Metanephric adenoma of the kidney with massive hemorrhage and necrosis: immunohistochemical, ultrastructural, and flow cytometric studies

Metanephric adenoma of the kidney is rare. We report 2 cases of metanephric adenoma with massive hemorrhage and necrosis. Case 1, a 42-year-old Japanese woman, complained of abdominal pain. Case 2, a 41-year-old Japanese woman, complained of fever and lumbago. They underwent nephrectomy. The cut surface was solid and yellow with massive hemorrhage and necrosis. These tumors showed packed tubular and glomeruloid patterns. The tumor cells were uniform and small, with uniform, oval, and hyperchromatic nuclei and scant cytoplasm, and showed reactivity for cytokeratin, vimentin, and CD 57. The MIB-1 indexes were up to 0.63%. The DNA ploidy pattern was diploid. The tumor cells formed small tubular structures with lumina and microvilli. These features suggested that metanephric adenoma is a benign tumor of an immature epithelial nature.     

S100 protein expression distinguishes metanephric adenomas from other renal neoplasms

Metanephric adenoma is a benign renal neoplasm with morphologic features similar to those of malignant renal neoplasms, such as papillary renal cell carcinoma (RCC) and Wilms' tumor. Different methods have been used to distinguish between metanephric adenoma and papillary RCC and Wilms' tumor. However, some techniques are not always available, such as certain immunohistochemical stains, cytogenetics, molecular genetics, and electron microscopy. In the current study, we compared the expression of S100 protein in 15 cases of metanephric adenoma, 10 cases of Wilms' tumor, and 13 cases of papillary RCC. Our results revealed strong expression of S100 proteins in all cases of metanephric adenoma, weak expression in two cases of Wilms' tumor, and no expression in any of the cases of papillary RCC. These findings indicate that S100 could be a useful and accessible tool for the diagnosis of metanephric adenoma.     

Multifocal metanephric adenoma in childhood

Metanephric adenoma is the most commonly occurring member of the metanephric tumor family, which also includes metanephric adenofibroma and metanephric stromal tumor. According to the World Health Organization classification, however, it is not commonly multifocal. Reported herein is the case of a 9-year-old boy with multifocal metanephric adenoma. Histologically, surgical sections showed multifocal proliferation of small rounded and uniform cells with smooth nuclear contours, scant pale-staining cytoplasm, dark-staining nuclei, and inconspicuous nucleoli: the cells were arranged in sheets and acinal, ductal, glomeruloid, and papillary structures. On immunohistochemistry the tumor cells were positive for vimentin, cytokeratins (CAM5.2, AE1/AE3, and CK18), and WT1, but negative for cytokeratin 7 (CK7) and epithelial membrane antigen (EMA). The Ki-67 labeling index was <1%. In addition, cytogenetic analysis indicated a normal karyotype (46XY). Other histologically similar tumors are papillary renal cell carcinoma and nephroblastoma, and it is necessary to distinguish metanephric adenoma from those tumors because of malignancy. In contrast to those tumors, metanephric adenoma has inconspicuous nucleoli, loss of CK7 and EMA expression, and no mitotic figures. Thus, the histological and immunohistochemical features of the present case were compatible with metanephric adenoma.     

Fine‐needle aspiration of metanephric adenoma of the kidney with clinical,radiographic and histopathologic correlation: A review

Metanephric adenoma of the kidney is an uncommon benign epithelial neoplasm with only a small number of reports that describe its cytologic features. We describe two additional cases of metanephric adenoma diagnosed on fine‐needle aspiration biopsy and review the available literature. Our cases showed similar cytology and were composed of cellular smears with numerous clusters of small, oval to round cells arranged in a microfollicular pattern and papillary configurations. The tumor cells had scant cytoplasm, fine chromatin and absent nucleoli. Psamomma bodies, nuclear atypia, cellular cpleomorphism, necrosis, and mitoses were absent. Because of the rarity of this tumor and the common cytologic features it shares with other lesions, including malignant tumors such as Wilms’ tumor and papillary renal cell carcinoma, awareness of the cytologic features of metanephric adenoma may aid in avoiding a diagnosis of malignancy, especially preoperatively, and in guiding the proper management for the patients. Diagn. Cytopathol. 2013;41:742–751. © 2013 Wiley Periodicals, Inc.     

Passive seeding in metanephric adenoma: a review of pseudometastatic lesions in perinephric lymph nodes

Lymph node involvement derived from a discrete neoplastic process fundamentally implies tumor malignancy. However, rarely, inconsequential passive transport of benign neoplastic cells to the lymph node can occur and may cause confusion as to the nature of the neoplasm (ie, malignant vs benign). We describe a 10-cm right renal metanephric adenoma incidentally discovered in a 30-year-old woman during cesarean section for a triplet pregnancy. Subsequent nephrectomy following an equivocal needle biopsy diagnosis showed histologic features classic for metanephric adenoma, including the lack of cytologic atypia and mitoses. Necrosis present in this lesion appeared to be secondary to tumor physical disruption. The tumor cells were positive for Wilms tumor 1 (WT1) antigen, pankeratin, and CD57, focally positive for epithelial membrane antigen, and negative for cytokeratin 7, cytokeratin 34betaE12, and CD56. Electron microscopy confirmed the tumor's epithelial nature, and cytogenetics revealed a diploid 46XX karyotype. The tumor proliferation index with Ki-67 was only 3% to 5% and the proliferating cell nuclear antigen index was 0%. A single, concurrently resected hilar lymph node contained scattered subcapsular, sinusoidal, and focally intralymphovascular psammoma bodies along with occasional adherent epithelial cells. These cells were highlighted by pankeratin but were nonreactive to WT1 antigen, similar to the nonviable cells in the primary tumor. Clinical surveillance and follow-up showed no disease recurrence 4 years after nephrectomy. We postulate that the lymph node inclusions found in this case represent passive transport of neoplastic cells to the lymph node following manipulation of the renal mass. We conclude that this phenomenon is understudied and underrecognized and can easily be mistaken for metastasis.     

Diagnosis of renal metanephric adenoma: relevance of immunohistochemistry and biopsy

Most renal tumors of the adult are carcinomas. Their treatment is surgical, consisting of limited excision or nephrectomy. In some instances, biopsy of the tumor can be performed in order to adapt treatment. We report the case of a 45 year-old woman presenting with renal tumor. A biopsy of the mass showed a metanephric adenoma. No surgical excision was performed because of the benignity of this tumor. Here we develop the interest of immunohistochemistry for differential diagnosis of metanephric adenoma and other "basophilic small cell tumors" of the kidney. We also put the stress on the growing role of biopsy of renal tumor allowing optimal treatment.     

Metanephric adenoma and papillary carcinoma with sarcomatoid dedifferentiation of kidney. A case report

We present the case of a 74-year-old Caucasian male with an expansive process of the left kidney. No clinical and laboratory signs of polycytemia or hypertension were present. Microscopically, the spherical main tumor mass was composed of small basophilic cells arranged in longitudinal branching tubules typical of metanephric adenoma (MA). Another component, different from MA, was formed by a tumor in a papillary and tubopapillary arrangement. This component was diagnostic of grade 3 papillary renal cell carcinoma. The third component, which was merging with the papillary one, was composed of sarcomatoid, spindle cell carcinoma with prominent nuclear polymorphism and a high number of mitotic figures, including atypical mitoses. The sarcomatoid component filled the entire cortico-medullary space and infiltrated the surrounding non-neoplastic renal tissue, including the renal pelvis. Areas of necroses, hemorrhages, and mitotic figures were frequent. No structures of Wilm's tumor were seen in our case. One year after the excision, the patient is without recurrence and metastasis. The existence of the above mentioned tumor supports the hypothesis that metanephric adenomas and papillary renal cell carcinomas are interrelated lesions.     

Recent classification of renal epithelial tumors

The recent classification of renal tumors is based on genetic evidence as well as on histologic features. Malignant tumor includes clear cell renal carcinoma (RCC), multilocular cystic RCC, papillary RCC, chromophobe RCC, carcinoma of the collecting duct of Bellini, renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and mucinous tubular and spindle cell carcinoma. Benign tumor is subdivided into papillary adenoma, renal oncocytoma and metanephric adenoma. Recently, new disease entities such as acquired cystic disease-associated RCC, clear cell papillary RCC and renal carcinoma with t(6;11)(p21:q12) have been discovered. In this article, we briefly review and introduce the clinical, morphological and genetic features of these tumor entities.     

Metanephric adenoma lacks the gains of chromosomes 7 and 17 and loss of Y that are typical of papillary renal cell carcinoma and papillary adenoma.

Metanephric adenoma has morphologic similarities to papillary renal cell neoplasms. Cytogenetic studies of papillary renal cell carcinoma and papillary adenoma have shown frequent gains of chromosomes 7 and 17 and loss of the Y chromosome. Some cytogenetic studies have supported the hypothesis that metanephric adenoma is related to papillary renal cell neoplasia; others have not. Seven metanephric adenomas were studied with fluorescence in situ hybridization in paraffin sections using centromeric probes for chromosomes 7, 17, and Y diluted 1:100 with tDenHyb1 buffer. The signals in 100 to 200 nuclei were counted in each tumor. Samples of histologically normal renal cortical tubule epithelium were used as controls. In all seven metanephric adenomas, the results for chromosomes 7 and 17 were similar: a high percentage of nuclei with two signals (range, 75 to 85%; median, 79%). Normal kidney showed similar results (range, 78 to 88%; median, 84%). The Y chromosome was present in all three of the tumors from males (range, 86 to 89% of nuclei; median, 87%). Normal kidney gave similar results (range 82% to 91%, median 84%). The presence of chromosomes 7, 17, and Y in metanephric adenomas is similar to their presence in normal kidney. Metanephric adenoma lacks the frequent gains of chromosomes 7 and 17 and losses of the Y chromosome that are typical of papillary renal cell neoplasms, supporting the notion that metanephric adenoma is not related to papillary renal cell carcinoma and papillary adenoma. Genetic analysis of chromosomes 7, 17, and Y may facilitate discrimination of metanephric adenoma from papillary renal cell carcinoma in difficult cases.     

Benign tumors and tumor-like lesions of the adult kidney. Part II: Benign mesenchymal and mixed neoplasms, and tumor-like lesions

In this review article the benign tumors and tumor-like lesions of the adult kidney are discussed. The incidence of benign renal tumors is low, especially when compared to renal cell carcinomas, as most are detected incidentally or at autopsy. Some of these tumors, as their names imply, are unique to the kidney, e.g., renal adenoma, metanephric adenoma, renal oncocytoma, nephrogenic adenofibroma, mesoblastic nephroma, capsuloma, juxtaglomerular cell tumor, renomedullary interstitial cell tumor (medullary fibroma), cystic nephroma, cystic partially differentiated nephroblastoma, and cystic hamartoma of the renal pelvis, while others, such as angiomyolipoma, leiomyoma, hemangioma, lipoma, etc., are not unique to the kidney and show similar morphologic features in the other sites they affect. Of the tumor-like lesions, xanthogranulomatous pyelonephritis, malakoplakia, and renal cysts are the most common. The other entities, such as fibroepithelial polyp, are rare, most having been the topic of case reports. In Part I of this paper the benign epithelial tumors of the kidney were previously discussed. This paper (Part II) is devoted to the benign mesenchymal tumors, mixed mesenchymal and epithelial tumors, and the tumor-like lesions.     

The 2012 ISUP Vancouver and 2016 WHO classification of adult renal tumors: changes for common renal tumors

In the past decade, the histological classification of renal neoplasia has undergone significant changes. Many new entities with distinct clinical, pathological and genetic features have been identified. In addition, common and established tumor entities have been further refined with regard to their pathological and genetic features. These changes have been incorporated in the 2012 International Society of Urological Pathology Vancouver classification and also in the 2016 World Health Organization classification. This article will focus on the new discoveries of clinical, pathological and molecular characteristics of the common renal tumors, including clear cell renal cell carcinoma, multilocular cystic renal neoplasm of low malignant potential, papillary renal cell carcinoma, chromophobe renal cell carcinoma, mucinous tubular and spindle cell renal cell carcinoma, collecting duct carcinoma, renal medullary carcinoma, papillary adenoma, oncocytoma, metanephric tumors, angiomyolipoma, and mixed epithelial and stromal tumor.     

Cytogenetics of papillary renal cell tumors

Chromosome aberrations were determined in short-term cultures of 18 papillary renal cell tumors, as well as in the cell line ACHN, and the results were evaluated together with 20 previously published cases. We found that chromosomes 7, 17, and 16 and the Y chromosome were specifically involved in the karyotype changes, marks benign papillary renal cell adenomas (ten cases). Malignant papillary renal cell carcinomas (29 cases) were characterized by additional trisomies: trisomy 16 occurred in 20 tumors, and trisomy 12 and 20 in 8 tumors each. Loss of the Y chromosome was observed in 7 of 9 benign and in 23 of 25 malignant tumors that developed in males. None of the papillary renal cell adenomas or carcinomas showed a loss of 3p or gain of a 5q segment, both of which are characteristic of common non-papillary renal cell carcinomas.     

后肾性腺瘤3例报道并文献复习

目的：探讨后肾性腺瘤的病理形态学特征及诊断要点。方法：采用常规HE染色及免疫组化染色，并复习文献。结果：组织学上主要由紧密而规则排列 的圆形小管和含有圆形细胞巢的实性区相间排列，偶见肾小球样结构。免疫组化以Leu7、vimetntin、keratin阳性及EMA阴性为特点。结论：后肾性腺瘤是肾胚胎残留发生的罕见良性肿瘤，常被误诊为恶性肿瘤，故与肾母细胞瘤、乳头状肾细胞癌鉴别尤为重要。     

An immunophenotypic comparison of metanephric metaplasia of Bowman capsular epithelium with metanephric adenoma, Wilms tumor, and renal development: a case report and review of the literature

Metanephric metaplasia of the parietal epithelium of the Bowman capsule is a rare pathologic finding of unknown pathogenesis that has occurred in patients with widespread malignant neoplasms of various types. We report this finding in a 25-year-old woman with partial expression of the Carney triad who died of a disseminated gastrointestinal stromal tumor, specifically a gastric stromal sarcoma. The metaplasia involved both kidneys diffusely. It originated in the parietal epithelium of the Bowman capsule, extended into the proximal tubules, and focally surrounded the glomeruli in a semicircular manner Immunohistochemical analysis revealed that the cells of metanephric metaplasia expressed the Wilms tumor gene product, bcl-2 protein, and CD57 and cytokeratin 7 and keratin AE1/AE3 focally, but not CD56. This immunophenotype parallels that of metanephric adenoma, Wilms tumor, and nephrogenic rests and overlaps with antigen expression in certain periods of renal development.     

Renal cancer: cytogenetic and molecular genetic aspects

To date, much progress has been made in the fields of cytogenetics and molecular genetics of renal tumors. The previous and recent findings have delineated the characteristics of the various tumors, particularly the cytogenetic and molecular differences that exist between papillary and nonpapillary clear cell renal cell carcinomas (RCCs). At the same time, new cytogenetic subtypes have emerged [e.g., t(X;1)] in subtypes of RCC, while in others (e.g., Wilms tumors) several new cytogenetic abnormalities and consequent molecular involvement have been found. In addition to Wilms tumor, papillary RCC, and clear-cell RCC, cytogenetic and fluorescence in situ hybridization analyses have been performed on several other tumors of the kidney, including chromophobic carcinoma, metanephric adenoma, collecting duct carcinoma, transitional cell carcinoma, congenital mesoblastic nephroma, and malignant rhabdoid tumors of the kidney. This review is therefore intended to present a concise update on the cytogenetic and molecular data on renal tumors, focusing mainly on the clinical usefulness of the findings reported in the literature.     

Cytologic and fluorescence in situ hybridization (FISH) examination of metanephric adenoma

Metanephric adenoma is a recently described benign renal neoplasm with distinctive histologic features. The cytologic appearance and fluorescence in situ hybridization (FISH) studies of this tumor have not been described. We present a case from a 48-yr-old woman. Cytologically, the cells were arranged in tight, short papillae and loose sheets. The cells had scant cytoplasm, round monotonous nuclei with fine even chromatin and rare small nucleoli. Immunohistochemistry revealed no reactivity for epithelial membrane antigen (EMA), keratins (AE1/AE3, callus, 34BE12), or carcinoembryonic antigen (CEA). FISH showed a disomic pattern for chromosomes 7, 17, and for the chromosome 3 short arm. The differential diagnosis includes Wilms' tumor, renal adenoma, papillary renal cell carcinoma, and metastatic tumors. Both immunohistochemistry and FISH may be of help in distinguishing some of these lesions. Diagn. Cytopathol. 16:107–111, 1997. © 1997 Wiley-Liss, Inc.     

Malignant pleomorphic adenoma (malignant mixed tumor) of the trachea. Report of a case

Malignant pleomorphic adenoma arising in the trachea has not been reported in the literature. We report here a case of malignant pleomorphic adenoma (malignant mixed tumor) occurring in the trachea of a 65-year-old woman. The tumor metastasized to the lung and the chest wall 11 years after complete resection of the primary tumor, which was a polypoid submucosal tumor, 1.3 cm in diameter. Light microscopic examination of the primary and metastatic tumors showed the presence of epithelial and stromal elements, consisting of grandular structures, foci of squamous metaplasia and a myxochondroid stroma. Many tumor cells showed myoepithelial cell features by electron microscopy, and immunoreactivity for S-100 protein and GFAP was also seen in many of them. These findings were consistent with those of pleomorphic adenoma. However, the epithelial elements were cytologically atypical with prominent mitotic figures. Infiltration of the tumor cells into the surrounding soft tissue was also seen. No foci of benign pleomorphic adenoma were found in the primary tumor. These findings indicate that this tumor was not a carcinoma ex pleomorphic adenoma, but a true malignant pleomorphic adenoma (true malignant mixed tumor) of the trachea.     

MALIGNANT PLEOMORPHIC ADENOMA (MALIGNANT MIXED TUMOR) OF THE TRACHEA. Report of a Case

Malignant pleomorphic adenoma arising in the trachea has not been reported in the literature. We report here a case of malignant pleomorphic adenoma (malignant mixed tumor) occurring in the trachea of a 65-year-old woman. The tumor metastasized to the lung and the chest wall 11 years after complete resection of the primary tumor, which was a polypoid submucosal tumor, 1.3 cm in diameter. Light microscopic examination of the primary and metastatic tumors showed the presence of epithelial and stromal elements, consisting of grandular structures, foci of squamous metaplasia and a myxochondroid stroma. Many tumor cells showed myoepithelial cell features by electron microscopy, and immunoreactivity for S-100 protein and GFAP was also seen in many of them. These findings were consistent with those of pleomorphic adenoma. However, the epithelial elements were cytologically atypical with prominent mitotic figures. Infiltration of the tumor cells into the surrounding soft tissue was also seen. No foci of benign pleomorphic adenoma were found in the primary tumor. These findings indicate that this tumor was not a carcinoma ex pleomorphic adenoma, but a true malignant pleomorphic adenoma (true malignant mixed tumor) of the trachea. ACTA PATHOL JPN 38: 1215∼1226, 1988.     

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.     

Differentiated papillary kidney tumors. Differentiation between metanephric adenoma and papillary adenoma

Metanephric adenoma of the kidney is a well described tumor entity. The differential diagnosis between papillary adenoma or papillary carcinoma type 1 and metanephric adenoma of the kidney can be challenging in single cases. We report two cases of metanephric adenomas and compare their immunophenotype with a papillary adenoma. The analysis of these metanephric adenomas and a review of the literature shows that CD-57 positivity and lack of EMA expression are helpful in distinguishing metanephric adenoma from papillary adenoma and papillary carcinoma. Glomeruloid structures, Psammoma bodies, necrosis or expression of cytokeratin 7 and vimentin are common features in metanephric adenoma and papillary adenoma or papillary carcinoma. The knowledge of the immunohistochemical constellation is important, because metanephric adenoma can be very large and often have some necrosis.