CT scan with somatostatin analogue labelled with gallium (68Ga-DOTA-TATE PET-CT) may be useful in the diagnostic imaging of patients with disseminated MTC.

Prognostic markers in salivary gland cancer and their impact on survival.

BACKGROUND: The role of molecular markers in salivary gland carcinoma (SGC) is not well understood. We evaluated molecular marker expression and their prognostic value. METHODS: Immunohistochemical analysis of 124 tumor specimens was performed to determine expression of androgen (AR), estrogen (ER), and progesterone (PR) receptors and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 receptor (PD-L1), and PD-L1 in tumor-infiltrating mononuclear cell (TIMC). Survival outcomes (disease-free survival [DFS] and overall survival [OS]), pT and N classification, margin status, and treatment failure were assessed. RESULTS: Most patients (78; 62.9%) had early-stage SGC. AR positivity and EGFR positivity were detected in 21.0% and 78.6%, respectively, of tumors. AR positivity and PD-L1 negativity were associated with locally advanced disease. PD-L1-negativity was associated with higher recurrence (38.5% vs 0%; P < .001) and worse DFS. OS and DFS were worse in patients with AR+ or HER2+ disease. CONCLUSIONS: Several molecular markers-AR and HER2 positivity and PD-L1 negativity-were associated with worse clinical outcomes. Prospective, multi-institutional trials are needed to determine the prognostic value of these markers.

Pleomorphic adenoma of salivary glands does not appear to be a BRCA-1-dependent tumour in a Polish cohort.

BACKGROUND: The aim of the study was to examine whether pleomorphic adenoma of salivary glands can occur on the basis of constitutional BRCA-1 mutations. MATERIALS AND METHODS: Two hundred and sixty-eight patients affected by mixed tumour of salivary glands were examined for occurrence of three BRCA-1 mutations dominating in Poland. RESULTS: BRCA-1 mutation was detected in only one of the patients, a female affected by breast cancer and pleomorphic adenoma of parotid gland. Parotid gland tumour showed clinical and histopathological features of typical pleomorphic adenoma with no morphological features of high-grade malignancy, which are characteristic of BRCA-1-dependent tumours. CONCLUSION: Considering the low frequency of BRCA-1 mutation in the examined group and also the absence of features characterizing BRCA-1-dependent tumours in the only BRCA-1-positive case, pleomorphic adenoma of salivary glands should not be recognized as a BRCA-1 dependent tumour.

Molecular cytogenetic analysis of chromosome aberrations in desmoid tumors.

To date there are only few reports concerning chromosomal changes in desmoid tumors. To extend the knowledge in this field we examined 19 samples from the patients diagnosed with desmoid tumors. In the present study formalin-fixed and paraffin-embedded desmoid tumors were analyzed using fluorescence in situ hybridization (FISH) with a-satellite probes for chromosomes X, Y, 8 and 20. Chromosomal abnormalities were found in 6 cases, both abdominal and extra-abdominal tumors. FISH studies revealed one case of trisomy 8 and trisomy 20. In four patients we have identified monosomy 20. Our findings confirm earlier reports concerning the diversity of chromosomal changes in desmoid tumors and might suggest that both groups of abdominal and extra-abdominal tumors are genuine neoplasms.

[Salivary duct carcinoma--a clinicopathological analysis of five cases]. / Rak przewodowy gruczolów slinowych (salivary duct carcinoma) - charakterystyka kliniczna i patologiczna 5 przypadków.

The 5 cases of salivary duct carcinoma (SDC); very rare, but distinct group of highly malignant salivary gland tumor are presented, and difficulties with pathological and clinical diagnosis is discussed. The SDC developed in single cases in parotid salivary gland, submandibular salivary and in mucosa of maxillary sinus, pyriform fossa and oral cavity (check). In 3 cases the second malignant tumor was present--synchronously (SDC + pleomorphic adenoma in parotid gland; SDC + squamous cell carcinoma in hypopharynx) or metachroneously (squamous cell carcinoma of upper lip followed by SDC). In one case the high levels of PSA suggesting of metastases from unknown primary within the prostate gland, or PSA expression related to SDC was observed. The four patients received radical treatment - surgical resection followed by radiotherapy; in one case only palliative treatment was applied, due to patient's poor general condition and high advancement of the primary disease. The observation ranged from 10 to 77 months (average time--31 months). The one patient died 13 months after diagnosis and palliative treatment. The three patients are alive with distant metastases to the lung and bones (77, 38 and 18 months after primary treatment was completed). Only one patient with 10 months observation after treatment is living without symptoms of recurrence or metastases.

Distal intramural spread of rectal cancer after preoperative radiotherapy: the results of a multicenter randomized clinical study.

PURPOSE: To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer. METHODS AND MATERIALS: A total of 316 patients with T(3-4) primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS. RESULTS: The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001). CONCLUSIONS: Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

Aggressive fibromatosis (desmoid tumors): definition, occurrence, pathology, diagnostic problems, clinical behavior, genetic background.

Aggressive fibromatosis, usually called desmoid tumor develops from muscle connective tissue, fasciae and aponeuroses. This neoplasm is composed of spindle (fibrocyte-like) cells. As regards the site, aggressive fibromatoses can be divided into: extra-abdominal in the area of the shoulder and pelvic girdle or chest and neck wall; abdominal in abdominal wall muscles; intra-abdominal concerning pelvis, mesentery connective tissue or retroperitoneal space. Desmoid tumor is a neoplasm which rarely turns malignant and is non-metastasizing but demonstrates ability to local infiltration into tissue and is characterized by high risk of recurrence (25-65%) after surgical treatment. Desmoid tumor etiology is uncertain. This neoplasm occurs in sporadic (idiopathic) form and is also associated with some familial neoplastic syndromes. Most sporadic cases of aggressive fibromatosis contain a somatic mutation in either the adenomatous polyposis coli (APC) or beta-catenin genes. Sporadic tumors are more frequent in women than in men from 2 : 1 to 5 : 1. In about 10-15 per cent of patients with familial adenomatous polyposis (FAP), aggressive fibromatosis is a parenteral manifestation of this familial syndrome conditioned by APC gene mutation. Abdomen injury--most frequently due to surgery is said to play an important role in the initiation of fibrous tissue proliferative process in the cases of abdominal and intra abdominal forms. High cells growth potential with relatively high local malignancy is observed in about 10% of cases with sporadic tumors as well as in those FAP-associated.

Analysis of TGF-beta protein expression in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis, usually termed desmoid tumor, develops from muscle connective tissue, fasciae and aponeuroses. Aggressive fibromatosis located in various parts of the body demonstrates differentiated biological behavior. Abnormalities in TGF-beta expression are very common in many disease processes, including neoplasms. Immunohistochemical analysis employing a monoclonal antibody against TGF-beta was performed on archival material, consisting of 38 cases of aggressive fibromatosis, among which 23 represented abdominal, 11 extra-abdominal and 4 intra-abdominal localizations. The sections for immunohistochemical study were stained using the streptavidin-biotin (ABC) method. The average percentage of cells positively stained for TGF-beta protein was 40.2% in the group of extra-abdominal, 58.5% in the group of abdominal and 72.8% in the group of intra-abdominal localizations. There were significant differences observed between the analyzed groups of desmoid tumor (p<0.05). A positive cytoplasmic reaction for TGF-beta was noted in 65.8% (25/38) of the aggressive fibromatoses. Overexpression of TGF-beta protein was noted in 39.5% (15/38) of the aggressive fibromatoses. High expression noticed in desmoid fibroblasts might indicate that this protein plays a crucial role in the development of aggressive fibromatosis.

Analysis of p27KIP1 protein and Ki-67 expression in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis (desmoid tumor) is an uncommon locally invasive non-metastasizing neoplasm lesion. Desmoid tumor consists of fibroblasts, miofibroblasts and a significant amount of extracellular matrix. p27KIP1 (p27) protein is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family that regulates progression through the cell cycle. In various human neoplasms the decreased level of p27 was observed. There were analysed 42 specimens of aggressive fibromatosis, in which there were 24 abdominal and 18 extra-abdominal cases. There was performed immunohistochemical analysis employing a monoclonal antibody against p27 protein and Ki-67 (Novocastra, UK). The sections for immunohistochemical study were stained using the streptavidin - biotin method. The average percentage of cells stained positively for all cases for p27 and Ki-67 was 22.1% (SD=29.2) and 6.0% (SD=8.8) respectively. There was no statistically significant difference between Ki-67 or p27 expression in abdominal and extra-abdominal location. Analysis of p27 and Ki-67 expression levels might indicate that low proliferating activity of desmoid fibroblasts is connected with another mechanism than the one, in which p27 takes part.

[The synchroneous tumors of different histopathology in the parotid salivary gland]. / Synchroniczne wystepowanie nowotworów o roznej histopatologii w obrebie slinianki przyusznej.

Ipsilateral salivary gland tumors of different histological types are very rare. Out of 196 parotidectomies performed (from 03. 2001 to 12. 2005), in 6 (3.06%) cases synchronous tumors of different type has been found in pathologic specimens. In 5 cases pleomorphic adenoma was one of synchronous tumor--in 2 cases with adenocarcinoma and in single cases with salivary duct carcinoma, adenolymphoma, and myoepithelioma. In one case, the adenolymphoma was synchronous with carcinoma planoepitheliale metastaticum from the primary in the skin post auricular area (late metastasis). Following the review of literature concerning the problem, two concepts has been critically discussed--the real synchronous occurrence of two different tumors, and transformation of benign tumor of salivary neoplasm to its malignant form.

[Histopathological diagnosis of thyroid cancer in a multicenter trial]. / Badanie wieloosrodkowe rozpoznan raka tarczycy.

INTRODUCTION: In the front of the problems related to the differentiation between benign and malignant thyroid tumors we decided to perform a multicentre study in order to validate diagnoses of malignant thyroid tumors and assess the inter-observer variability. MATERIAL AND METHODS: Material included 690 cases of malignant and benign thyroid lesions with primary histopathology established in 1985-1999. These cases were selected to multicentre study. The studies were sent from centres which agreed to participate in the project and than coded in the independent centre--Department of Nuclear Medicine and Endocrine Oncology. 40 pathologists from 25 centres provided their diagnoses which were compared with the reference ones. RESULTS: 10 547 diagnoses were evaluated, both on their accuracy of the distinction between malignant and benign lesions and on their accuracy of cancer histotype definition. The reference diagnosis was made by an agreement between four expert pathologists (D.L., S.S., J.S. and A.K.). The participants diagnosed 21% of cases differently than experts. Concerning the diagnosis of cancer histotype, the difference between participants diagnosis and the reference one was even higher. The best concordance was achieved in the diagnosis of papillary thyroid cancer, however, on the cost of cancer overdiagnosis by some participants. Follicular cancer was diagnosed accurately only in 75.4% of cases. CONCLUSION: The study documents a high inter-observer variability of thyroid cancer diagnosis and confirms the lesser accuracy of diagnosis of follicular cancer.

Gastrointestinal stromal tumors. A multicenter experience.

The report presents 200 cases of gastrointestinal stromal tumors (GIST). The material originated from six diagnostic centers in Poland and was reclassified according to the current criteria. Among lesions other than GISTs, 14 were identified as smooth muscle tumors and seven as neural tumors. GISTs were located in the stomach (51-63.3% of the investigated series), small intestine (27.4-33.8%), colon (approximately 4.5%), abdominal cavity, i.e. in the peritoneum and omentum (6%), and in the retroperitoneal space (2.5%). A slight predominance of women was noted (53-56%). The age of the patients ranged between 14 and 93 years of life, with the mean age of 62.4 years. Individuals younger than 45 years of age accounted for 10% of the group. In ten patients (five of them less than 45 years of life), multiple tumors were detected, their number ranging from two to less than 20; these individuals constituted 5% of the entire series. Moderately and highly aggressive tumors predominated. In the series, when multiple tumors were excluded, a total of 24 epithelioid GISTs (12%) were observed; of this number, 13 were situated in the stomach, six--in the small intestine, two--in the abdominal cavity and another two in the retroperitoneal space. Synchronic tumors observed in patients with GISTs were seen in seven patients, including an adenocarcinoma of the colon, two adenocarcinomas of the stomach, a carcinoid tumor of the small intestine, a pheochromocytoma of the retroperitoneal space, an anaplastic lymphoma and a disseminated squamous cell carcinoma. In immunohistochemical reactions (CD117, CD34, SMA, S-100, DES), attention was focused on the immunoreactivity of small GISTs, below 2 cm in size, and of multiple tumors. Immunohistochemical reactions were equally differentiated as to their presence and intensity in small tumors and in highly aggressive lesions above 5-10 cm in size. In multiple GISTs, immunohistochemical tests strongly indicated the heterogeneity of neoplastic cells, which, nevertheless, showed no consistent association with the location of the tumor, its aggressiveness, cellular structure or a tendency to form multiple foci.

Analysis of cyclin D1 and retinoblastoma protein immunoreactivity in follicular thyroid tumors.

Protein products of cyclin D1 and retinoblastoma (Rb) genes play crucial roles in regulation of G1/S transition in the cell cycle. In this study we analyzed, using immunohistochemical methods, the expression of cyclin D1 and Rb proteins in material from medical archives (12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 nodular goiter cases). A positive nuclear reaction for cyclin D1 was observed in 83.3% (10/12) of the follicular carcinomas, in 96.5% (55/57) of the follicular adenomas and in 23.5% (4/17) of nodular goiters. Overexpression of cyclin Dl (more than 50% of positively staining cells) was noted in 25% (3/12) of the follicular carcinomas and in 22.8% (13/57) of the follicular adenomas. No overexpression of cyclin D1 was noted among nodular goiters. The number of carcinoma cases with cyclin D1 overexpression did not differ statistically in any significant way from the follicular adenoma group (p = 1.000). A positive nuclear reaction for Rb protein was noted in 100% of the follicular carcinomas (12/12), in 96.5% of the follicular adenomas (55/57) and in 47.1% of the cases (8/17) of nodular goiter. Rb protein overexpression (more than 50% of positively staining cells) was found in 83.3% (10/12) of the follicular carcinomas, in 68.4% (39/57) of the follicular adenomas and in 11.8% (2/17) of the nodular goiters. The number of cases with Rb protein overexpression in the follicular carcinoma group did not differ significantly from that in the follicular adenoma group (p = 0.486). A positive correlation was found in the groups studied between the expressions of Rb protein and cyclin D1. However, the correlation was statistically significant only in the nodular goiter group (Rs = 0.567; p = 0.018). In the follicular carcinoma group, that correlation was borderline (Rp = 0.437; p = 0.072) and, in the follicular adenoma group, it was statistically insignificant (Rs = 0.217; p = 0.105). Our results confirm the existence of mutual regulation mechanisms of Rb and cyclin D1 protein expressions, which are observed in cells from various carcinomas.