[Show abstract][Hide abstract] ABSTRACT: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA-IX, Ksp-cadherin, CD82 and CK7.
Pathology International 02/2015; 65(3). DOI:10.1111/pin.12254 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With the aim of standardizing Ki-67 immunohistochemistry, we assessed interobserver and interlaboratory variability of the Ki-67 labeling index and Ki-67 score among eight general pathologists for 24 gastrointestinal stromal tumors (GISTs) and 12 leiomyosarcomas, which were predominantly of the gastrointestinal (GI) tract, mesentery and retroperitoneum, based on a review of a tissue microarrays subjected to immunohistochemistry with antibodies for Ki-67. For Ki-67 immunostaining of mesenchymal tumors of the GI tract, including GISTs, differences were seen in the scores given by regional hospitals. Conversely, for two categories of the Ki-67 labeling index, namely <10% and ≥10%, concordance of the Ki-67 score between microscopic observation and image analysis, and between the observers, was good, but it was not good for the other four categories of the index for <5%, 5-9%, 10-29%, and ≥30%. The concordance of the Ki-67 scores between the observers in two categories was higher using the Ki-67 pre-stained tissue microarrays (TMAs) within each participating institute than that using the Ki-67 stained TMAs between the participating institutes. The reproducibility of a 10% cut-off value for the Ki-67 labeling index to predict the prognosis of GISTs was relatively high, but there is an urgent need to standardize the staining technique.
Pathology International 02/2013; 63(2):102-7. DOI:10.1111/pin.12038 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder characterized by fibrofolliculomas, renal tumors, and pulmonary cysts with recurrent pneumothorax. Multiple pulmonary cysts and pneumothorax are the key signs for diagnosing BHD syndrome. The pathologic features of BHD pulmonary cysts, however, are poorly understood. This disorder is caused by mutations in the gene that encodes folliculin (FLCN). FLCN is regarded as a tumor suppressor; it mediates cellular activities by interacting with the mammalian target of rapamycin (mTOR). In this study, we investigated the lungs of 11 patients from 9 BHD families. The majority of patients consulting doctors were women between 30 and 60 years of age who had pulmonary cysts and repeated pneumothoraces. Genomic DNA testing revealed 5 different mutation patterns. Histopathologic examination found that the inner surface of cysts was lined by epithelial cells, sometimes with a predominance of type II pneumocyte-like cuboidal cells. The cysts occasionally contained internal septa consisting of alveolar walls or showed an "alveoli within an alveolus" pattern. The cells constituting the cysts stained positive for phospho-S6 ribosomal protein expression, suggesting activation of the mTOR pathway. Although BHD pulmonary cysts are frequently misdiagnosed as nonspecific cystic diseases, they are distinctly different in histopathology from other bullous changes. Mechanical stress such as rupture and postrupture remodeling allows mesothelial invagination and fibrosis. Such modified BHD pulmonary cysts are virtually indistinguishable from nonspecific blebs and bullae. We propose a new insight, namely, that the BHD syndrome-associated pulmonary cyst may be considered a hamartoma-like cystic alveolar formation associated with deranged mTOR signaling.
The American journal of surgical pathology 04/2012; 36(4):589-600. DOI:10.1097/PAS.0b013e3182475240 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.
[Show abstract][Hide abstract] ABSTRACT: The authors performed extensive transperineal ultrasound-guided template prostate biopsies to investigate carcinoma core distribution.
Between August 2000 and May 2004, 371 men underwent template biopsies. Three hundred twelve patients had not undergone a previous biopsy (first group) and 59 had undergone previous transrectal sextant biopsies (repeat group). Of the 312 patients in the first group, 236 had normal digital rectal examination (DRE) findings (DRE- first group) and 76 patients had an abnormal DRE (DRE+ first group). A mean of 20.1 biopsy cores (range, 9-38 cores) was taken from the entire prostate. The region > 2.0 cm from the rectal face of the prostate was defined as the anterior region and the remaining area was defined as the posterior region.
In the DRE- first group, the carcinoma core rate (number of tumor cores/number of biopsy cores) in the anterior region (7.2%) did not differ from that of the posterior region (7.3%) (P = 0.9635). However, in the DRE+ first group, the carcinoma core rate in the posterior region (22.0%) was found to be higher than in the anterior region (13.2%) (P < 0.0001). In the repeat group, the carcinoma core rate in the posterior region (3.1%) was significantly (P = 0.0008) lower than that exhibited in the anterior region (7.2%).
The results of the current study suggest that nonpalpable prostate carcinoma is distributed equally within the entire prostate, although palpable carcinoma is distributed mainly in the posterior region and many of the tumor foci in the anterior region may be missed by a transrectal sextant biopsy. The examination of radical prostatectomy specimens is required to prove these results.
Cancer 05/2005; 103(9):1826-32. DOI:10.1002/cncr.21020 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We performed extensive transperineal ultrasound guided template prostate biopsy and evaluated cancer core distribution.
From August 2000 to May 2002, 113 men with prostate specific antigen levels between 4.0 and 10.0 ng/ml underwent template biopsy. Eighty-six had no previous biopsy (first group) and 27 had previous transrectal sextant biopsies (repeat group). A mean of 18.4 biopsy cores were taken. We defined the region over 2 cm from the rectal face of the prostate as the anterior region and the other as the posterior.
Cancer was detected in 49 of 113 (43%) men. Forty-two were in the first group and seven in the repeat group. In the first group, the cancer core rate (cancer core number/biopsy core number) in the anterior region (7.0%) had no difference from that in the posterior region (8.6%) (P = 0.7111). But in the repeat group, the cancer core rate in the anterior region (4.6%) was higher than in the posterior (1.5%) (P < 0.0001).
These results suggest that transrectal sextant biopsies miss more cancers in the anterior region than in the posterior. We believe template technique has an advantage to be able to detect cancer equally in the anterior and posterior.
The Prostate 01/2004; 58(1):76-81. DOI:10.1002/pros.10298 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A severe case of placental mesenchymal dysplasia occurred in association with intrauterine fetal death (IUFD). The gravida-1, para-1 mother was a 26-year-old Japanese. The first pregnancy was unremarkable and a healthy female infant was delivered. The present pregnancy had been uneventful until 34 weeks of gestation when IUFD was detected. The 1516-g (mean +/- SD, 2050 +/- 387 g) stillborn infant had no external abnormalities and the karyotype was 46,XX. The placenta was markedly enlarged (1050 g; mean +/- SD, 452 +/- 202 g), and approximately 80% was occupied by extraordinary enlarged villous structures with a myxoid appearance. Histologically, the dysplastic villi had myxoid stroma and a decreased number of, occasionally obliterated, fetal vessels. There was no abnormal trophoblastic proliferation. Large-sized fetal vessels in the chorionic plate frequently contained organized thrombi. This is the first case of placental mesenchymal dysplasia, which possibly lead to the IUFD.
Pathology International 10/2000; 50(9):759-64. DOI:10.1046/j.1440-1827.2000.01100.x · 1.69 Impact Factor