The relationships among tumor-infiltrating lymphocytes, histopathologic findings, and long-term clinical follow-up in renal cell carcinoma.

The relative abundance of tumor-infiltrating mononuclear cells (TIM) was retrospectively evaluated by immunohistology in nephrectomy specimens from 24 cases of human renal cell carcinoma (RCC). The extent of T-lymphocyte (T-cell) and B-lymphocyte (B-cell) infiltration of the tumors was graded semiquantitatively (0 to 4) in each case. Results of this analysis were correlated with clinical evidence of recurrent RCC, histologic evidence of venous invasion, tumor necrosis, and histologic cell type. Clinical follow-up demonstrated the presence of recurrent tumors in four of the 24 cases (17%), and these cases correlated with higher stage and pathologic grade tumors, as well as significantly increased TIM. Venous invasional and tumor necrosis correlated directly with tumor size, pathologic grade, and extent of TIM. Venous invasion was also associated with advanced stage. The group of cases with mixed or granular histologic cell type was associated with advanced stage, high pathologic grade, and increased T-cell infiltration compared to the clear-cell group of tumors. Overall, the pathologic grade demonstrated the highest correlation coefficients with clinical and TNM stage, but also correlated directly with the extent of T-cell infiltration of the tumor. These results confirm previous findings demonstrating a correlation in RCC between increased T-cell infiltration and both high clinical stage and pathologic grade. In addition, increased T-cell infiltration was found to correlate with tumor recurrence, indicating that such infiltration, along with high pathologic grade, is another indicator of poor prognosis in RCC.     

Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features.

The tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder characterized by seizures, mental retardation, and hamartomas. Patients with TSC have been reported to develop renal cell carcinomas (RCC) with increased frequency, an observation that is supported by the Eker rat model. To address the role of the tuberous sclerosis tumor suppressor genes in the pathogenesis of RCC, we studied six TSC-associated RCCs. Our findings suggest that some TSC-associated RCCs have clinical, pathological, or genetic features distinguishing them from sporadic RCC. Clinically, the TSC-associated tumors occurred at a younger age (mean, 36 years) than sporadic tumors and occurred primarily in women. Four of the six patients died of metastatic disease. Pathologically, five tumors displayed clear cell morphology. Of those five, two had high-grade spindle cell areas and one had granular cell histology in addition to the clear cell areas. A sixth tumor was anaplastic throughout. Four of the six tumors immunostained positively for a melanocyte-associated marker, HMB-45. HMB-45 positivity has been seen in two other TSC lesions: renal angiomyolipomas and pulmonary lymphangiomyomatosis. Five tumors were analyzed for loss of heterozygosity. Two had loss of heterozygosity on chromosome 9q34 and one had loss of heterozygosity on chromosome 16p13. We conclude that TSC-associated RCCs occur at an earlier age than sporadic RCCs, that some TSC-associated renal carcinomas have a different immunophenotype than sporadic RCCs, and that the TSC tumor suppressor genes may play a specific pathogenic role in these tumors.     

Integrin distributions in renal cell carcinomas of various grades of malignancy.

We studied 41 renal cell carcinomas, classified according to histologic grades G1 through G3, by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (MAb) against various integrin subunits, and the basement membrane (BM) components laminin and collagen type IV. Selected cases also were immunostained using the avidin-biotin-complex method. The alpha 3 and beta 1 integrin subunits were detected in tumor cells of all the carcinomas. All G1 carcinomas, like normal tubular epithelial cells, expressed the alpha 6 subunit, whereas it was lacking in 20% and 40% of G2 and G3 carcinomas, respectively. Furthermore, when alpha 6 was expressed, a lack of basally polarized organization of the subunit, coupled with disorganization of the BM components, correlated with histologic grade. Another feature that appeared to characterize the more anaplastic tumors was their high level (80%) of the alpha v subunit expression as compared with its absence in the G1 carcinomas. Stromal myofibroblasts, identified by double-labeling with anti-myosin, were often characterized by the expression of the alpha 1, alpha 3, alpha 5 and beta 1 subunits. These results indicate that changes in integrin expression in renal cell carcinomas may be correlated with their degree of histologic malignancy.     

Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior.

Renal medullary carcinoma is a rare, well-recognized highly aggressive tumor of varied histopathology, which occurs in young patients with sickle cell trait or disease. Rhabdoid elements, occasionally seen in high-grade renal tumors including renal medullary carcinoma, possibly represent a pathologic marker of aggressive behavior. INI1 (hSNF5/SMARCB1/BAF47) is a highly conserved factor in the ATP-dependent chromatin-modifying complex. Loss of this factor in mice results in aggressive rhabdoid tumors or lymphomas. In humans, the loss of INI1 expression has been reported in pediatric renal rhabdoid tumors, central nervous system atypical teratoid/rhabdoid tumors and epithelioid sarcomas, a possible primary soft tissue rhabdoid tumor. This study compares five renal medullary carcinomas with 10 high-grade renal cell carcinomas (five with rhabdoid features), two urothelial carcinomas and two pediatric renal rhabdoid tumors. All five renal medullary carcinomas, irrespective of histopathology, showed complete loss of INI1 expression similar to that seen in pediatric renal rhabdoid tumors. In contrast, all renal cell carcinomas or urothelial carcinomas, including those with histological rhabdoid features, expressed INI1. Clinically, all five of the patients with renal medullary carcinoma and the two patients with rhabdoid tumors presented with extra-renal metastases at the time of diagnosis. This study demonstrates that renal medullary carcinoma and renal rhabdoid tumor share a common molecular/genetic alteration, which is closely linked to their aggressive biological behavior. However, the absence of INI1 expression is not necessarily predictive of rhabdoid histopathology but remains associated with aggressive behavior in renal medullary carcinoma.     

Pax-2 expression in adult renal tumors

To assess the expression of the homeogene Pax-2 in adult renal cell carcinomas, we did a retrospective immunohistochemical analysis of 56 frozen tumor samples representing all major histologic subtypes of renal tumors. There were 33 conventional renal cell carcinomas (58.9%), 12 papillary renal cell carcinomas (21.4%), 4 chromophobe cell renal carcinomas, 4 urothelial cell renal carcinomas, and 3 oncocytomas. Forty-five tumors (62.5%) were localized, and 21 tumors had extrarenal involvement. Eight patients (14%) had metastatic disease at the end of the follow-up. We searched for relationships between Pax-2 expression and nuclear grading, TNM staging, Ki-67 proliferation index, expression of transforming growth factor-beta1 (TGF-beta 1), an in vitro down-regulator of Pax-2 expression, and finally cytogenetic abnormalities. All histologic subtypes expressed Pax-2 protein, except urothelial renal carcinomas. The highest expression was in papillary renal cell carcinomas. In this subtype, all tumors and 83.3% +/- 12.3% of tumor cells were immunoreactive for Pax-2. All but 2 conventional renal cell carcinomas expressed Pax-2, but with 26.3% +/- 29.6% of immunoreactive cells (P <.001). Pax-2 expression was not correlated with nuclear grading (P =.6), tumor size (P =.3), and TGF-beta 1 expression (P =.1). Nevertheless, Pax-2 expression correlated with the Ki-67 proliferation index only for the conventional histologic subtype (P =.03). In this histologic subtype, Pax-2 expression was higher in patients with metastatic disease than in those without (P =.02). Pax-2 expression was not associated with specific cytogenetic abnormalities like trisomy 7 (P =.1), 3p deletion (P =.5), and hyperdiploidy (P =.2). TGF-beta 1 expression, positive in 33 tumors (59%), was not correlated with either Pax-2 expression (P =.1) or current prognostic factors such as nuclear grading (P =.2). Interestingly, we also observed an expression of TGF-beta RI and TGF-beta RII in the tumors with high nuclear grading (P =.005). We conclude that Pax-2 protein is expressed in all major histologic subtypes of renal cell carcinomas. The pattern of expression differs between these subtypes. Pax-2 expression in conventional renal cell carcinomas is correlated with the proliferation index and is significantly higher in patients with metastatic disease. HUM PATHOL 32:282-287.     

Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnostics

The term renal cell tumors (adenomas and carcinomas) subsumes the tumors deriving from the uriniferous tubule epithelium of the kidney. Precise analysis shows that the renal cell tumors display different cell types which build up the individual tumor alone or in combination with each other. Three categories of basic elements are distinguished in the characterization of renal cell tumors: Cytological elements = tumor cell types: Clear, chromophobe, chromophilic (basophilic, eosinophilic), oncocytic, spindle-shaped/pleomorphic. Histological elements = growth patterns: Compact, acinar (nest-like), tubulopapillary (tubular, papillary), cystic. Cytological grading of malignancy: G I, G II, G III; mainly based on the degrees of nuclear atypia. The cytological features are given priority compared to the histological growth forms for classification of renal cell tumors. However, the latter are not to be neglected in the overall evaluation of a tumor. A classification of renal cell tumors is suggested and the result of its application in 510 renal cell carcinomas and oncocytomas is presented. On this basis and in connection with the cytological grading, a more precise prognostic evaluation of the renal cell carcinomas is expected.     

T2-weighted fast spin-echo MR findings of adenocarcinoma of the uterine cervix: comparison with squamous cell carcinoma.

The purpose of this study was to investigate the differences in MR findings of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix and to compare MR findings with pathologic findings. MR images of 17 patients with pathologically proven AC, using a fast spin-echo (FSE) T2-weighted image (T2WI) with pelvic phased-array coil on a 1.5-T unit, were retrospectively evaluated. After measurement of the signal intensity (SI) ratios of the region of interest between tumors and gluteus maximus muscle, we compared the ratios of AC with those of 16 patients with SCC. AC showed relatively high SI on FSE T2WI with multiseptated lesions in four cases and hydrometrocolpos in three cases. The mean SI ratio was 3.82 +/- 1.68 in AC and 2.35 +/- 0.42 in SCC (p < 0.0001, t-test). Multiple tumorous glands with cytoplasmic and intraglandular mucin or serous fluid were pathologically found in AC, but SCC revealed the compact cellularity of stratified squamous tumor cells. The cervical AC showed higher SI than SCC on FSE T2WI with occasional multiseptated lesions and hydrometrocolpos. If the SI ratio of the tumor was more than 3.0, AC could be diagnosed with a sensitivity of 68.8% and a specificity of 100%.     

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.     

Different immunohistochemical patterns of Fhit protein expression in renal neoplasms.

BACKGROUND: The FHIT gene on human chromosome 3p14.2 is deleted in a variety of malignant tumors, including clear cell renal carcinomas (RCCs) resulting in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investigated the association of Fhit expression with particular subtypes of renal tumors to determine the role and specificity of this putative tumor suppressor gene in renal neoplasia. MATERIAL AND METHODS: The immunohistochemical expression of Fhit was tested in normal kidneys and in 109 renal neoplasms consisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinomas, six oncocytomas, four pelvic transitional cell carcinomas and 20 Wilms' tumors from formalin fixed and routinely processed tissue. RESULTS: Normal renal tubules expressed Fhit strongly and consistently. The majority (78%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas the majority (74%) of papillary carcinomas, all chromophobe renal cell carcinomas, and oncocytomas were strongly positive. Sixty-eight percent of low-grade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinomas were Fhit negative. Wilms' tumors demonstrated focal staining in the epithelial component in 8 of 20 cases (40%). CONCLUSIONS: The loss of Fhit expression in a high percentage of clear cell RCCs with conservation of Fhit in other types of tumors supports the proposed role of FHIT alterations in the genesis of clear cell carcinomas in contrast to other types of renal epithelial tumors. FHIT expression may play a role in epithelial differentiation of nephroblastomas (Wilms' tumors).     

Analysis of nm23 expression as a prognostic parameter in renal cell carcinoma.

To identify the clinicopathological events including nm23 expression that underlies progression in renal cell carcinoma, a retrospective analysis of patients with renal cell carcinoma was performed. Ninety-eight cases of radical nephrectomies with extensive regional or para-aortic lymph node dissection were assessed for clinicopathological variables, and eighty-five cases underwent nm23/NDPK-A protein immunohistochemical staining. Significant parameters in survival were tumor size, histologic pattern, Fuhrman''s nuclear grade, pathologic T(pT) stage, pathologic N stage, M stage, tumor thrombi, location of metastasis, and nm23 staining intensity. To assess the relationship with survival, the tumors with low and high nm23 expressions were compared. The fifty-nine patients with a high staining intensity had a significantly worse survival than did the twenty-six with a low staining intensity (p = 0.0015). Additionally nm23 staining intensity was correlated with tumor size, Fuhrman''s nuclear grade, pT, and distant metastasis. Therefore, the immunostaining intensity of nm23 protein could be used as a prognostic parameter with an inverse correlation.     

Immunogold analysis of antioxidant enzymes in human renal cell carcinoma

Analysis of activities of the antioxidant enzyme manganese superoxide dismutase in human renal cell carcinomas often showed greatly altered enzyme levels (either elevated or depressed) compared to the cell of origin, the kidney proximal tubule. In order to better understand the variability observed, immunogold studies were performed on human renal cell carcinomas using a polyclonal antibody to human kidney manganese superoxide dismutase. For comparison, studies were also performed using antibodies to other antioxidant enzymes. For histologic studies, renal cell carcinomas were subclassified on the basis of light microscopy and ultrastructural analysis into clear cell, granular cell, or mixed clear and granular cell variants. In all three types of tumor, immunogold studies showed little staining using antibodies to copper, zinc superoxide dismutase or glutathione-dependent enzymes. However, intensity of labeling for manganese superoxide dismutase and catalase depended on the cell type(s) in the tumor. Clear cell variants demonstrated trace staining for manganese superoxide dismutase and catalase, while granular cell variants exhibited heavy staining for both of these enzymes. Mixed types of tumors showed clear cells with trace staining for all antioxidant enzymes examined, while granular cells again showed intense labeling for manganese superoxide dismutase and catalse. Using normal kidney proximal tubule as a comparison, immunogold ultrastructural analysis using antibody to manganese superoxide dismutase demonstrated infrequent small lightly labeled mitochondria in clear cell variants, while granular cell variants exhibited numerous medium-sized heavily labeled mitochondria. These data suggest that: 1) the variability in activity values for manganese superoxide dismutase may be due to heterogeneity of cell types in these tumors and 2) manganese superoxide dismutase immunoreactive protein was elevated in granular cells both because of an increase in number of mitochondria and because the labeling density in mitochondria was increased compared to mitochondria in clear cell types or in normal proximal tubular cells.     

Chromosomes in kidney, ureter, and bladder cancer

Although Wilms tumor has been a favored subject for cytogenetic investigation, little is known about chromosomes in adult urinary tract cancers. For this reason, we excluded Wilms' tumor and studied a series of 32 adult urinary tract tumors. Nineteen tumors had detectable autosomal abnormalities. Each of ten renal tumors (consisting of eight renal cell and two transitional cell carcinomas) had three or more chromosome abnormalities. Two candidates for primary chromosome changes in renal cancer are rearrangement of 3p14 and an unbalanced translocation with breakpoints of 5q13 and 14q22. Trisomy 20 is a frequent secondary change. Other nonrandom changes in renal cancer are rearrangements of 1q and +7, -8, -9, -14, -15, +16, and deletions of 17p. Eight bladder and a ureter tumor were all transitional cell carcinomas. Two bladder and the ureter tumor had only one detectable abnormality: deletions of 10q24 and 21q22 and +7, respectively. Other nonrandom bladder changes were -9, +13, +15, and +20. From a cytogenetic standpoint, adult urinary tract tumors appear to be chromosomally complex but critical consistencies are emerging.     

Multilocular cystic renal cell carcinoma

Multilocular cystic renal cell carcinoma (MCRCC) appears to be a distinct subtype of renal cell carcinoma with characteristic gross and microscopic features. The authors' ten-year experience (1977-1987) included six cases of MCRCC that were followed for a minimum of two years, with neither recurrence nor metastasis observed in any of the cases. During this period, there were 855 urologic procedures for the upper urinary tract, with 256 neoplasms or cysts identified. These included 32 simple cysts, 41 transitional cell carcinomas, 133 renal cell carcinomas, 17 papillary renal cell carcinomas, and 33 miscellaneous tumors. Histologically, the MCRCCs were well-demarcated multicystic lesions containing variably sized aggregates of neoplastic clear cells showing grade 1 nuclear features and little or no mitotic activity. The cyst walls were densely fibrotic, and the lining was often devoid of epithelium. Flow-cytometric analysis performed in five of the six cases with the use of paraffin-embedded tissue showed the tumors to be diploid in all instances, with low proliferative activity. The authors believe that this tumor is a low-grade variant of renal cell carcinoma and should be studied further to determine appropriate therapy.     

Hepatocarcinomas, cholangiocarcinomas, and hepatoblastomas produced by chemically transformed cultured rat liver epithelial cells. A light- and electron-microscopic analysis.

The histology and ultrastructure of more than 100 tumors produced by a chemically transformed rat liver epithelial cell line and its single-cell-derived clonal subpopulations were studied. Wide-ranging morphologic presentations were observed, including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors. In addition to epidermoid and adenocarcinomas, several tumors were morphologically indistinguishable from hepatocellular carcinomas. The "mixed epithelial-mesenchymal" tumors reproduced most of the various histologic features of human hepatoblastomas. In many instances, the epithelial component occupied focal areas of tumors, and transmission electron microscopic studies of the "sarcomatous" regions revealed either spindle-shaped epithelial tumor cells or, in most cases, scattered epithelial tumor cells surrounded by numerous fibroblasts or myofibroblasts. Similar findings were observed in several "sarcomas" examined ultrastructurally, which suggests that most of the mixed tumors or sarcomas actually were spindle cell carcinomas and/or carcinomas with marked host fibroblastic reaction. However, in a few mixed tumors produced by clonally derived cell strains, unequivocal carcinosarcomas with neoplastic osteoid or chondroid tissue were demonstrated. The findings of this study are discussed in the context of current insights on the cellular composition of the liver and on the histogenesis of human hepatoblastoma.     

Fas (APO-1/CD95) ligand and Fas expression in renal cell carcinomas: correlation with the prognostic factors

BACKGROUND AND OBJECTIVE: Fas ligand (FasL, CD95L) is a type II transmembrane protein of the tumor necrosis factor family that induces cells to send an apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, conferring a survival advantage. It is important to understand FasL and Fas expression in tumors, because the growth of cancer might be controlled by Fas-mediated apoptosis. METHODS: The expressions of FasL and Fas were studied by immunohistochemical analyses in 51 cases of renal cell carcinomas and the adjacent normal renal tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and histologic types. RESULTS: In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cases, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunostaining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and low expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clinical stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P<.001). CONCLUSION: These data indicate that high expression of FasL and low expression of Fas protein in renal cell carcinomas may play a role in evading surveillance of the immune system. In addition, the FasL and Fas expressions appear to have a therapeutic implication for high-grade tumors rather than a prognostic one.     

Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma

Hepatocellular carcinoma may share histologic features with a wide variety of epithelial tumors. To facilitate its pathologic diagnosis, clinical and pathologic material was reviewed from 62 patients with hepatocellular carcinoma and immunostaining was performed with polyclonal anti-carcinoembryonic antigen (pCEA), monoclonal anti-carcinoembryonic antigen (mCEA), anti-epithelial membrane antigen (EMA), and an antikeratin (KER AE1/AE3). Clinical information and follow-up were available for all patients from several sources. Cases with ambiguous clinical data or findings suggestive of metastatic carcinoma to the liver were excluded. In addition, the following tumors were immunostained and compared to hepatocellular carcinoma: 10 cholangiocarcinomas; 14 pancreatic adenocarcinomas; 4 gastric adenocarcinomas; 3 breast carcinomas; 5 renal carcinomas; 3 combined germ cell tumors of the testis; 3 adrenal cortical carcinomas; and 4 melanomas. The pCEA stained bile canaliculi in normal liver and in 39 of 62 (63%) hepatocellular carcinomas. This canalicular staining pattern of pCEA was unique to hepatocellular carcinoma. The mCEA (1 of 62, 1.6%) was almost always negative, and KER AE1/AE3 (9 of 59, 15.3%) was occasionally positive. The EMA stained 25 of 62 (40.3%). The adrenal cortical carcinomas and melanomas were negative for all antigens except rare pCEA and focal EMA staining in an adrenal tumor. Other carcinomas showed cytoplasmic pCEA (36 of 44, 81.8%), mCEA (40 of 46, 87.7%), EMA (41 of 43, 95.4%), and KER AE1/AE3 (42 of 44, 95.5%). Canalicular staining with pCEA is specific for hepatocellular carcinoma, while negativity with mCEA and KER AE1/AE3 is suggestive of hepatocellular differentiation.     

Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosal carcinomas

Although numerous studies have assessed the biologic parameters of tumors, measurement of these parameters has had, to date, little impact on histologic diagnosis. Furthermore, analysis of a single parameter is insufficient to evaluate tumor malignant potential. In the present study, cell proliferation, DNA ploidy and p53 product were analyzed to objectify the tumor malignant potential in colorectal adenomas and intramucosal carcinomas. Sixty-one adenomas and 49 intramucosal carcinomas were studied using immunohistochemical analysis of Ki-67 and p53, silver-staining nucleolar organizer region (AgNOR) stain and DNA ploidy in fresh samples. Intramucosal carcinoma exhibited a greater Ki-67-positive rate and AgNOR count than the adenomas, although these parameters varied widely among samples. The incidence of aneuploidy and p53 over-expression in colorectal intramucosal carcinomas was significantly higher than in colorectal adenomas. These results indicate that DNA aneuploidy and p53 accumulation are the most reliable parameters for distinguishing benign and malignant lesions.     

MRI of the breast: comparison of MRI signals and histological characteristics of the same slices

The development of MRI with high spatial resolution and a special breast coil has contributed to more-accurate diagnosis of breast tumor, such as determination of morphologic characteristics including internal architecture of the breast lesion. To clarify how individual MRI findings reflect the pathological findings, we made slices of resected breast lesions identical to those obtained with axial MRI and compared them respectively according to histological subtype of tumors. In this article, we present MRI findings on the basis of histopathological evidence. In general, fibroadenomas (FA) show a well-defined border on contrast-enhanced fat-suppressed T₁-weighted images (CFT1). However, a subtype of fibroadenoma, mastopathic type, with a poorly defined border on CFT1 and carcinoma-like enhancement, is similar to cancer on MRI. Scirrhous carcinomas take either of two patterns on dynamic MRI, i.e., homogeneous enhancement or thick irregular peripheral ring enhancement. The latter type shows central fibrosis zones histologically. Papillotubular carcinoma shows a spotted pattern on dynamic MRI. The low-enhancement areas within the spotted pattern reflect parenchyma between clusters of cancer. Solid-tubular carcinoma shows thin peripheral enhancement on dynamic MRI and linear high signal on CFT1. This finding of CFT1 corresponds to infiltration of lymph cells and fibroblast cells in the adjacent zone. Invasive lobular carcinoma shows nonmass lesions and a slow gradual enhancement pattern. Mucinous carcinomas show high signal intensity on T₂-weighted images because of mucin and reveal gradual enhancement. The ill-defined border of mucinous carcinoma on CFT1 is useful to distinguish it from FA.     

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.