Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276)

Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC‐derived cell lines and none is well characterized. This study characterizes a novel ChRCC‐derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy‐neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small‐molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid‐differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.     

Rhabdoid differentiation of chromophobe renal cell carcinoma

AIMS: Rhabdoid change represents an aggressive form of divergent differentiation previously reported in conventional (clear-cell) and papillary renal cell carcinoma. This study aims to characterise rhabdoid differentiation in a case of chromophobe renal cell carcinoma (ChRCC) and to investigate its origin by genetic analysis. METHODS: A large tumour mass arising in the right kidney of a 76-year-old male was investigated using routine stains (H&E, Hale's colloidal iron), immunostains (vimentin, cytokeratin) and genetic analysis for loss of heterozygosity (LOH) on chromosomes 1, 2, 3p, 6q, 10q, 13q, 17q, 17p and 21q. RESULTS: The tumour mass was comprised of the following histological subtypes: (i) typical ChRCC, (ii) eosinophilic variant ChRCC and (iii) rhabdoid variant RCC. Tumour cells of all three different histological subtypes had a positive reaction to Hale's colloidal iron stain, negative immunostaining for vimentin and LOH on chromosomes 2, 10q, 13q and 17p. These results are consistent with a diagnosis of ChRCC and indicate a common genetic origin for all three histological cell types. CONCLUSIONS: This study confirms that the aggressive rhabdoid variant can arise from ChRCC, as has been previously demonstrated for conventional (clear-cell) and papillary RCC.     

Histologic prognostic markers for renal cell neoplasia

Although numerous histologic prognostic parameters have been investigated for RCC, those with clinical utility are very limited in number. Tumour morphotype is of prognostic significance. Chromophobe RCC has a more favourable outcome than clear cell and papillary RCC, which in turn is associated with a more favourable outcome than collecting duct RCC. Both clear cell tubulopapillary and tubulocystic RCC appear to have an excellent prognosis. The presence of sarcomatoid or rhabdoid differentiation is a marker of poor prognosis, with sarcomatoid change being associated with median survivals of <18 months. The recently described ISUP/WHO grading system, based upon nucleolar prominence (grade 1–3) and the presence of extreme pleomorphism, sarcomatoid and/or rhabdoid differentiation (grade 4) has been correlated with outcome for clear cell and papillary RCC. It is recommended that chromophobe RCC not be graded. Microscopic coagulative necrosis is a marker of decreased survival, while microvascular invasion is an emerging prognostic parameter.     

Hepatoid differentiation in renal cell carcinoma: a rare histologic pattern with clinical significance

Hepatoid adenocarcinoma is a rare extrahepatic aggressive tumor defined by morphologic and immunohistochemical evidences of hepatoid differentiation. In this study, clinicopathologic features of 3 cases of hepatoid renal cell carcinoma (RCC) were analyzed. Case I was a 53-year-old man with stage III, with 1,460 ng/ml of serum alpha-fetoprotein (AFP) and a 12 cm-sized stage III RCC, which was a combined clear cell and papillary RCC type 2 with sarcomatoid dedifferentiation. Case II was a 62-year-old woman with stage IV, 6.5-cm clear cell RCC and 40,800 ng/mL of serum AFP. Case III was a 51-year-old woman with stage I, 1.6-cm Xp11 translocation RCC and 313.3 ng/mL of serum AFP. Cases I and II died of the disease at 26 and 21 months after radical nephrectomy, respectively. Case III was alive without the disease for 20 months at the last follow-up. Microscopically, three cases show hepatoid carcinoma areas with eosinophilic to clear cells, arranged in trabeculae, separated by thin sinusoidal vessels, in addition to diagnostic features of corresponding RCC subtypes. The tumor cells in these hepatoid carcinoma areas as well as at least focally in RCC areas were immunopositive for AFP in all three cases, but were immunonegative for other hepatic markers (Hep Par1, polyclonal CEA, and glypican 3). This report suggests that the hepatoid features with AFP production are aberrant differentiation that can be developed in various RCC subtypes. Recognizing hepatoid RCC will help explain abnormal elevation of serum AFP levelS, which can be used as a serum surveillance marker.     

Breast carcinoma with choriocarcinomatous features

Although breast carcinomas have been shown to produce various ectopic substances, including human chorionic gonadotropin, it is rare to identify morphologic differentiation compatible with the hormone produced by a tumor. Presently, only eight cases of breast carcinoma with focal choriocarcinomatous differentiation have been reported in the literature. This article describes the pathologic findings, immunohistochemical profile, and clinical course in two additional cases of this unusual variant of breast carcinoma. In the first case, the tumor had morphologic features suggestive of medullary carcinoma, and the patient is doing well 12 months after presentation. In the second case, the tumor was locally advanced at presentation with histologic features consistent with metaplastic carcinoma having squamous, sarcomatoid, and choriocarcinomatous elements. The patient presented with extensive multifocal metastases 6 months after the initial presentation and is not responding well to standard or experimental treatment regimen. Immunostaining for the beta subunit of human chorionic gonadotropin was localized mostly, but not entirely, to multinucleated syncytiotrophoblast-like giant cells within both tumors.     

Anaplastic and sarcomatoid carcinoma of the small intestine: a clinicopathologic study

Carcinomas involving the jejunum and ileum are rare tumors. During a review of small intestinal neoplasms, six primary carcinomas of jejunum or ileum with an anaplastic and sarcomatoid histology were identified. At presentation, three of the patients had symptoms related to metastatic disease and three had symptoms referable to the local tumor. The tumors were large (greater than 4.5 cm in diameter), usually endophytic masses composed of large cells with eosinophilic cytoplasm, anaplastic nuclei, and prominent nucleoli. In many areas, the cells had a spindled configuration. Mucin positivity was identified in all six cases. Electron microscopic findings in two cases were indicative of epithelial differentiation. The tumors behaved aggressively; all five patients for whom there was clinical follow-up died of metastases within 40 months. The six anaplastic and sarcomatoid carcinomas were compared with 29 typical adenocarcinomas arising in the jejunum or ileum. Only two of the latter group had symptoms referable to distant metastases at presentation. These tumors also tended to be smaller at presentation (11 tumors were less than 4 cm in greatest dimension). Of 25 patients with typical adenocarcinomas who had acceptable follow-up, 18 (72%) died of disease and five (20%) were alive with no evidence of disease after 5 years. We conclude that anaplastic and sarcomatoid carcinoma is a rare variant of small intestinal carcinoma with an aggressive clinical course.     

Gastric mixed adenoneuroendocrine carcinoma: correlation of histologic characteristics with prognosis

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.     

Peritoneal washing cytology findings of disseminated myxoid leiomyosarcoma of uterus: report of a case with emphasis on possible differential diagnosis

We report the cytology findings of a rare case of myxoid leiomyosarcoma of the uterus with intraabdominal dissemination. The cytology showed uniformly dispersed spindly to polygonal "epithelioid" tumor cells focally linked by background matrix. Spindly tumor cells attaching to and radiating from branching capillary structures were also present. Occasionally, scattered "signet-ring" cells were found, mimicking metastatic poorly differentiated adenocarcinoma. The background mucoid substance was more conspicuous in the cell block sections. Gross and histologic examination of the surgical specimen revealed a large uterine leiomyosarcoma with prominent myxoid change. Ultrastructural study showed that the "signet-ring" appearance was mainly due to degenerative cytoplasmic change with ballooning of mitochondria, dilatation of endoplasmic reticulum, and elevation of outer nuclear membrane. In contrast to other spindle cell malignancies such as sarcomatoid mesothelioma, sarcomatoid carcinoma, or malignant melanoma, true sarcoma cells in general carry a distinctive cytologic appearance in washing/effusion fluid. In a correct clinical setting, the peculiar association with mucoid matrix and absence of classic lipoblasts should also raise the suspicion of metastatic myxoid leiomyosarcoma.     

Onkozytom versus chromophobes Nierenkarzinom

The differentiation of oncocytic tumors of the kidneys is often difficult, particularly in renal biopsies. Differential diagnoses are chromophobe renal cell carcinoma (ChRCC), renal oncocytoma (RO), the oncocytic variant of papillary renal cell carcinoma (OPRCC), the eosinophilic variant of clear cell renal cell carcinoma (CCRCC) and hybrid oncocytic chromophobe tumors (HOCT). In difficult cases that cannot be resolved by morphology alone, immunohistochemistry is usually helpful. The RO and ChRCC show positive reactions for CD117, they are negative for vimentin and alpha-methylacyl-CoA racemase (AMACR), while CCRCC are positive for vimentin and OPRCC are positive for AMACR. To distinguish between RO and ChRCC, CK7, claudin-7 (both strongly positive in ChRCC and negative or patchy positive in RO) and epithelial cell adhesion molecule (EpCAM) can be used (positive in ChRCC, negative in RO); however, a diagnosis may remain difficult in some cases even with the use of immunohistochemistry. Thus, numerous new methods are being developed in the field of molecular pathology and computer-based morphometric tumor analysis; however, these new methods have not yet been applied in routine diagnostics.     

Mucinous tubular and spindle cell carcinoma of kidney without sarcomatoid change showing metastases to liver and retroperitoneal lymph node

Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon, newly recognized tumor that in its classic histological form shows tightly packed, elongated tubules with transition into spindle cell areas and pale mucinous stroma. The current data suggest that the great majority of MTSCCs have a favorable prognosis; however, the follow-up data are limited and the full biologic potential of this tumor remains to be established. There are a few examples of MTSCCs metastatic to lymph nodes and rare cases with sarcomatoid differentiation associated with distant metastases. We report on a case of MTSCC of kidney with concurrent nodal and liver metastases. The metastatic nodules were well circumscribed and showed morphological and immunophenotypic features similar to those of the primary tumor. Extensive sampling revealed no evidence of sarcomatoid morphology. To our knowledge, this is the first case of MTSCC without sarcomatoid differentiation showing parenchymal metastasis.     

Mucinous tubular and spindle cell carcinoma with aggressive histomorphology--a sarcomatoid variant

Mucinous tubular and spindle cell carcinoma (MTSCC) is a recently described renal epithelial tumor. The bland cytomorphology of the spindled component and low-grade behavior help in its differentiation from sarcomatoid renal carcinoma. Sarcomatoid change has been reported in most histologic variants of renal cell carcinoma apart from MTSCC. Herein we report a case of an MTSCC in a 72-year-old female patient with high-grade spindled areas resembling fibrosarcomatous and undifferentiated pleomorphic sarcoma patterns with metaplastic bone. This index case also demonstrates a high proliferation index and extensive necrosis representing the first documented case of sarcomatoid change in MTSCC.     

Epithelial differentiation in medulloblastoma: comparison with other embryonal tumors of neuroectodermal origin

Three cases of medulloblastoma characterized by epithelial differentiation are described in patients 6-months-, 1-month- and 8-years-old. Histologically, tumors from the two infant patients showed a perivascular arrangement without apparent radiated cytoplasmic processes from the vessels. Tumor cells displayed round and/or pleomorphic vesicular nuclei and a more abundant eosinophilic cytoplasm than that found in classic medulloblastoma. Neither Homer-Wright rosettes nor ependymal or ependymoblastic rosettes were noted in these tumors. The tumor in the 8-year-old patient exhibited a classic medulloblastoma component intermingled with abundant eosinophilic cytoplasm forming a tubular structure. Immunohistochemically, tumor cells in all cases were positive for cytokeratin, synaptophysin, and vimentin. In the third case involving the 8-year-old patient, epithelial tumor cells were positive for cytokeratin, whereas classic medulloblastoma components were negative for cytokeratin. Positive staining for melanoma-specific antigen was seen only in the third case, where strong reactivity of tumor cells formed a tubulus. However, the classic medulloblastoma component was negative for melanoma-specific antigen. Ultrastructurally, basal laminae were observed around tumor cells in the 6-month-old patient. These morphological and immunohistochemical features suggest that medulloblastoma with epithelial differentiation is a rare but distinct variant of medulloblastoma, and that some of these tumors should show differentiation in ocular pigment epithelium.     

甲状腺呈胸腺样分化癌病理观察

目的 探讨甲状腺呈胸腺样分化癌（CASTLE）的病理特征、诊断及鉴别诊断。方法 分析2例甲状腺CASTLE的临床表现,对标本进行病理学和免疫组织化学（EnVision^TM法）染色观察。结果 大体检查肿瘤呈质硬灰白色略旱分叶状肿块。光镜下肿瘤组织呈轮廓清楚的巢状,巢间可见丰富的促结缔组织增生性间质。肿瘤细胞呈多边形或梭形,胞质轻度嗜酸,核卵圆形,呈空泡状,有清楚的小核仁,核异型性较轻,核分裂象1～2／10HPF。免疫组织化学肿瘤细胞表达CD5及CD117。结论 CASTLE是一种少见的甲状腺恶性肿瘤,有一定的病理学特征。应与甲状腺未分化癌、甲状腺鳞状细胞癌、转移性淋巴上皮瘤样癌及滤泡树突细胞肉瘤等鉴别。免疫组织化学CD5等标记对鉴别诊断有帮助。     

High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants.

A clinicopathologic study of 108 cases of high-grade urothelial carcinomas of the renal pelvis is presented. Of the 108 tumors, 44 (40%) showed unusual morphologic features, including micropapillary areas (four cases), lymphoepithelioma-like carcinoma (two cases), sarcomatoid carcinoma (eight cases, including pseudoangiosarcomatous type), squamous differentiation and squamous cell carcinoma (15 cases), clear cells (two cases), glandular differentiation (two cases), rhabdoid, signet-ring or plasmacytoid cells (four cases), pseudosarcomatous stromal changes (four cases) and intratubular extension into the renal pelvis (three cases). Pathological staging was available in 62 patients; of these, 46 cases (74%) were in high stage (pT2-pT4) and 16 (26%) were in low stage (pTis, pTa, pT1). Clinical follow-up ranging from 1 to 256 months (median: 50 months) was available in 42 patients; of these, 26 (61%) died of tumor with a median survival of 31 months. The patients who did not die of their tumors showed only minimal or focal infiltration of the renal parenchyma by urothelial carcinoma, whereas those who died of their tumors showed massive infiltration of the kidney by the tumor. High-grade urothelial carcinomas of the renal pelvis can show a broad spectrum of histologic features similar to those seen in the urinary bladder. Our results support the finding that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are of high histologic grade and present in advanced stages. Our study further highlights the fact that, in the renal pelvis, urothelial carcinomas show a tendency to frequently display unusual morphologic features and metaplastic phenomena. The importance of recognizing these morphologic variants of urothelial carcinoma in the renal pelvis is to avoid confusion with other conditions. The possibility of a high-grade urothelial carcinoma should always be considered in the evaluation of a tumor displaying unusual morphologic features in the renal pelvis, and attention to proper sampling as well as the use of immunohistochemical stains will be of importance to arrive at the correct diagnosis.     

Identification of Three Molecular and Functional Subtypes in Canine Hemangiosarcoma through Gene Expression Profiling and Progenitor Cell Characterization

Canine hemangiosarcomas have been ascribed to an endothelial origin based on histologic appearance; however, recent findings suggest that these tumors may arise instead from hematopoietic progenitor cells. To clarify this ontogenetic dilemma, we used genome-wide expression profiling of primary hemangiosarcomas and identified three distinct tumor subtypes associated with angiogenesis (group 1), inflammation (group 2), and adipogenesis (group 3). Based on these findings, we hypothesized that a common progenitor may differentiate into the three tumor subtypes observed in our gene profiling experiment. To investigate this possibility, we cultured hemangiosarcoma cell lines under normal and sphere-forming culture conditions to enrich for tumor cell progenitors. Cells from sphere-forming cultures displayed a robust self-renewal capacity and exhibited genotypic, phenotypic, and functional properties consistent with each of the three molecular subtypes seen in primary tumors, including expression of endothelial progenitor cell (CD133 and CD34) and endothelial cell (CD105, CD146, and α_vβ₃ integrin) markers, expression of early hematopoietic (CD133, CD117, and CD34) and myeloid (CD115 and CD14) differentiation markers in parallel with increased phagocytic capacity, and acquisition of adipogenic potential. Collectively, these results suggest that canine hemangiosarcomas arise from multipotent progenitors that differentiate into distinct subtypes. Improved understanding of the mechanisms that determine the molecular and phenotypic differentiation of tumor cells in vivo could change paradigms regarding the origin and progression of endothelial sarcomas.Similar to most cancers, sarcomas are classified based on their histologic appearance, which presumably reflects the cells of origin and their capacity for differentiation. These morphologic diagnoses are likely complicated by multiple genomic alterations, microenvironmental differences, and recruitment of nonneoplastic cells into the tumor microenvironment. As a result, the phenotype of the tumor bulk may not reflect the tumor progenitor population, a possibility that has clinical implications in terms of diagnostic criteria and therapeutic approaches.Such morphologic heterogeneity is a feature of canine hemangiosarcoma, a frequent and highly metastatic tumor in dogs that can arise in any organ but that shows predilection for the spleen, right atrium/auricle, and skin or subcutis.¹ The histologic appearance of hemangiosarcomas ranges from the classic cavernous tumor containing neoplastic endothelial-like cells to solid lesions that cannot be distinguished from other soft-tissue sarcomas without the aid of immunohistochemical analysis.² Recent findings have challenged the presumed endothelial ontogeny of canine hemangiosarcomas and the histologically similar human angiosarcomas, suggesting instead that these tumors arise from bone marrow progenitor cells that can transit to peripheral vascular sites.^3–5 Therefore, a more precise identification of hemangiosarcoma progenitors may provide a better understanding of disease progression toward the observed endothelial lineage phenotype.The low incidence and large phenotypic and genetic diversity of human sarcomas hampers understanding of their cellular ontogeny. However, because domestic dogs develop sarcomas spontaneously and with high incidence, the study of canine tumors provides a powerful model in which tumor heterogeneity is maintained. Furthermore, the similarities between human and canine sarcomas make dogs a valuable resource for therapeutic development⁶ and investigations into sarcoma cellular ontogeny. Although it has been suggested that mesenchymal stem cells (MSCs) are the cells of origin for sarcoma,^7,8 there is ongoing debate regarding the potential for other cells to give rise to sarcomas and other tumor types.⁹ Thus, knowledge of progenitor cell populations capable of giving rise to a particular tumor type is useful to positively impact therapeutic design and clinical outcomes.For this study, we tested the hypothesis that hemangiosarcomas arise from multipotent hematopoietic progenitors and that this multipotency is associated with the observed tumor heterogeneity. We identified three distinct molecular subtypes of hemangiosarcoma associated with angiogenesis or endothelial cell development and function (group 1), inflammation and myeloid differentiation and function (group 2), and adipogenesis and lipid transport pathways (group 3). Furthermore, we demonstrate that a subset of cells derived from hemangiosarcoma cell lines show the capacity to recapitulate each of these patterns in vitro. Thus, these results suggest that hemangiosarcoma progenitors contribute to tumor complexity and reflect the array of histologic phenotypes seen. These results also alter the paradigm regarding the origin and progression of canine hemangiosarcoma and suggest that diagnostic and therapeutic approaches addressing progenitor cell biology, rather than the morphologic or histologic appearance of the tumor, need to be developed for this disease.     

Malignant phyllodes tumor of the prostate. A case report with immunohistochemical and ultrastructural studies.

Phyllodes tumor of the prostate is a rare neoplasm with cellular or sarcomatoid stroma and hyperplastic glands. This lesion shares many histologic features with cystosarcoma phyllodes of the breast. Although a malignant variant of phyllodes tumor of the prostate has been described, the majority of cases have been clinically benign. We report an unusual case of phyllodes tumor of the prostate in which the stromal component underwent malignant degeneration, a finding not previously described (to our knowledge). Immunohistochemical and ultrastructural studies demonstrated smooth-muscle differentiation of the stromal cells.     

Diagnostic problems in precancerous lesions and invasive carcinomas of the penis

Penile precancerous and invasive lesions exhibit a variegated morphology. Although the diagnosis and classification of penile tumors is straightforward in most cases, a few entities are problematic, especially to pathologists from countries in which penile cancer is rarely encountered. The differential diagnosis of squamous hyperplasias from differentiated penile intraepithelial neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic and verrucous carcinomas) may be particularly difficult. Similarly, given the morphologic features shared by all verruciform tumors (ie, verrucous, warty, papillary, and cuniculatum carcinomas, along with giant condylomas), it is challenging at times to distinguish one from another. At the other end of the spectrum, because of their lack of differentiation, it is sometimes difficult to classify high-grade carcinomas, such as basaloid and sarcomatoid, which may have etiologic/prognostic implications. Penile mixed tumors, harboring more than 1 histologic subtype and grade, constitute a frequent finding in routine pathology. The recognition of distinctive morphologic patterns and histologic grades in these tumors is important because these features could be related to etiologic factors, such as human papillomavirus infection, or they could influence outcome. Penile tumors with glandular features (eg, adenosquamous and mucoepidermoid carcinomas), although rare, may be confused with the more common pseudoglandular (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker. In this review we provide clues that may help in the differential diagnosis of these lesions.     

Chondroblastoma: varied histologic appearance,potential diagnostic pitfalls,and clinicopathologic features associated with local recurrence

Chondroblastoma is a rare, benign bone tumor. Although it has distinctive clinicopathologic features, its wide morphologic spectrum may pose diagnostic problems. We present the clinicopathologic features of 42 patients (28 males, 14 females; age range, 8 to 66 years), with emphasis on unusual histologic features, potential diagnostic pitfalls, and factors associated with recurrence. Thirty-four tumors were in long bones, with the most common site being the proximal femur. Unusual histologic features included the presence of atypical, epithelioid, spindle, and foamy cells and necrosis and a diffuse basophilic myxoid matrix. Tumors with focal osteoclast-like giant cell rich areas (n = 11), prominent cystic change (n = 8) and extensive fibromyxoid areas (n = 3) resembled giant cell tumors, aneurysmal bone cysts, and chondromyxoid fibromas, respectively. The diagnosis of referring pathologists was inaccurate in 34% of cases. Six patients (14%) had local recurrence. The only clinical feature significantly associated with increased risk of local recurrence was duration of symptoms for less than 6 months (log rank P =.003). None of the histologic features was significantly associated with recurrence. These included worrisome features such as cellular atypia, necrosis, and mitoses. None of the patients had metastases. An increased awareness of the morphologic spectrum of chondroblastomas will enable pathologists to avoid diagnostic pitfalls. We emphasize the need for a combined clinical, radiologic and histologic approach to the diagnosis of chondroblastomas.     

Low-grade myxoid renal epithelial neoplasms with distal nephron differentiation

We report 4 distinctive renal epithelial neoplasms that are essentially identical at the morphologic and immunohistochemical levels and do not fit an accepted category in the existing classification of these lesions. The patients were all females, with ages ranging from 32 to 79 years (mean, 50 years). The tumors were well circumscribed and were composed of uniform, predominantly low cuboidal cells with eosinophilic, focally vacuolated cytoplasm. Tumor cells generally formed interconnecting tubules, with smaller areas of cordlike growth and spindling in a bubbly, myxoid stroma. All tumors were confined to the kidney, and all were immunoreactive for high-molecular-weight cytokeratin 34betaE12, cytokeratin 7, epithelial membrane antigen, and cytokeratin cocktail AE1/3. Only 1 tumor was focally immunoreactive for Ulex europaeus agglutinin. Ultrastructural study showed tumor cells forming tubular structures reminiscent of the loop of Henle or distal convoluted tubule. Follow-up in all 4 cases was benign. These distinctive tumors may be confused with aggressive sarcomatoid renal cell carcinomas because of their spindled morphology. The morphologic, immunohistochemical, and ultrastructural features of these lesions indicate differentiation toward distal nephron segments. Similar tumors probably have been reported among low-grade collecting duct carcinomas or tumors "possibly related to the loop of Henle."