Zhanyong Bing

CDX2 Expression in Yolk Sac Component of Testicular Germ Cell Tumors

CDX2 has been detected in the majority of colorectal adenocarcinoma cases and may be useful in determining the sites of origin of tumors. In this study, the authors evaluated CDX2 expression in germ cell tumors (GCTs) by immunohistochemistry. Forty cases of testicular GCTs and 8 cases of metastatic GCTs were retrieved for study. In the 40 cases of testicular GCTs, 13 were pure seminomas and 27 mixed GCTs. Yolk sac tumor (YST) was identified by morphology and glypican 3 staining in 20 testicular mixed GCTs. Of these 20 cases, 8 cases showed 1+ positivity for CDX2. Other primitive components of GCTs were negative. For the 6 cases of metastatic mixed GCT with YST, 4 cases were positive, 2+ in 2 cases and 1+ in 2 cases. The positivity of CDX2 in GCTs warrants including YST in the differential diagnosis of adenocarcinoma of unknown origin.

Adult type granulosa cell tumor in adult testis: report of a case and review of the literature

Granulosa cell tumors can be classified into juvenile and adult types and more commonly occur in ovaries. Adult testicular granulosa cell tumors are extremely rare and only 29 cases of adult type have previously been reported. We report here a 28-year old Caucasian man with a left testicular adult type granulosa cell tumor. The tumor measured 2.6×2.6×2.5 cm and was mitotically active (10/10 HPF). Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin, and negative for epithelial membrane antigen, cytokeratins, synaptophysin, HMB-45, OCT-4, placental-like alkaline phosphatase and lymphoid markers. The reported granulosa cell tumors in adult testis were briefly reviewed.

A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study.

The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was composed of sheets of medium-to-large cells with foamy and reticulated cytoplasm and small-to-medium sized nuclei with variably prominent nucleoli. Oil red O stain showed abundant intracellular lipid. Periodic Acid-Schiff stain confirmed the presence of abundant glycogen deposition. Immunohistochemically the tumor cells were positive for Hep Par1, negative for epithelial membrane antigen, steroidogenic factor-1, HMB45, melan A, CK7 and CK20. Electron microscopy study was performed, which was first done in a clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without elevation of liver function tests. Ultrastructural evaluation of the clear cells showed scarce cellular organelles, cytoplasmic lipid vacuoles and swollen mitochondria.

p53 in Pure Epithelioid PEComa An Immunohistochemistry Study and Gene Mutation Analysis

Pure epithelioid PEComa (PEP; so-called epithelioid angiomyolipoma) is rare and is more often associated with aggressive behaviors. The pathogenesis of PEP has been poorly understood. The authors studied p53 expression and gene mutation in PEPs by immunohistochemistry, single-strand conformation polymorphism, and direct sequencing in paraffin material from 8 PEPs. A group of classic angiomyolipomas (AMLs) were also analyzed for comparison. Five PEPs were from kidneys and 1 each from the heart, the liver, and the uterus. PEPs showed much stronger p53 nuclear staining (Allred score 6.4 ± 2.5) than the classic AML (2.3 ± 2.9) (P < .01). There was no p53 single-strand conformation polymorphism identified in either the PEPs or the 8 classic AMLs. p53 mutation analyses by direct sequencing of exons 5 to 9 showed 4 mutations in 3 of 8 PEPs but none in any of the 8 classic AMLs. The mutations included 2 missense mutations in a hepatic PEComa and 2 silent mutations in 2 renal PEPs. Both the missense mutations in the hepatic PEComa involved the exon 5, one involving codon 165, with change from CAG to CAC (coding amino acid changed from glutamine to histidine), and the other involving codon 182, with change from TGC to TAC (coding amino acid changed from cysteine to tyrosine). The finding of stronger p53 expression and mutations in epithelioid angiomyolipomas might have contributed to their less predictable behavior. However, the abnormal p53 expression cannot be entirely explained by p53 mutations in the exons examined in the PEPs.

Expression of parafibromin in major renal cell tumors

Parafibromin, encoded by HRPT2 gene, is a recently identified tumor suppressor. Complete and partial loss of its expression have been observed in hyperparathyroidism-jaw tumor (HPT-JT), parathyroid carcinoma, breast carcinoma, lung carcinoma, gastric and colorectal carcinoma. However, little has been known about its expression in renal tumors. In order to study the expression of parafibromin in a series of the 4 major renal cell tumors - clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), chromophobe renal cell carcinoma (chRCC) and oncocytoma, one hundred thirty nine renal tumors including 61 ccRCCs, 37 pRCCs, 22 chRCCs and 19 oncocytomas were retrieved and used for the construction of renal tissue microarrays (TMAs). The expression of parafibromin was detected by immunohistochemical method on the constructed TMAs. Positive parafibromin stains are seen in 4 out of 61 ccRCCs (7%), 7 out of 37 pRCCs (19%), 12 out of 23 chRCCs (52%) and all 19 oncocytomas (100%). Parafibromin expression varies significantly (P<8.8×10−16) among the four major renal cell tumors and were correlated closely with tumor types. No correlation of parafibromin expression with tumor staging in ccRCCs, pRCCs and chRCCs, and Fuhrman nuclear grading in ccRCCs and pRCCs was seen. In summary, parafibromin expression was strongly correlated with tumor types, which may suggest that it plays a role in the tumorigenesis in renal cell tumors.

Useful immunohistochemical panel for differentiating clear cell papillary renal cell carcinoma from its mimics

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described low-grade renal cell tumor. In this study, we investigated the expression of paired box 8 (PAX-8), carbonic anhydrase IX (CA IX), CK7, and α-methylacyl-CoA-racemase (AMACR) in this tumor by immunohistochemistry in a group of 20 cases of CCPRCC. Clear cell papillary renal cell carcinoma showed diffuse (70%) or intermediate (30%) nuclear positivity for PAX-8 in each case, with predominantly moderate intensity (50%). Ninety percent of the cases showed some degree of cytoplasmic staining for CA IX, predominantly with moderate intensity (50%). In addition, each case of CCPRCC also showed diffuse membranous staining for CK7. Most CCPRCCs (95%) were negative for AMACR. PAX-8, CA IX, CK7, and AMACR comprise a concise panel for distinguishing CCPRCC from its mimics. PAX-8 positivity helps to confirm the renal origin of this tumor. Positivity for CA IX and CK7 differentiate CCPRCC from conventional clear cell renal cell carcinoma, which is usually CA IX positive while CK7 negative. The CK7-positive and AMACR-negative pattern seen in CCPRCC differentiates it from papillary renal cell carcinoma, which is usually positive for both AMACR and CK7.

Cytoplasmic Overexpression of Wt-1 in Gastrointestinal Stromal Tumor and Other Soft Tissue Tumors

The Wilms tumor 1 (WT-1) is a zinc finger transcription factor essential for the development of the kidneys and gonads. Alterations in the WT-1 gene were observed in several tumor types. Depending on the tumor types, WT-1 might function as a tumor suppressor or as a survival factor. WT-1 immunoreactivity in gastrointestinal stromal tumor (GIST) was currently not known. We, therefore, investigated the expression of WT-1 in GIST in comparison to other soft tissue tumors by immunohistochemistry and Western blot analysis. We found that all 28 cases (100%) of GIST are positive for WT-1, diffusely (>75%, 3+) in 13 (46.4%) cases, moderately (26% to 75%, 2+) in 13 (46.4%) cases, and focally (5% to 25%, 1+) in 2 (7.2%) cases. The staining intensity is usually strong. The staining pattern is predominantly cytoplasmic with rare scattered nuclear staining. Similar but less extensive cytoplasmic WT-1 immunoreactivity was detected in 16 of 25 (64%) uterine leiomyosarcoma and 14 of 24 (58.3%) soft tissue leiomyosarcoma. Rare scattered nuclear staining was also seen in uterine leiomyosarcoma and soft tissue leiomyosarcoma, which showed positive cytoplasmic WT-1 reactivity. Only 1 of the 10 solitary fibrous tumors showed weak cytoplasmic WT-1 positivity (10%). No WT-1 staining was detected in 6 cases of fibromatosis. The significance of cytoplasmic expression of WT-1 in GIST and some smooth muscle tumors is unclear and warrant further investigation. The potential roles of WT-1 in the diagnosis and treatment of GIST were discussed.

SALL4 and SF-1 Are Sensitive and Specific Markers for Distinguishing Granulosa Cell Tumors From Yolk Sac Tumors

Granulosa cell tumors are classified as juvenile and adult types. They may be misinterpreted as a yolk sac tumor when they exhibit a “reticular” growth pattern and contain prominent mitotic activity. In this study, the authors performed immunohistochemical stains for SALL4 and steroidogenic factor-1 (SF-1) on 27 cases of yolk sac tumors and 24 granulosa cell tumors. Nuclear stains for both antibodies were considered as positive and the intensity of staining was graded as negative, weak, moderate, and strong. All the yolk sac tumors were positive for SALL4 (100%) with moderate to strong grade staining and negative for SF-1 (100%). In contrast, all the granulosa cell tumors were positive for SF-1 (85% moderate to strong grade staining and 15% weak staining) and negative for SALL4 (100%). The difference was significant (P < .01, Student’s t test). This result indicates that these 2 markers could be used to distinguish these 2 tumors in a difficult situation.

Immunohistochemical Studies of Metastatic Germ-Cell Tumors in Retroperitoneal Dissection Specimens A Sensitive and Specific Panel

Germ-cell tumors (GCTs) are the most common malignancies in adolescent and young men. These tumors are highly treatable, even at an advanced stage; therefore, accurate diagnosis is imperative. In this study, we evaluated immunohistochemical stains for SALL4, NANOG, glypican-3 (GPC3), D2-40, and CD30 with adequate control in retroperitoneal dissection specimens under the same laboratory conditions. The study groups included 31 cases of metastatic testicular GCTs with the following components: 11 seminomas, 14 embryonal carcinoma (ECs), 12 yolk sac tumor (YSTs), 8 teratomas, 10 cases of metastatic melanomas, 14 cases of malignant lymphomas, and 11 cases of metastatic, poorly differentiated carcinoma. SALL4 showed diffuse nuclear labeling for all seminomas, ECs, and YSTs. NANOG showed diffuse nuclear positivity in all seminomas and ECs. Metastatic carcinomas, melanomas, and malignant lymphomas were negative for these 2 markers. Gypican-3, D2-40, and CD30 showed sensitive staining for YSTs, seminomas, and ECs, respectively. In conclusion, SALL4 and NANOG are sensitive and specific markers for GCTs. GPC3, D2-40, and CD30 are sensitive but not specific for individual components of GCTs and may be useful in aiding in the differential diagnosis for the individual component of GCTs when the identity of GCT is established.

Malignant tumors with clear cell morphology: a comparative immunohistochemical study with renal cell carcinoma antibody, Pax8, steroidogenic factor 1, and brachyury

This study aimed to identify an immunohistochemical panel to aid in the differential diagnosis for tumors with clear cell morphology. Twenty-five clear cell renal cell carcinomas (CCRCCs), 19 clear cell ovarian carcinoma (CCOCs), 20 cases of adrenal cortical carcinomas(ACCs), and 10 chordomas were stained for renal cell carcinoma marker (RCC Ma), Pax8, brachyury, and steroidogenic factor 1 (SF-1). The extent of stains was scored as focal (<25%), nonfocal (25%-50%), and diffuse (>50%). The intensity was scored as weak, moderate, and strong. Twenty-two CCRCCs were positive for RCC Ma (88%) and Pax8 (88%), respectively. The RCC Ma cytoplasmic staining was largely diffuse (76%) and strong (76%). The nuclear Pax8 staining was usually diffuse (76%) and moderate (64%) to strong (8%). All of CCRCCs were negative for brachyury and SF-1. All of 19 CCOCs were positive for Pax8 nuclear staining. The staining was diffuse, moderate (21%) to strong (79%). All of CCOCs were negative for RCC Ma, brachyury, and SF-1. All of 20 ACCs were positive for SF-1 nuclear staining. The staining was largely diffuse (95%), moderate (55%) to strong (15%). All of ACC were negative for RCC Ma, Pax8, and brachyury. All of 10 chordomas were positive for brachyury nuclear staining. The staining was diffuse and strong. All of chordomas were negative for RCC Ma, Pax8, and SF-1. In summary, the panel of RCC Ma, Pax8, brachyury, and SF-1 is useful in the differential diagnosis of tumors with clear morphology.