Tubulocystic Pattern Research Articles

Tubulocystic Carcinoma of Bile Ducts: A Distinct Type of Cholangiocarcinoma Associated With Adenofibroma-type Lesions.

A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of these were also investigated with next-generation sequencing with a 174 genes panel. The patients were 5 males and 3 females, with a mean age of 64.6. All tumors were intrahepatic except for one perihilar that protruded into soft tissues. The mean size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern that closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules, and occurring in the background of adenofibromatous lesions. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures, one had areas transitioning to intraductal tubulopapillary neoplasm, and 3 cases harbored more conventional small-duct CCA foci. In those 3 cases, both the tubulocystic and conventional CCA components were investigated by next-generation sequencing separately, and they shared the molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A , BAP1 , and PBRM1 , and the actionable FGFR2-MCU fusion gene. In the limited follow-up, all but one were alive and free of disease after surgical resection. In conclusion, we described a distinct entity of CCA with specific histo-molecular features, for which we propose the designation of tubulocystic carcinoma of bile ducts.

Spatial profiling of ovarian clear cell carcinoma (OCCC) and identification of immune-hot features.

e17543 Background: OCCC is an ovarian cancer subtype with high incidence in Asia. Despite its frequent occurrence as an early-stage disease, optimal therapeutic options for high-risk patients are limited. Recently, immune-hot features have been proposed as an indicator for poor prognosis for early-stage OCCC. Specific patterns of intra-tumoral heterogeneity (ITH) associated with these immune-hot features have yet to be defined. Methods: Formalin-fixed paraffine embedded (FFPE) tumor sections from 10 early-stage primary OCCC patients were included. Digital Spatial Profiling (DSP) of 18 protein targets from the Human Protein Core Panel was conducted by using the nanoString GeoMx system to profile selected regions of interest (ROIs) based on the reference H&E staining morphology. Areas of illumination (AOIs) were defined according to ROI segmentation by the fluorescence signals of pan-cytokeratin (PanCK), CD45, or DNA. The digital signals were quantified by the nanoString nCounter system. Results: Unsupervised hierarchical clustering of 252 AOIs from 229 ROIs showed 5 distinct clusters. PanCK+ AOIs distributed in 5 clusters were found to express combinations of markers suggestive of immune mimicry: granzyme B (GZMB) high epithelial cells (C1-a), immune signal high epithelial cells (C1-b), immune-like cells (C1-c), fibronectin-high epithelial cells (C2-a), and signal-cold epithelial cells (C2-b). CD45+ AOIs were mostly clustered in C1-c. Tumor cells with C1-c and C2-a features were associated with recurrence while those in C1-a were associated with no recurrence (Chi-square p=2.8E-04). Tumor infiltrating immune cells (TIIs), which were found to be more enriched of the macrophage lineage (stronger CD68 expression, p=4.5E-03), were associated with recurrence (66.7% in recurrence vs 14.3% in no recurrence, Chi-Square p=0.098). TIIs appeared in PanCK segments of C1-b and C1-c with higher frequencies (45% in C1-b, 25% in C1-c, Chi-square p=0.046) and in PanCK segments of C1-a with extremely low frequency (0%). Correlating with morphology, tumors with recurrence showed higher frequency of papillary pattern (54.7%, Chi-Square p=1.01E-04) and lower frequency of tubulocystic pattern (18.9%, Chi-Square p=7.21E-03). Plus, TIIs were found with high frequency in ROIs with papillary pattern (65.2%, Chi-Square p=4.99E-04) and low frequency in ROIs with tubulocystic pattern (8.7%, Chi-Square p=6.43E-03). Papillary ROIs, which showed macrophage lineage immune mimicry, high CD68 intensity and low PanCK intensity, were found to have very low frequency of PanCK segments of C1-a (6.2%, Chi-Square p=1.26E-04), but extremely high frequency (100%) of PanCK segments of C1-c. Conclusions: Spatial profiling of early-stage OCCC tumors revealed immune-hot tumor features associated with recurrence. These features included immune mimicry of tumor cells, the presence of TIIs, and a papillary pattern in morphology.

Clear Cell Carcinoma of Ovary - Rare Subtype with Poor Prognosis: A Case Report

Ovarian clear cell carcinoma is a rare subtype of epithelial carcinoma of ovary having poor prognosis. This tumor has been found to be associated with endometriosis and has similarities with the pathogenesis of endometrioid carcinoma. We report a case of 37 years female presenting with the pain in right lower abdomen. Computerized Tomography revealed right ovarian cystic mass. Histopathology showed tubulocystic pattern of arrangement of tumor cells with few foci showing hobnail cells which confirmed the diagnosis. Keywords: Clear cell carcinoma, Ovary, Poor prognosis

Clear cell carcinoma of the urinary bladder: a systematic review.

We conducted a systematic review of the literature on primary clear cell carcinoma (CCC) of the urinary bladder. A literature search using keywords and MeSH terms related to "clear cell carcinoma", "clear cell adenocarcinoma", "mesonephroma" and "urinary bladder" in EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials was performed. A manual search was performed with web-based search engine Google Scholar. Reference lists of the included studies were screened for additional articles. Articles up till 16th July 2020 were retrieved. Observational human studies on primary CCC in urinary bladder with English full-text were included for further analysis. 904 articles were identified and 44 articles were included for further analysis. Data including clinical features, tumour characteristics, treatment and oncological outcomes were reviewed. There were 70 patients (44 females and 26 males) reported in literatures and included in this review. Gross haematuria was the most common presentation (79.7%), followed by irritative urinary symptoms (47.5%). Regarding the histology, tubulocystic pattern is the most common histologic pattern (49.1%), and 52.6% had muscle invasion. Most cases were CK7 (96.6%) and CK20 (88.9%) positive. CA125 (96%) was commonly positive, indicating its potential origin from mullerian duct. Most patients received surgery (95.5%) as primary treatment. However, the oncological outcomes were unsatisfactory with a 2-year survival rate of 60.0%. Clear cell carcinoma is an uncommon subtype of bladder cancer which can be diagnosed by histology and immunohistochemical staining result. The majority of patients presented with muscle invasion and had a poor survival despite aggressive treatment.

Fumarate hydratase-deficient renal cell carcinoma: A clinicopathological study of seven cases including hereditary and sporadic forms

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) has been incorporated into the recent international histological classification of renal tumors. However, to date, there are limited studies describing the clinicopathological features of fumarate hydratase (FH)-deficient RCC, including the hereditary (HLRCC) and sporadic forms. Herein, we present a clinicopathological study of seven cases with FH-deficient RCC. The age of patients ranged from 26 to 70 years with mean and median age of 51.7 and 57 years, respectively. The follow-up data of all patients were available. One patient was alive without the disease and five patients were alive with active disease. One patient died of the disease. Family history of RCC, or skin or uterine smooth muscle tumor within second degree of kinship was present in four of seven patients. Metastasis was observed in all tumors. Metastatic sites included bone, lungs, liver, peritoneum, ovaries, tonsils, or lymph nodes. Grossly, the cut surface of the tumor usually showed light brown, brown, or whitish color. Microscopically, the cytoplasm of the tumor cells was predominantly eosinophilic and all tumors displayed various architectural patterns such as papillary, tubular, solid, or microcystic patterns. Furthermore, two tumors demonstrated a tubulocystic pattern. Sarcomatoid change and rhabdoid features were seen in five tumors and two tumors, respectively. Large cytomegaloviral (CMV) inclusion-like eosinophilic nucleoli surrounded by a clear halo were identified in all tumors. All tumors showed negative immunohistochemical reaction for FH protein. False positive results of TFE3 protein were observed in three tumors. Furthermore, a germline mutation of FH gene was identified in one patient with family history of the disease. In conclusion, FH-deficient RCC includes hereditary and sporadic forms. Grossly, this tumor is solitary and occurs unilaterally. Histologically, the tumor is characterized by various patterns such as papillary, tubular, solid, tubulocystic, or microcystic, has eosinophilic cytoplasm and CMV-like high-grade nuclei. FH-deficient RCCs frequently metastasize to other anatomic sites. TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene.

Clinicopathological and molecular features of hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas

AimsHereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by germline mutations in fumarate hydratase (FH). Affected families have an increased risk of renal cell carcinoma...

Pigmented microcystic chromophobe renal cell carcinoma: a clinicopathologic analysis of five cases

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People's Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions: Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.

Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seventeen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1β did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap with primary neoplasia. However, the expected morphology and immunophenotype of CCRCC are maintained in most gynecologic tract metastases. As such, although metastatic CCRCC and müllerian CCC may display significant overlap in pathologic features, several morphologic and immunophenotypic features are useful in their distinction.

Oncocytoma, Tubulocystic Pattern with Papillary Features: A Diagnostic Challenge

Oncocytoma, Tubulocystic Pattern with Papillary Features: A Diagnostic Challenge

Molecular Genetic Alterations in Renal Cell Carcinomas With Tubulocystic Pattern: Tubulocystic Renal Cell Carcinoma, Tubulocystic Renal Cell Carcinoma With Heterogenous Component and Familial Leiomyomatosis-associated Renal Cell Carcinoma. Clinicopathologic and Molecular Genetic Analysis of 15 Cases.

The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested.

Clear cell adenocarcinoma of the male urethral tract

We present a rare case of clear cell adenocarcinoma of the male bulbomembranous urethra. Mostly these tumors have been described in the female urethral tract with its possible origin from mullerian remnants, wolffian remnants or paraurethral glands. Histologically, these tumors have typically tubulocystic pattern comprising of hobnailed cells with clear glycogenated cytoplasm along with well-defined cytoplasmic membranes. This case is being presented due to its rarity, aggressive behavior and to discuss, trauma as its possible etiological factor.

Clear cell adenocarcinoma of the urinary bladder: a short review.

In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a mullerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma.

Clear Cell Adenocarcinoma of the Urinary Bladder: A Short Review

In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a müllerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma.

Review of chromophobe renal cell carcinoma with focus on clinical and pathobiological aspects.

In recent years, the concept of chromophobe renal cell carcinoma (RCC) has been established. Chromophobe RCCs account for about 4-6% of all renal tumors. Macroscopically, the cut surface of the tumor is generally grey-beige in color. Histologically, there are two variants (typical and eosinophilic). In the typical variant, large tumor cells with architecture of a compact tubulo-cystic pattern proliferate. The cytoplasm is abundant and shows a fine reticular translucent pattern. The cell border is thick, prominent and eosinophilic. In the eosinophilic variant, tumor cells are smaller and markedly eosinophilic, and a perinuclear halo is often seen. Histochemically, the tumor cells generally show a diffuse and strong reaction for Hale's colloidal iron staining. Ultrastructurally, tumor cells contain many cytoplasmic microvesicles (150-300 nm). In chromosomal analysis, a low chromosome number is characteristic of chromophobe RCCs, due to the frequent occurrence of a combined loss of chromosomes 1, 2, 6, 10, 13, 17, and 21. In differential diagnosis, histological distinction from oncocytomas, which share a common phenotype (intercalated cells of the collecting duct system), is most important. In this diagnostic setting, recent studies have given rise to several problems. Firstly, some cases of coexistent chromophobe RCC and oncocytoma (so-called renal oncocytosis) or cases of oncocytoma with metastasis have recently been reported. Secondly, the existence of chromophobe adenoma, which is the benign counterpart of chromophobe RCC, and an oncocytic variant of chromophobe RCC has recently been suggested. Therefore, further studies are needed to elucidate the relationship between chromophobe RCCs and oncocytomas, to confirm whether chromophobe adenoma actually exists or not, and to identify the key gene that causes chromophobe RCCs.

Low-grade Collecting Duct Carcinoma Of The Kidney: A Potential Mimic Of Conventional Clear Cell Carcinoma

Collecting duct carcinoma of the kidney is a well-known, but relatively uncommon tumor characterized by a high cytologic grade, desmoplastic stroma and a poor clinical outcome. Since 1979, however, there have been several reports of low-grade renal carcinoma of putative collecting duct origin. These low-grade tumors were extensively papillary, tubulopapillary or tubulocystic, with a low nuclear grade (usually Furhman grade 1 or 2). Most have conferred a benign follow-up course, even when treated only by partial nephrectomy. The previous reports of such tumors have been variably characterized immunohistochemically and ultrastructurally. We report the cases of a low-grade renal carcinoma of collecting duct origin, arising in the right renal lower pole of a 47-year-old-male with a history of gout and nephrolithiasis. Microscopically, the tumor showed a tubular and tubulocystic pattern and was composed almost exclusively of clear cells, closely mimicking conventional (clear cell) renal cell carcinoma. Tumor cells stained positively for PAS, showed droplet-like staining with Hale\'s colloidal iron, were variably alcian blue positive and were mucicarmine negative. They were reactive with immunohistochemical antibodies to peanut agglutinin (PNA), Ulex europaeus-1 agglutinin (UEA-1), pan-cytokeratin, CAM 5.2, cytokeratin 7, epithelial membrane antigen (EMA) and vimentin. Electron microscopy showed microvillous-lined tubules, desmosomes, and tonofilaments, with a paucity of mitochondria. The patient was treated by partial nephrectomy and has been without evidence of disease for a follow-up period of 10 months.

Renal Oncocytoma: A Reappraisal of Morphologic Features With Clinicopathologic Findings in 80 Cases

Renal oncocytoma has several features that overlap with other renal neoplasms with a preponderance of granular cytoplasm, such as chromophobe, granular, and papillary renal cell carcinomas. Lack of knowledge of this entire spectrum of eosinophilic renal cell neoplasms has led to several misconceptions in the literature regarding renal oncocytoma. These include the of oncocytomas, metastatic oncocytomas, and the impression that renal oncocytoma is usually low grade and lacks prominent nucleoli. In order to further characterize the histologic features and embelLish diagnostic criteria, we evaluated 93 tumors from 80 patients. Four tumors were bilateral and two were multifocal. The mean age was 67.2 years (32-89 years), men were more commonly affected (3.1:1), and 82.7% tumors were incidental findings. Grossly, the tumors were mahogany brown, lacked necrosis, and averaged 4.4 cm in size (range 0.6-15 cm). Histologically, renal oncocytoma was composed of an exclusive or predominant component of acidophilic cells with three architectural patterns of disposition: (a) The classic (57.5%), composed of a characteristic nested or organoid arrangement of cells, each surrounded by a distinct reticulin framework; (b) a pattern (6.3%) with numerous closely packed cystically dilated tubular structures; and (c) mixed pattern (36.2%), which had both the organoid and tubulocystic patterns. A gross or microscopic scar was noted in 53.8% cases, and histologically a distinctive myxoid and/or hyalinized stroma separated nests of cells. Generally, the nuclei of renal oncocytoma were round with uniform nuclear contours. Nearly half of the tumors had prominent nucleoli (42.5% had prominent nucleoli equivalent to Fuhrman's grade III or IV). Pleomorphism was absent in 50% of cases but was conspicuous in 12.5% of cases including foci of bizarre cells. Other atypical features included perinephric fat involvement (11.3%), renal parenchymal invasion not associated with desmoplasia (10%), and hemorrhage (31.3%). Renal oncocytoma by definition lacks areas of clear cell carcinoma, significant lesional necrosis, or conspicuous papillary formations. Ancillary features noted included normal-appearing renal tubules within the lesion (15%), intranuclear holes (20%), psammoma bodies (7.5%), and foam cells (7.5%). 15% of tumors were locally excised, and 85% resulted in radical nephrectomy. Mean follow-up of 7.6 years (range 15-200 months) showed no evidence of recurrence, metastasis, or death due to tumor. In conclusion, renal oncocytoma, herein described, is a benign neoplasm and therefore does not merit a nuclear grading scheme. It has unique histologic features including an organoid and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some atypical findings including nuclear pleomorphism, prominent nucleoli, and adjacent renal parenchymal and perinephric fat involvement.

Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases.

Renal oncocytoma has several features that overlap with other renal neoplasms with a preponderance of granular cytoplasm, such as chromophobe, granular, and papillary renal cell carcinomas. Lack of knowledge of this entire spectrum of eosinophilic renal cell neoplasms has led to several misconceptions in the literature regarding renal oncocytoma. These include the "grading of oncocytomas," "metastatic oncocytomas," and the impression that renal oncocytoma is usually low grade and lacks prominent nucleoli. In order to further characterize the histologic features and embelLish diagnostic criteria, we evaluated 93 tumors from 80 patients. Four tumors were bilateral and two were multifocal. The mean age was 67.2 years (32-89 years), men were more commonly affected (3.1:1), and 82.7% tumors were incidental findings. Grossly, the tumors were mahogany brown, lacked necrosis, and averaged 4.4 cm in size (range 0.6-15 cm). Histologically, renal oncocytoma was composed of an exclusive or predominant component of acidophilic cells with three architectural patterns of disposition: (a) The "classic" pattern (57.5%), composed of a characteristic nested or organoid arrangement of cells, each surrounded by a distinct reticulin framework; (b) a "tubulocystic pattern" (6.3%) with numerous closely packed cystically dilated tubular structures; and (c) "mixed pattern" (36.2%), which had both the organoid and tubulocystic patterns. A gross or microscopic scar was noted in 53.8% cases, and histologically a distinctive myxoid and/or hyalinized stroma separated nests of cells. Generally, the nuclei of renal oncocytoma were round with uniform nuclear contours. Nearly half of the tumors had prominent nucleoli (42.5% had prominent nucleoli equivalent to Fuhrman's grade III or IV). Pleomorphism was absent in 50% of cases but was conspicuous in 12.5% of cases including foci of bizarre cells. Other atypical features included perinephric fat involvement (11.3%), renal parenchymal invasion not associated with desmoplasia (10%), and hemorrhage (31.3%). Renal oncocytoma by definition lacks areas of clear cell carcinoma, significant lesional necrosis, or conspicuous papillary formations. Ancillary features noted included normal-appearing renal tubules within the lesion (15%), intranuclear holes (20%), psammoma bodies (7.5%), and foam cells (7.5%). 15% of tumors were locally excised, and 85% resulted in radical nephrectomy. Mean follow-up of 7.6 years (range 15-200 months) showed no evidence of recurrence, metastasis, or death due to tumor. In conclusion, renal oncocytoma, herein described, is a benign neoplasm and therefore does not merit a nuclear grading scheme. It has unique histologic features including an organoid and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some atypical findings including nuclear pleomorphism, prominent nucleoli, and adjacent renal parenchymal and perinephric fat involvement.

Histologic Correlates of Progression-Free Interval and Survival in Ovarian Clear Cell Adenocarcinoma

Unlike other ovarian epithelial cancers, histologic measures of differentiation of ovarian clear cell adenocarcinoma have not been found to be reliable predictors of progression-free interval and survival. Forty-two consecutively treated patients with pure ovarian clear cell adenocarcinoma were identified and all histologic materials were reviewed. The following histologic features were assessed: architectural pattern (tubular/tubulocystic, papillary, solid, and mixed), average and maximal mitotic activity per 10 high-power fields (hpf's), percentage of cells with clear cytoplasm, and nuclear grading (both Fuhrman et al.'s (Am. J. Surg. Pathol. 6, 655-663, 1982) and Christopherson et al.'s (Cancer 49, 1511-1523, 1982) methods). Surgical stage was most predictive of survival (P < 0.01) and subsequent comparisons using Cox proportional hazards modeling were adjusted for Stages III and IV. Greater than six mitotic figures per 10 hpf's predicted a poorer survival (P = 0.05) but was not predictive of progression-free interval (P = 0.28). Survival and progression-free interval in patients with tumors of mixed architectural pattern tended to be shorter than those for patients where one type did predominate, but this was not statistically significant (P = 0.06). The tubulocystic pattern was not predictive of patient outcome nor was either method of nuclear grading. Stage and average mitotic activity seem to be the best predictors of survival for patients with ovarian clear cell adenocarcinoma, while architectural pattern and nuclear grading are not as reliable.