Diagnostic Pathology - Latest Articles

Sub-typing of renal cell tumours; contribution of ancillary techniques

Dinesh Pradhan — 2009-06-28T00:00:00Z

Background: Adult renal epithelial neoplasms are a heterogeneous group with varying prognosis and outcome requiring sub-classification. Methods: Cases of renal cell carcinoma (RCC) in a 10 years period were analyzed with regard to the clinical features and histology. Sections were reviewed by four pathologists and the discordant cases were resolved with the help of Hale's colloidal iron stain, vimentin, CK 7, and vinculin immunostains and electron microscopy. Results: Amongst the total 278 cases, clear cell renal cell carcinoma was the commonest tumor with 74.8% cases, followed by papillary RCC 12.2%, chromophobe RCC 7.9%, oncocytoma 1.8%, and one case of collecting duct RCC. Eight cases were of sarcomatoid renal cell carcinoma. In 28/278 cases, diagnoses varied amongst the four pathologists and the discordance was resolved by Hale's colloidal iron stain, CK7 immunostain and electron microscpy. Vimentin and vinculin did not contribute much in differentiating subtypes of renal cell carcinomas. Relative incidence of sub-types of RCCs was compared with other series Conclusion: To accurately subclassify renal cell carcinomas, simple ancillary techniques would possibly resolve all difficult cases. The relative incidence of sub-types of renal cell carcinoma is relatively consistent the world over. However, in India, RCCs afflict the patients two decades earlier.

Which urine marker test provides more diagnostic value in conjunction with standard cytology- ImmunoCyt/uCyt+ or Cytokeratin 20 expression

Isin Soyuer — 2009-06-26T00:00:00Z

Background: Because of the poor sensitivity of urinary cytological findings for the diagnosis of especially low grade urinary bladder carcinoma, new molecular diagnostic methods have been proposed. We decided to verify the ImmunoCyt/uCyt+ (UCyt+TM) test and cytology combination and cytokeratin 20 (CK20) and cytology combination in urine as possible diagnostic and monitoring tool for bladder cancer. Methods: Evaluation of CK20 expression and UCyt+TM was performed in urine of 90 patients of which 54 with bladder cancer with primary/recurrent diagnosis (low grade urothelial carcinoma (LGUC)=23/8 patients, high grade urothelial carcinoma (HGUC)=18/5 patients), and 36 patients as control; except of neoplastic bladder disease patients. For the evaluation of the three tests, CK20 and UCyt+TM tests were combined with urine cytology and compared with each other. Results: The overall sensitivity detected for each tumor marker was as follows: for urine cytology was 75.9% and UCyt+TM was 83.3%, for CK20 70.4%, while the specificity was 66.7% for urine cytology and 86.1% for UCyt+TM and 83.3% for CK20. The sensitivity of cytology and UCyt+TM combination was higher (88.9%) than the sensitivity cytology and CK20 combination (77.8%). The simultaneous use of the three markers, sensitivity was reaching 92.5%. Conclusions: The UCyt+TM test and CK20 expression are valid tools for the performance of adjunctive analyses with conventional cytologic examination.

Mobile cell-phones (M-phones) in telemicroscopy: increasing connectivity of isolated laboratories

Livia Bellina — 2009-06-19T00:00:00Z

Background: The development of modern information telecommunication (ITC) technology and its use in telemedicine plays an increasingly important role in facilitating access to some diagnostic services even to people living in the most remote areas. However, physical and economical constraints in the access to broad band data-transmission network, still represent a considerable obstacle to the transmission of images for the purpose of tele-pathology. Methods: Indifferently using m-phones of different brands, and a variety of microscopic preparations, images were taken without the use of any adaptor simply approaching the lens of the mobile cell phone camera to the ocular of common optical microscopes, and subsequently sent via Multimedia Messaging Services (MMS) to distant reference centres for tele-diagnosis. Access to MMS service was reviewed with specific reference to the African information communication technology (ICT) market. Results: Images of any pathologic preparation could be captured and sent over the mobile phone with an MMS, without being limited by appropriate access to the internet for transmission (i.e. access to broad-band services). The quality of the image was not influenced by the brand or model of the mobile-phone used, but only by its digital resolution, with any resolution above 0.8 megapixel resulting in images sufficient for diagnosis.Access to MMS services is increasingly reaching remote disadvantaged areas. Current penetration of the service in Africa was mapped appearing already available in almost every country, with penetration index varying from 1.5% to 92.2%. Conclusions: The use of otherwise already widely available technologies, without any need for adaptors or otherwise additional technology, could significantly increase opportunities and quality diagnostics while lowering costs and considerably increasing connectivity between most isolated laboratories and distant reference center.

Expression of p-AKT characterizes adenoid cystic carcinomas of head and neck with a higher risk for tumor relapses

Hans-Ullrich Volker — 2009-06-19T00:00:00Z

Background: Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies. Methods: Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1. Proliferation was investigated by staining with Ki67. The tumors were located at the major or minor salivary glands. Only the typical cribriform subtype was investigated. The initial tumor stage was pT1 or pT2. Results: Expression of p-AKT was significantly (P = 0.036) associated with a higher relapse risk in multivariate analysis. Low expression of M2PK was non-significantly (P = 0.065) predictive for a higher risk. TKTL-1 and GLUT-1 were expressed in the majority of cases, albeit not associated with relapse risk. Conclusion: Adenoid cystic carcinomas positive for p-AKT show a higher relapse risk. However, other parameters of glucose metabolism investigated here or proliferation (Ki67) were not predictive in this entity. Our findings demonstrate a possible background for therapeutic approaches targeting the inhibition of PI3K/AKT pathway.

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

Henry Armah — 2009-06-14T00:00:00Z

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

A case of lipomatous pleomorphic adenoma in the parotid gland

Takeshi Kondo — 2009-06-04T00:00:00Z

IntroductionPleomorphic adenoma is the most common benign neoplasm of the salivary glands. Extensive lipomatous involvement of the tumor is, however, a very rare finding.Case report:Herein, a rare case of lipomatous pleomorphic adenoma arising in the parotid gland of a 14-year-old Japanese woman is presented. Conclusion: This is the sixth case of lipomatous pleomorphic adenoma in the English literature. Recognition of this rare subtype of pleomorphic adenoma is important for clinical diagnosis and management. On CT scan, it may not be detected possibly due to the extensive fatty component.

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

Henry Armah — 2009-05-18T00:00:00Z

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.Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring during pregnancy with a novel translocation involving chromosome 19 followed an indolent clinical course.

Immunohistochemical localization of mdm-2, p27 Kip1 and bcl-2 in Warthin's tumor of the parotid gland.

Ehab Abd Elhamid — 2009-05-16T00:00:00Z

Background: Warthin's tumor is a benign monomorphic adenoma with unclear origin that almost occur exclusively in the parotid gland. Etiology of Warthin's tumor as well as its malignant potential are still unclear. Therefore immunohistochemical assessment of Warthin's tumor may be useful to detect its origin or its malignant transformation potential.Aims and objectivesThe present study aims to investigate the immunohistochemical expression of murine double minute-2 (mdm-2), p27Kip1 and B cell lymphoma-2 (bcl-2) in Warthin's tumor of parotid gland and also to clarify the role of these proteins in the behavior of that tumor. Methods: Twenty paraffin blocks of cases previously diagnosed as Warthin's tumor were collected for immunohistochemical staining with primary antibodies against mdm-2, p27Kip1 and bcl-2 using streptavidin-biotin immunoperoxidase staining system. Results: All cases showed immunopositivity for mdm-2 and p27Kip1 while 18/20 showed bcl-2 immunopositivity. Both layers of the neoplastic epithelial cells that line the cystic spaces showed immunopositivity with all antibodies used. Goblet cells were mdm-2 immunonegative while myoepithelial cells were p27Kip-1 immunonegative. Areas of epithelial proliferation that formed buds were p27Kip-1 and bcl-2 immunopositive. Conclusion: Mdm-2 played a tumor-suppressor role that might be implicated with the benign behavior of Warthin's tumor. The mutual expression of both p27Kip1 and bcl-2 suggested a protective role of these slowly proliferating cells from apoptosis to maintain their survival and elevated bcl-2 expression offers a significant protection against p27Kip1-mediated apoptosis.

PAS staining of bronchoalveolar lavage cells for differential diagnosis of interstital lung disease

Hans Hauber — 2009-04-23T00:00:00Z

Bronchoalveolar lavage (BAL) is a useful diagnostic tool in interstitial lunge diseases (ILD). However, differential cell counts are often non specific and immunocytochemistry is time consuming. Staining of glyoproteins by periodic acid Schiff (PAS) reaction may help in discriminating different forms of ILD. In addition, PAS staining is easy to perform. BAL cells from patients with idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 9), and extrinsic allergic alveolitis (EAA) (n = 2) were investigated. Cytospins from BAL cells were made and cells were stained using Hemacolor quick stain and PAS staining. Lymphocytic alveolitis was found in sarcoidosis and EAA whereas in IPF both lymphocytes and neutrophils were increased. PAS positive cells were significantly decreased in EAA compared to IPF and sarcoidosis (25.5% ± 0.7% vs 59.8% ± 25.1% and 64.0% ± 19.7%, respectively) (P < 0.05). No significant correlation between PAS positive cells and inflammatory cells was observed. These results suggest that PAS staining of BAL cells may provide additional information in the differential diagnosis of ILD. Further studies ware warranted to evaluate PAS staining in larger numbers of BAL from patients with ILD.

Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes

Bernhard Schaaf — 2009-04-16T00:00:00Z

Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4.Protein expression of CD14, TLR2 and TLR4 on blood monocytes was examined using flow cytometry from 29 patients with sepsis and 14 healthy controls. In addition LPS stimulated TNF-α and IL-10 production was studied in a 24 hour whole blood assay.We found an increased expression of CD14, TLR2 and TLR4 in patients with sepsis compared to controls (p < 0.01). In patients with sepsis, death was associated with significant lower CD14 and TLR2 expression at admission (CD14: 25.7 +- 19.1 vs 39.1 +- 17.3 mean fluorescence intensity [MFI], p = 0.02; TLR2: 21.8 +- 9.4 vs. 30.9 +- 9.6, p = 0.01). At 72 hours the TLR2 expression on monocytes was associated with the IL-10 inducibility after LPS stimulation (r = 0.52, p = 0.02) and the CD14 expression with the IL-6, IL-10 and TNF inducibility.We conclude that septic patients are characterized by an increased expression of CD14, TLR2 and TLR4 on monocytes compared to controls. Death is associated with downregulation of TLR2 and CD14 expression on monocytes correlating with reduced cytokine inducibility. We suggest that CD14 and TLR2 are a key factor in monocyte hyporesponsibility during severe sepsis.