Atypical adenomatous hyperplasia (adenosis) of the prostate: a case report with review of the literature

A 62-year-old male presented with symptoms of urinary obstruction and elevated serum prostate-specific antigen level of 3.61 ng/mL. Prostate needle biopsies showed benign prostatic tissue with a focus of crowded glands with minimal cytological atypia, fairly well-circumscribed with infiltrative appearance of glands at the edges. This focus had both small and larger glands with similar histological features. This focus was strongly positive for alpha-methylacyl-coenzyme A-racemase (AMACR), but showed scattered patchy staining with basal cell markers (p63 and CK903/34βE12). Hence, the final histologic diagnosis was benign prostatic tissue with a focus of florid adenosis. Two subsequent follow-up prostate needle biopsies performed six and 12 months later both showed benign prostatic tissue with atrophic changes. This case highlights the utility of these three immunostains (AMACR, p63 and CK903/34βE12) in the accurate diagnosis of adenosis of the prostate on needle biopsy, and avoiding its misinterpretation as prostate adenocarcinoma

Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late renal and pulmonary metastases: a case report with review of the literature

<p>Abstract</p> <p>Background</p> <p>Perivascular epithelioid cell tumor (PEComa), other than angiomyolipoma (AML), clear cell sugar tumor (CCST), and lymphangioleiomyomatosis (LAM), is a very rare mesenchymal tumor with an unpredictable natural history. The uterus is the most prevalent reported site of involvement of PEComa-not otherwise specified (PEComa-NOS). To the best of our knowledge, about 100 PEComa-NOS have been reported in the English Language medical literature, of which 38 were uterine PEComa-NOS. These reported cases of uterine PEComa-NOS have usually shown clinically benign behavior, but 13 tumors, three of them associated with tuberous sclerosis complex (TSC), exhibited local aggressive behavior and four of them showed distant metastases.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old woman, who presented with renal and pulmonary lesions seven years after the initial diagnosis of uterine leiomyosarcoma. Left nephrectomy and right middle lobe wedge resection were performed. Histological and immunohistochemical analysis of the renal and pulmonary lesions, in addition to retrospective re-evaluation of the previous uterine tumor, led to the final diagnosis of malignant uterine PEComa with late renal and pulmonary metastases. All three lesions had the typical histological appearance of PEComa-NOS showing a biphasic growth pattern with continuous transition between spindle cells and epithelioid cells, often arranged around vascular spaces. Immunohistochemically, the tumor cells of both phenotypes in all three lesions stained for melanocytic (HMB-45 and Melan-A/MART-1) and myoid (desmin, smooth muscle actin, and muscle-specific actin/all muscle actin/HHF-35) markers.</p> <p>Conclusion</p> <p>The findings indicate that despite the small number of reported cases, PEComas-NOS should be considered tumors of uncertain malignant potential, and metastases to other organs might become evident even several years after the primary diagnosis.</p

Altered Lipid Composition and Enhanced Lipid Production in Green Microalga by Introduction of Brassica Diacylglycerol Acyltransferase 2

Higher lipid biosynthesis and accumulation are important to achieve economic viability of biofuel production via microalgae. To enhance lipid content, Chlamydomonas reinhardtii was genetically engineered with a key enzyme diacylglycerol acyltransferase (BnDGAT2) from Brassica napus,responsible for neutral lipid biosynthesis. The transformed colonies harbouring aph7 gene, screened on hygromycin-supplemented medium, achieved transformation frequency of ~120 ± 10 colonies/1 × 106cells. Transgene integration and expression were confirmed by PCR, Southern blots, staining lipid droplets, proteins and spectro-fluorometric analysis of Nile red-stained cells. The neutral lipid is a major class (over 80% of total lipids) and most significant requirement for biodiesel production; this was remarkably higher in the transformed alga than the untransformed control. The levels of saturated fatty acids in the transformed alga decreased to about 7% while unsaturated fatty acids increased proportionately when compared to wild type cells. Polyunsaturated fatty acids, especially α-linolenic acid, an essential omega-3 fatty acid, were enhanced up to 12% in the transformed line. Nile red staining confirmed formation of a large number of lipid globules in the transformed alga. Evaluation of long-term stability and vitality of the transgenic alga revealed that cryopreservation produced significantly higher quantity of lipid than those maintained continuously over 128 generations on solid medium. The overexpression of BnDGAT2significantly altered the fatty acids profile in the transformed alga. Results of this study offer a valuable strategy of genetic manipulation for enhancing polyunsaturated fatty acids and neutral lipids for biofuel production in algae

Synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney: a unique case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Malignant transformation of mature cystic teratoma is a rare complication. While any of the constituent tissues of a teratoma has the potential to undergo malignant transformation, squamous cell carcinoma is the most commonly associated malignancy. Renal carcinoid tumors are rare and frequently associated with horseshoe kidney and renal teratoma. Renal teratoma rarely presents together with carcinoid tumor or adenocarcinoma. To the best of our knowledge, there has never been a report of renal teratoma coexisting with both carcinoid tumor and adenocarcinoma.</p> <p>Methods</p> <p>Here, we present a unique and first case of synchronous primary carcinoid tumor and moderately differentiated adenocarcinoma arising within mature cystic teratoma of horseshoe kidney in a 50-year-old female. Lumbar spine X-ray, done for her complaint of progressive chronic low back pain, accidentally found a large calcification overlying the lower pole of the right kidney. Further radiologic studies revealed horseshoe kidney and a large multiseptated cystic lesion immediately anterior to the right renal pelvis with central calcification and peripheral enhancement. She underwent right partial nephrectomy.</p> <p>Results</p> <p>Macroscopically, the encapsulated complex solid and multiloculated cystic tumor with large calcification, focal thickened walls and filled with yellow-tan gelatinous material. Microscopically, the tumor showed coexistent mature cystic teratoma, moderately differentiated adenocarcinoma and carcinoid tumor. Immunohistochemically, alpha-methylacyl-coenzyme A-racemase, calretinin, CD10 and thyroid transcription factor-1 were negative in all the three components of the tumor. The teratomatous cysts lined by ciliated epithelium showed strong staining for cytokeratin 7 and pancytokeratin, and those lined by colonic-like epithelium showed strong staining for CDX2, cytokeratin 20 and pancytokeratin, but both were negative for calretinin. Additionally, the teratomatous cyst wall showed strong staining for smooth muscle actin, and weak staining for carbonic anhydrase IX, CD99, chromogranin and synaptophysin. The adenocarcinoma component was strongly positive for cytokeratin 7 and pancytokeratin, weakly positive for synaptophysin and CD56, and negative for carbonic anhydrase IX, CD99, CDX2, chromogranin, cytokeratin 20 and smooth muscle actin. The carcinoid tumor component was strongly positive for CD56, chromogranin and synaptophysin, weakly positive for pancytokeratin, and negative for carbonic anhydrase IX, CD99, CDX2, cytokeratin 7, cytokeratin 20 and smooth muscle actin. She received no adjuvant therapy and is alive without evidence of disease six months after diagnosis and surgery.</p> <p>Conclusion</p> <p>This unique and first case herein presented with synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney emphasizes the need for thorough sectioning and entire submission for histologic evaluation of mature cystic teratomas, in order to avoid missing multiple additional histogenetically distinct neoplasms.</p

Tubular adenoma with high-grade dysplasia in the ileal segment 34 years after augmentation ileocystoplasty: report of a first case

Neoplasms of the urinary bladder following augmentation ileocystoplasty are rare. We present the case of a 39-year-old male with a tubular adenoma with high-grade dysplasia in the ileal segment 34 years after augmentation ileocystoplasty to enlarge a post-chemoradiation-induced shrunken bladder. He presented with gross hematuria. Cystoscopy revealed a papillary tumor at the site of ileovesical anastomosis, and transurethral resection was performed. Histologic examination revealed a tubular adenoma with high-grade dysplasia. There are only two previous reports of tubulovillous adenoma in ileal segment after ileocystoplasty, both without high-grade dysplasia. Our observation supports the hypothesis that an ileal neobladder may undergo all the morphologic and molecular changes observed in the development of gastrointestinal adenocarcinoma. Therefore, patients who had an ileal neobladder created should be closely followed

Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present

Overcoming scale-up challenges for a First-In-Human (FIH) antibody production process at the 2000L scale: Successful optimization of bioreactor equipment and harvest conditions to improve process performance and product yield

During the development and scale-up of a FIH fed-batch cell culture process, we have encountered two major challenges that impacted culture performance and harvest process yield significantly. The first challenge relates to the oxygen requirement for this particular process, where a higher oxygen demand was observed compared to our platform processes. The high oxygen demand is met by increasing agitation and sparging of air and oxygen in bioreactors, but also negatively impacted cell health due to higher gas entrance velocities (GEV) from the higher sparging rate. The observation is exemplified in the manufacturing scale which significantly impacted cell culture performance and antibody production. Further exacerbating this issue, many sparger holes were later found to be plugged leading to a theoretical GEV as high as 300 m/s. Extensive troubleshooting studies were carried out at small scale to confirm the impact of high GEV on this antibody production process and led to the re-design of the sparger for the manufacturing scale. Once implemented, the new sparger successfully mitigated the issue. The second challenge was relating to harvest operation, where the final membrane filter was clogged at the manufacturing scale. Studies were performed at the pilot scale to evaluate different solutions including increasing depth filter area, testing different types of the final filter, and changing the chase buffer at the manufacturing scale. In the end, successful implementation of the new sparger design and optimized harvest conditions led to comparable process performance between the manufacturing scale and the pilot scale. The final process resulted not only in an increase in the overall product yield, but also prevented the need of filter change-outs during the harvest operation, therefore, significantly improving manufacturing ease