Uncommon benign lesions of the adrenal glands mimicking sinister pathologies: report of 8 cases.

PURPOSE: To present series of patients with large rare primary lesions of the adrenal glands that were operated in our department. The initial indication for surgery was decided based on their impressive similarity to other more sinister adrenal pathologies. METHODS: The clinical records of the department and histopathology reports, covering the 1986-2015 period were assessed. Rare adrenal pathologies that preoperatively were clinically mimicking other adrenal tumors were included. RESULTS: In total, 8 patients (age range 20-75 years) with rare tumors of the adrenal glands were found. Seven patients had a preoperative indication for adrenalectomy due to the possibility of malignancy. In one patient surgery was undertaken due to the possible diagnosis of adrenal hemorrhagic cyst. Among these patients 4 had a histopathologic diagnosis of hemangiomas, one of a lymphangiomatous cyst and 3 of myelolipomas. CONCLUSION: Rare benign tumors of the adrenal glands can present as very large lesions that can be either diagnosed incidentally or due to atypical symptoms. Though unusual, they should be considered in the differential diagnostic approach of adrenal lesions, because they share common clinical and radiological characteristics with more sinister and frequent lesions such as malignant tumors and also hematomas.

Inferior vena cava obstruction and collateral circulation as unusual manifestations of hepatobiliary cystadenocarcinoma.

BACKGROUND: Hepatobiliary cystadenocarcinoma represents a rare epithelial malignant tumor derived from the intrahepatic bile duct. METHODS: A 71-year-old woman, who had undergone laparoscopic drainage of a cystic lesion of the right hepatic lobe, was misdiagnosed as having hepatic echinococcal disease, and received intracystic infusion of 95% ethanol four years ago. She was admitted to our hospital for further treatment. RESULTS: Physical examination revealed dilated superficial veins across the right abdominal wall. After mapping the direction of blood flow in these vessels, we assumed that this was a sign of inferior vena cava obstruction. Abdominal ultrasound, computed tomography, magnetic resonance imaging combined with magnetic resonance angiography showed a large cystic mass in the right upper quadrant and epigastrium, displacing the adjacent structures, adherent to the inferior vena cava, which was not patent, resulting in dilation of superficial epigastric veins. The patient underwent an exploratory laparotomy. Total excision of the huge mass measuring 16X15 cm was possible under selective vascular exclusion of the liver. Removal of the tumor resulted in immediate restoration of flow in the inferior vena cava. On the basis of the pathology and findings of immunohistochemical analysis, a hepatobiliary cystadenocarcinoma was diagnosed. CONCLUSIONS: In the present case, hepatobiliary cystadenocarcinoma was accompanied by dilated superficial venous collaterals due to inferior vena cava obstruction. Selective vascular exclusion of the liver allowed a safe oncological resection of the tumor.

Clinicopathological features and immunoprofile of 30 cases of Brenner ovarian tumors.

AIM: The aim of this study was to investigate the clinicopathological and immunopathological features of Brenner ovarian tumors. MATERIALS AND METHODS: Thirty cases of Brenner ovarian tumors were examined in our laboratory among 1,680 cases of ovarian tumors, representing 1.5% of all tumors examined. Blocks of paraffin-embedded tumor tissue for all cases were available for additional immunohistochemical stain by a Ventana autoimmunostainer. Moreover, antibodies for Uroplakine III (cellmarque AU-1 clone, 1:25) Chromogen (monosan clone 5H7,1:25) WT1 (novocastra, clone 3F-H2, 1:25) NSE (DAKO, clone BB5/NC/V1-H14, 1:50), CK20 (DAKO, clone Ks20.8, 1:50),CK7 (Zymed 1:25, clone V-TL12/30)were used. RESULTS: The mean age of the patients was 51.4 years ranging from 16 to 82 years. The tumor was unilateral in 28 cases (16/28 in the right ovary and 12/28 in the left ovary) and bilateral in two cases. Twenty-eight cases (93%) were benign and two (7%) were proliferating (borderline) tumors. Seventeen cases (56%) were pure Brenner tumors, measuring from 0.5 to 2.5 cm and 13 cases (44%) were mixed tumors consisting of a Brenner tumor element and a mucinous ovarian tumor (10/13 cases, 53.8%) and a germ cell tumor in 3/13 cases. The largest diameter of the mixed tumors ranged from 7 to 22 cm. The largest area consisting of Brenner elements measured 7 cm. The immunoprofile of Brenner tumor cell was cytokeratine-7 positive (30/30 cases) cytokeratine-20 negative in the Brenner cell element but positive in the mucinous component in 5/7 cases of mixed Brenner tumors, focally WT-1 positive (5/30 cases), NSE negative (0/30 cases) and focally chromogranine positive (6/30 cases), Uroplakin-III positive in 23/30 cases, with faint cytoplasmatic or luminal distribution. In conclusion, Brenner ovarian tumors are unilateral, small and benign neoplasms in their majority and present specific histopathological and immunopathological characteristics and mixed forms with other epithelial and germ cell neoplasms. This could be explained as a form of metaplasia or a diverse histogenesis from surface epithelium and/or the germ cell ovarian component.

Abnormal uterine bleeding as a presentation of metastatic breast disease in a patient with advanced breast cancer.

BACKGROUND: Extragenital carcinomas secondarily involving the uterus are very rare and they usually occur as a manifestation of widespread disease. When the metastases involve the endometrium in a diffuse, permeative pattern, sparing the glands, they may cause problems in the diagnosis. CASE: A case of metastatic carcinoma to the endometrium with a decidua-like pattern is reported. The patient had a history of breast carcinoma and presented with vaginal bleeding. The pathologic findings in the uterine curettings raised the differential diagnosis between metastatic breast carcinoma and non-neoplastic stromal lesions. The presence of nuclear atypia and mitotic activity along with the appropriate immunohistochemical findings revealed the neoplastic nature of the endometrial lesion and confirmed its origin from the breast. CONCLUSION: Unusual uterine bleeding in a patient with breast cancer should alert the gynecologist to the possibility of metastatic breast disease. Furthermore, the metastasis to the uterus and to other organs of the genital tract can be considered as a preterminal event.

Unilateral simultaneous renal oncocytoma and angiomyolipoma: case report.

A rare case of synchronous angiomyolipoma and oncocytoma in the same kidney of a 70 year old man is presented. A left renal mass was found incidentally by ultrasound. Computerized tomography and magnetic resonance imaging revealed a 1,3 cm mass in the mid-portion of the left kidney, whereas on the lower pole of the same kidney, a 3,3 cm mass was also revealed, consistent with angiomyolipoma. A working diagnosis of renal cell carcinoma was made. A radical nephrectomy was performed. Microscopically, the tumor of the lower pole was found to be an angiomyolipoma, whereas the mid-portion tumor was an oncocytoma. Until now, only 16 cases of unilateral simultaneous presence of renal angiomyolipoma and oncocytoma have been reported. Of these cases, all except one were female and three were associated with the tuberous sclerosis complex. It is well worth remarking, that renal oncocytoma overlap with other renal neoplasms, therefore nephrectomy remains the treatment of choice.Renal angiomyolipoma and oncocytoma are uncommon neoplasms and their simultaneous presence in the same kidney is rare. Only 16 cases have been reported until now in the literature. The purpose of this paper is to present an additional case without evidence of tuberous sclerosis.

Mixed acinar-endocrine carcinoma of the pancreas: a case report and review of the literature.

INTRODUCTION: Pancreatic tumors usually display either a ductal, an acinar or an endocrine differentiation. Mixed exocrine and endocrine pancreatic tumors are extremely rare. There have been a few reports of the rare entity of mixed acinar-endocrine carcinoma of the pancreas, where the endocrine cells represent more than 30% of the tumor. We herein describe a case of such a pancreatic tumor in an asymptomatic patient. CASE PRESENTATION: A 74-year-old male patient with no evident clinical symptoms was referred for surgical resection of a large mass located on the pancreatic head, which was confirmed by an abdominal U/S, CT and MRI. FNA of the mass under endoscopic ultrasound guidance showed the cytology specimen to comprise of cells with morphological and immunohistochemical characteristics of endocrine pancreatic neoplasms. The patient underwent a modified Whipple's procedure and his post-operative course was uneventful. Pathological examination of the tumor revealed a mixed acinar-endocrine carcinoma of the pancreas. CONCLUSION: Mixed tumors of the pancreas are extremely rare and their clinical features and pathogenesis remain unclear. The endocrine component seems to influence their prognosis favorably.Therefore, aggressive surgical therapy remains the only well established line of treatment for these tumors. Further accumulation of clinical cases will help clarify the clinical course and the optimal therapy for these unusual tumors.

KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential.

AIM: To study the association of the frequency and pattern of KIT and PDGFRA mutations and clinicopathological factors in a group of patients with gastrointestinal stromal tumors (GIST). METHODS: Thirty patients with GIST were examined. Exons 9, 11, 13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing. RESULTS: KIT or PDGFRA mutations were detected in 21 of the 30 patients (70%). Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant (P < 0.05). Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour (P < 0.003). GISTs with PDGFRA mutations located in stomach showed a mixed cell phenotype and were classified as of very low or low moderate malignant potential. CONCLUSION: Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.

Expression and prognostic significance of cyclin D3 in ovarian adenocarcinomas.

Abnormal expression of cell cycle regulators may contribute to malignant transformation. However, the clinical significance of the expression of cyclin D3 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to address the role of this cell-cycle protein in this tumor. In our study, paraffin-embedded tissue from 109 nonbenign epithelial ovarian tumors, including 17 tumors of low malignant potential and 92 primary adenocarcinomas, was stained immunohistochemically for cyclin D3. Most of the cases had previously been stained for pRb, p21Cip1, p27Kip1, p53, and Ki-67 antigen. Expression of cyclin D3 was correlated with clinicopathologic features, the expression of other cell cycle regulators, and postoperative survival of patients. Cyclin D3 levels were significantly higher in tumors of low malignant potential than in adenocarcinomas (P = 0.0002). In the latter group, cyclin D3 expression decreased with increasing grade (P = 0.0004) and advancing stage (P = 0.0315). Cyclin D3 expression positively correlated with pRb, p21Cip1, and p27Kip1 levels (P = 0.0021; P = 0.0036; P < 0.0001, respectively) and negatively with p53 and Ki-67 (P = 0.0003; P < 0.0001). Absent cyclin D3 expression was an important indicator of poor survival in univariate analysis in the entire cohort (P > 0.00010) and in the platinum-treated patients (P = 0.001) and in multivariate analysis (P = 0.044). Our results demonstrate that absent or decreased cyclin D3 expression is adversely related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is combined with a better prognosis, suggesting that cyclin D3 may have a biological role distinct from that of other G1 cyclins which is possibly regulated through interaction with other cell cycle genes.

KIT-negative gastrointestinal stromal tumors with a long term follow-up: a new subgroup does exist.

AIM: To investigate the incidence of KIT immunohistochemical staining in (GI) stromal tumors (GISTs), and to analyze the clinical manifestations of the tumors and prognostic indicators. METHODS: We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT (CD117 antigen), CD34, SMA, desmin, S-100, NSE, PCNA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors. RESULTS: Fifteen tumors (30%) were negative in KIT staining. A significant association was observed between gender (male patients: 14/15) and KIT-negative staining (P = 0.003).The patients's mean age was 56.6 years. Tumors developed in stomach (n = 8), small intestine (n = 5), large intestine (n = 1) and oesophagus (n = 1). The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF (mean: 3.4) and 73% of tumors showed no necrosis. The majority of the tumors (67%) had dual or epithelioid differentiation. Tumors were classified as very low or low risk (n = 7), intermediate risk (n = 5), and high risk (n = 3) groups. Twelve (80%) patients were alive without evidence of residual tumor for an average period of 40.25 mo (12-82 mo); three patients developed metastatic disease to the liver and eventually died within 2-12 mo (median survival: 8.6 mo). CONCLUSION: A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations.

Malignant potential of intrahepatic biliary papillomatosis: a case report and review of the literature.

BACKGROUND: Biliary papillomatosis (BP) is a rare disease entity with a strong malignant potential. It is characterized by multiple papillary adenomas involving both the intrahepatic and extrahepatic biliary tree. BP was considered in the past to be a disease with low malignant potential. However, a current review of the English literature revealed a high rate of malignant occurrence of approximately 41% and histological analysis along with the expression pattern of mucin core proteins (MUC) and mucin carbohydrate antigens suggests that BP is a borderline or low grade malignant neoplasm with a high malignant potential. CASE PRESENTATION: A 68 year-old male patient was referred to our hospital due to the presence of sudden right upper quadrant abdominal pain, nausea and dark urine. Imaging workup demonstrated dilatation of the left hepatic duct without the presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were carried out and histological analysis revealed a moderately to poorly differentiated carcinoma of the left hepatic duct in the background of biliary papillomatosis. Postoperative course was uneventful. Unfortunately, two years after initial diagnosis the patient rapidly deteriorated and died from multiple pulmonary secondary deposits. CONCLUSION: BP should not be considered to be a benign disease. The clinical behavior, the high recurrence rate and the even higher malignant transformation occurrence, as well as the presence of carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn antigens) strongly support that BP is a low-grade neoplasm with high malignant potential.