A case of tumor-to-tumor metastasis of cutaneous malignant melanoma.

We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6-cm, well-encapsulated left-sided nodule, red-brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor-to-tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre-existing neoplasm.

Essential role of ultrastructural examination for spindle cell oncocytoma: Case report of a rare neoplasm and review of the literature.

Spindle cell oncocytoma (SCO) is an extremely rare neoplasm of the sellar region recognized as a distinct benign histopathological subtype of pituitary tumors in the 2007 World Health Organization classification of tumors of the central nervous system. The morphology of its neoplastic cells (spindle cells and granular eosinophilic cytoplasm) is common to several other lesions so that immunohistochemistry, together with ultrastructural examination, becomes essential in solving this differential diagnosis. Despite being labeled as benign, recurrence is described. Herein, we report a case of SCO in a 77-year-old man and discuss the diagnostic difficulties, ultrastructural aspects, and prognostic factors.

Spindle cell oncocytoma of the pituitary gland with follicle-like component: organotypic differentiation to support its origin from folliculo-stellate cells.

Spindle cell oncocytoma (SCO) is a rare, non-adenomatous tumor originating from the anterior pituitary gland. Composed of fusiform, mitochondrion-rich cells sharing several immunophenotypic and ultrastructural properties with folliculo-stellate cells (FSC), SCO has been proposed to represent a neoplastic counterpart of the latter. To date, however, SCO has failed to meet one criterion commonly used in histological-based taxonomy and diagnostics; that of recapitulating any of FSCs' morphologically defined developmental or physiological states. We describe a unique example of SCO wherein a conventional fascicular texture was seen coexisting with and organically merging into follicle-like arrangements. The sellar tumor of 2.7 × 2.6 × 2.5 cm was transphenoidally resected from a 55-year old female. Preoperative magnetic resonance imaging indicated an isointense, contrast enhancing mass with suprasellar extension. Histology showed multiple rudimentary to well-formed, follicle-like cavities on a classical spindle cell background; while all the participating cells exhibited an SCO immunophenotype, including positivity for S100 protein, vimentin, EMA, Bcl-2, and TTF-1, as well as staining with the antimitochondrial antibody 113-1. Conversely no expression of GFAP, follicular-epithelial cytokeratin, carcinoembryonic antigen, or anterior pituitary hormones was detected. Ultrastructurally, tumor cells facing follicular lumina displayed organelles of epithelial specialization, in particular surface microvilli and apical tight junctions. This constellation is felt to be reminiscent of FSCs' metaplastic transition to follicular epithelium, as observed during embryonic development and physiological renewal of the hormone-secreting parenchyma. Such finding is apt to being read as a supporting argument for SCO's descent from the FSC lineage.

Oncocytoma of the kidney with prominent intracytoplasmic lumina.

Oncocytoma is a histologically distinctive neoplasm of the kidney, with a well-recognized cytoarchitectural appearance. On occasion, however, renal oncocytomas are known to exhibit unusual morphologic features that may pose diagnostic difficulties. We present the clinical and pathologic details of an oncocytoma of the kidney with an unusual histologic appearance imparted by the presence of large numbers of prominent intracytoplasmic lumens. Morphologically, the neoplasm was composed of uniform polygonal cells with copious amounts of granular, eosinophilic cytoplasm, round nuclei, and prominent nucleoli, exhibiting an organoid pattern of growth. Intracytoplasmic lumina of varying size were present throughout the tumor. There were no mitotic figures or areas of necrosis present. The diagnosis of oncocytoma was supported by immunohistochemical and ultrastructural studies. By electron microscopy, the intracytoplasmic lumens appeared as membrane bound spaces with associated microvilli. The presence of intracytoplasmic lumina in a significant proportion of cells is an uncommon feature of renal oncocytoma which can generate problems in diagnosis. Awareness of this phenomenon should allow for improved recognition of oncocytomas exhibiting this type of unusual morphology.

Use of electron microscopy in core biopsy diagnosis of oncocytic renal tumors.

The distinction between oncocytoma and chromophobe renal cell carcinoma, important clinically, may be challenging, especially as the tissue sample size decreases. Ancillary studies can be helpful, although subject to interpretation and sample variability. The aim of this study was to examine the value of electron microscopy in differentiating between oncocytoma and chromophobe renal cell carcinoma on formalin fixed paraffin embedded needle core biopsies. Twenty renal needle core biopsies were evaluated. Despite formalin fixation and paraffin embedding, the classic ultrastructural features of these neoplasms were retained, revealing 80% sensitivity and 100% specificity by initial work-up.

Mitochondria with tubulovesicular cristae in renal oncocytomas.

Renal oncocytoma and chromophobe renal cell carcinoma (CRCC) are closely related tumors. They are considered the extremes of a spectrum with several variants. Ultrastructural examination of the mitochondria is a helpful procedure in the diagnosis of these neoplasms. Renal oncocytomas show mitochondria with piled lamellar cristae, and CRCC exhibited mitochondria with tubulovesicular cristae. In a series of 23 histologically diagnosed renal oncocytomas examined by electron microscopy, the authors found 5 tumors exhibiting more cells with mitochondria showing tubulovesicular cristae. The authors believe these 5 cases present a submicroscopic appearance intermediate between renal oncocytoma and CRCC, although with benign clinical behavior.

Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma: case report with electron microscopic studies.

We report a rapidly recurring folliculostellate cell tumor of the adenohypophysis in a 63-year-old woman. Morphologically the tumor had the typical appearance of a spindle cell oncocytoma of the adenohypophysis. It recurred within 5 months of selective transsphenoidal resection, requiring a second transsphenoidal operation followed by radiation therapy. The spindle cell oncocytoma (SCO) of the adenohypophysis is a relatively recently described entity and a new addition to the fourth edition of the WHO Classification of Tumors of the Central Nervous System. In our case, the ultrastructural features were significantly different from those so far described in SCO, in that tumor cells formed a network of structures indistinguishable from pituitary follicles. In addition, a minority of tumor cells exhibited endocrine differentiation.

Subclinical Cushing's syndrome associated with an adrenocortical oncocytoma.

Oncocytoma is a neoplasm that can arise in several organs, and it has been more commonly described in the kidney, salivary gland and thyroid. Oncocytoma arising in the adrenal gland is a rare finding. Moreover, functioning adrenocortical oncocytoma is exceptionally rare. A 47-yr-old man was incidentally discovered to have a right adrenal mass. The patient had no clinical features suggestive of increased adrenal function. However, hormonal evaluation showed a disturbed cortisol circadian rhythm, supranormal urinary cortisol excretion, a low level of ACTH, and a lack of suppressibility of cortisol secretion after dexamethasone. Right adrenalectomy was performed, and this revealed a well-circumscribed dark-brown tumor that measured 2.4x2.2 cm. The tumor consisted almost exclusively of large eosinophilic and epitheloid cells whose cytoplasm was packed with eosinophilic granulations, which corresponded to the numerous mitochondria confirmed on electron microscopy. This is a rare case of subclinical Cushing's syndrome that was caused by adrenocortical oncocytoma.

Spindle cell oncocytoma of the adenohypophysis: report of two recurrent cases.

The recently described "spindle cell oncocytoma of the adenohypophysis" is a very rare and often misdiagnosed entity. A benign biologic behavior has been suggested based on the absence of recurrences with a median follow-up of 3 years. Herein, we present 2 cases of recurrent spindle cell oncocytomas. One patient is a 71-year-old woman (case no. 1) and the other a 76-year-old man (case no. 2). Recently, both underwent transsphenoidal reexploration for recurrent "pituitary adenoma." Patient no. 1 had initial surgery 11 years ago with a recurrence after 3 years that was initially stable. Ultimately, a partial resection was performed after compression of optic pathways by the tumor, and approximately 1 year later, re-resection was carried out. Patient no. 2 had initial surgery 10 years ago with recurrence and resection after 3 years. He recently presented with a large mass that involved the pituitary fossa and base of the skull, with extension into the nasopharynx and nasal cavity. The primary and recurrent lesions of both cases showed similar architecture with interlacing fascicles of spindle cells that alternated with areas of epithelioid-like cells that exhibited eosinophilic, granular cytoplasm. Neoplastic cells were positive for vimentin, S-100 protein, and epithelial membrane antigen, and negative for glial fibrillary acidic protein, chromogranin, and pituitary hormones. Increased mitotic activity was noted in 1 lesion (case no. 2), although both cases had high Ki-67 indices (18% and 20%, respectively). The ultrastructural features of both cases were characteristic with intracytoplasmic accumulations of large mitochondria. The histopathologic features of these lesions are consistent with spindle cell oncocytoma of the adenohypophysis. In summary, we are reporting 2 cases of recurrent spindle cell oncocytoma of adenohypophysis with longer follow-up than previously published cases, suggesting the possibility of a more aggressive behavior than has been initially considered.

The clinicopathological, ultrastructural, genetic features and diagnosis of small cell variant renal oncocytoma.

The small cell variant renal oncocytoma is until now a rarely described and easily misdiagnosed subtype of renal oncocytoma. The tissue morphology, immunohistochemical profile, ultrastructural and molecular characteristics of four cases of small cell variant renal oncocytoma were analyzed and the literature was reviewed. The patients were three women and one man with ages ranging from 51 to 76 years. The size of the tumors ranged from 3 to 8.5 cm in diameter. The follow-up duration ranged from 6 to 58 months. All patients lived uneventfully without tumor recurrence or metastasis. The tumors were grayish yellow to brown, well demarcated, with a central scar or cystic change. Microscopically, the tumor was arranged in lobular structure containing dense small acini or tubular structures, with small cells featuring weak eosinophilic and scant cytoplasm, small round nuclei and inconspicuous nucleoli. No mitotic figures or necrosis were discerned. The immunohistochemical profile of small cell variant of renal oncocytoma is partially consistent with classic oncocytoma, expressing EMA, CK18, CD117 and E-cad. However, MITO and S-100A1 were intensively expressed in classic RO, but neither of them was expressed in small cell variant RO. Ultrastructurally, a small number of organelles was revealed in the tumor cell, including a few mitochondria, lysosomes and microvilli, less than those in the classic oncocytoma. No genetic aberrations were found in all cases regardless of clinicopathological characteristics and tissue types. Small cell variant renal oncocytoma of the kidney is frequently difficult to be differentiated from other benign and malignant small cell tumors with eosinophilic cytoplasm. The immunohistochemical profile, ultrastructural and genetic features of the tumor are integrally presented here for the first time. Acquaintance with the special characteristics of the tumor could facilitate the correct diagnosis of the tumor.

TTF-1-positive oncocytic sellar tumor with follicle formation/ependymal differentiation: non-adenomatous tumor capable of two different interpretations as a pituicytoma or a spindle cell oncocytoma.

We describe herein the unique case of a 70-year-old male with a TTF-1-positive non-adenomatous sellar tumor that has unusual morphological and immunohistochemical features. MRI examination detected a 2-cm sellar mass that was enhanced heterogeneously. By histology, the tumor was composed of epithelioid and oncocytic cells arranged in a trabecular pattern with occasional luminal structures. The lesion was diffusely immunopositive for thyroid transcription factor-1 (TTF-1) and vimentin but negative for S100 protein and GFAP. Immunoreactivity for epithelial membrane antigen, low molecular weight cytokeratin (CAM 5.2), and neuronal markers was also observed in the tumor cells. By electron microscopy, the tumor cells were filled with abundant mitochondria and extended microvillous projections into small extracellular and intracellular lumens. TTF-1 is considered to be an excellent marker of pituicytes, specialized glia of the neurohypophysis. This case can be regarded as a variant of pituicytoma, showing both ependymal differentiation and oncocytic changes. However, the immunoprofile was not completely consistent with a pituicyte lineage; the epithelial features suggested a possibility of folliculostellate cell origin. TTF-1-positive sellar neoplasms might therefore have variable morphological and immunohistochemical profiles. For suitable classification of TTF-1 positive sellar neoplasms, their histological features should be carefully re-evaluated.

'Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells?

We describe five primary tumors of the adenohypophysis featuring mitochondrion-rich spindle cells. The patient ages ranged from 53 to 71 years (mean 61.6 years); two were female. All presented with panhypopituitarism. Two also had visual field defect. On neuroimaging all tumors showed suprasellar extension and were indistinguishable from pituitary adenoma. None showed imaging or operative evidence of dural involvement. All were gross totally removed: four by transsphenoidal surgery and one by frontal craniotomy. Follow-up ranged from 2 to 68 months (mean 35.4 months). No recurrences were noted. The clinical workup was noncontributory in all but two patients: one (case no. 4) with an oncocytic thyroid adenoma and another (case no. 5) with squamous carcinoma of both the uterine cervix and of vocal cord. Histologically, the five tumors were composed mainly of fascicles of spindle cells with eosinophilic, granular cytoplasm. Mitoses were rare and necrosis was absent. Neoplastic cells were immunoreactive for vimentin, epithelial membrane antigen, S-100 protein, and galectin-3. Stains for pituitary hormones, synaptophysin, chromogranin, glial fibrillary acidic protein, cytokeratin CAM5.2, smooth muscle actin, CD34, and CD68 were negative. No thyroglobulin immunoreactivity was noted in the tumor of case no. 4. Ultrastructurally, the neoplastic cells contained numerous mitochondria with lamellar cristae. The neoplastic cells were linked by intermediate junctions and desmosomes. No secretory granules were noted. The histologic, immunohistochemical, and fine structural features of these tumors were unlike those of pituitary adenoma or any other primary sellar tumor. A derivation from adenohypophyseal folliculostellate cells is suggested.

Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature.

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.

Ultrastructural observations on mitochondria and microvesicles in renal oncocytoma, chromophobe renal cell carcinoma, and eosinophilic variant of conventional (clear cell) renal cell carcinoma.

On light microscopic examination, the morphologically overlapping features of granular eosinophilic cytoplasm in renal oncocytoma and the eosinophilic variants of chromophobe renal cell carcinoma and conventional (clear cell) renal cell carcinoma may pose difficulties in diagnosis. We investigated the ultrastructure of 5 renal oncocytomas, 7 eosinophilic variants of chromophobe renal cell carcinoma, and 5 eosinophilic variants of conventional (clear cell) renal cell carcinoma. Special attention was paid to mitochondria and microvesicles and interrelations thereof. The electron microscopic features were correlated with the light microscopic findings. All of the tumors had abundant mitochondria. Although abundant microvesicles were present in all of the chromophobe renal cell carcinomas, scant numbers of microvesicles were also sometimes present in renal oncocytomas (2 of 5) and in the eosinophilic variant of conventional (clear cell) renal cell carcinoma (1 of 5). The mitochondria in all three types of renal neoplasms studied differed in morphology, being predominantly uniform and round with predominantly lamellar cristae in renal oncocytoma, variable in shape and size with predominantly tubulocystic cristae in chromophobe renal cell carcinoma, and swollen and pleomorphic with rarefied matrix and attenuated cristae in the eosinophilic variant of conventional (clear cell) renal cell carcinoma. Variable numbers of mitochondria in all of the chromophobe renal cell carcinomas had outpouchings of the outer membranes, some of which carried parts of inner membrane within them. These outpouchings closely resembled the nearby cytoplasmic microvesicles, as did the tubulocystic cristae of the mitochondria. Some microvesicles contained homogeneous, electron-dense, finely granular matrix, similar to that seen in mitochondria. In one of seven chromophobe renal cell carcinomas, microvesicles were present in rough endoplasmic reticulum, and in two others, mitochondria were present within some vesicles. These features strongly suggest a close relationship between the microvesicles and mitochondria. Based on the role of vesicle formation in normal mitochondriogenesis, and some of our observations, we propose that defective mitochondriogenesis may be the source of microvesicles in chromophobe renal cell carcinomas.

Oncocytic carcinoma (malignant oncocytoma) of the breast.

Three cases of oncocytic carcinoma of the breast observed in two women and one man are reported. One tumor was in situ and two were invasive. All three tumors were composed mostly of cells with "low-grade" nuclei and abundant granular eosinophilic cytoplasm. More than 70% of the neoplastic population in each case was immunoreactive with an antimitochondrion antibody. The presence of numerous mitochondria also was demonstrated at the ultrastructural level. Apocrine cells and oncocytes share similar morphologic features at the hematoxylin-eosin level; however, there are some differences that allow a confident distinction between these two cell types. Mitochondria in apocrine cells usually are in a perinuclear location and are not so numerous and diffusely dispersed as in oncocytes. In addition, apocrine cells display features of active secretory elements: prominent microvilli, well-developed Golgi complex, and electron dense secretory granules polarized toward the luminal pole; all these features were lacking in the three cases described. The cells constituting the present cases were not positive at the immunohistochemical and molecular levels for GCDFP-15/PIP mRNA, which are typical markers of apocrine differentiation. We suspect that mammary oncocytoma is a more common tumor than the meager number of reported cases suggests.

Oncocytic meningioma.

Six cases of meningioma showing oncocytic changes are described. The lesions were composed mostly of sheets, nests, and cords of large polygonal cells with finely granular eosinophilic cytoplasm rich in mitochondria. Neoplastic cells showed nuclear pleomorphism with prominent nucleoli. Necrosis and high mitotic rate were present in the majority of cases. Oncocytic differentiation was demonstrated by conventional histology, immunocytochemistry, electron microscopy, and Western-blot analysis. Oncocytic meningiomas showed an aggressive behavior; recurrences were observed in three cases, and invasion of brain cortex was evident in other two cases.

Soft tissue oncocytoma.

We describe a case of a novel soft tissue neoplasm, composed of a monotonous population of cells. Their cytoplasm was parked with mitochondria, and had no immunohistochemical or ultrastructural evidence of differentiation. The neoplasm, located within the thigh of a 50-year old man, was well-circumscribed but unencapsulated. The patient was clinically free of neoplasm at 1 year follow-up, after complete local excision. We propose the term "soft tissue oncocytoma" for this lesion, because of the similarity of this neoplasm to oncocytomas of other reported sites.

Renal epithelial neoplasms: the diagnostic implications of electron microscopic study in 55 cases.

Several unsettled histogenetic, nosologic and diagnostic considerations for renal epithelial tumors may have ultrastructural ramifications. Yet, a comprehensive electron microscopic study of renal epithelial neoplasms, in light of the recent classification, is not available. The ultrastructural findings from fifty-five renal epithelial neoplasms [31 clear cell renal cell carcinomas (RCC), 11 papillary RCC, 5 chromophobe RCC, 3 sarcomatoid RCC and 5 oncocytomas] were correlated with their light microscopic appearance. Clear cell RCC showed long microvilli similar to the brush border of the normal proximal tubules, with abundant cytoplasmic lipid and glycogen. Papillary RCC showed variably sized microvilli, and small amounts of cytoplasmic lipid, but no glycogen. Chromophobe RCC showed many cytoplasmic vesicles and abnormal mitochondria, with rare short and stubby microvilli. Renal oncocytoma showed many mitochondria with a few vesicles in the apical portion of the cytoplasm and rare short and stubby microvilli. The eosinophilic cell variants of clear cell RCC, papillary RCC and chromophobe RCC showed ultrastructural features similar to those of their respective prototypes, except for an increased numbers of mitochondria in the cytoplasm. One sarcomatoid clear cell RCC showed skeletal muscle differentiation. Two types of cytoplasmic inclusions, i.e. hyaline globules and granules similar to those in the Paneth cells (PC-like granules) were identified only in clear cell RCC, which displayed distinctive ultrastructural features. The current EM study demonstrates distinctive ultrastructural features of renal epithelial neoplasms. The findings lend additional support to the current classification of the pertinent tumor types, facilitate the differential diagnoses, and provide insights into the possible histogenesis of renal epithelial neoplasms.

Hyaline globules in renal cell carcinomas and oncocytomas.

Hyaline globules (extracellular collections of amorphous material) are identified in 10 of 59 renal cell carcinomas (RCC) and in 2 of 9 oncocytomas. Immunohistochemical characterization of these PAS-positive structures revealed the presence of basement membrane material in most cases. Collagen type IV and laminin were the predominant constituents, whereas fibronectin was detected only occasionally. Electron microscopic examination of the globules showed concentric multilayered accumulations of basement membrane material. No such structures were recognized in 8 renal pelvic transitional cell carcinomas nor in 2 metanephric adenomas. RCC associated hyaline globules were always negative for alpha1-antitrypsin (AAT), alpha-fetoprotein (AFP), amyloid A, cytokeratin, vimentin, or lysozyme. These features differ from those of the hyaline globules previously described in other malignant neoplasms, notably AAT-positive hyaline globules in ovarian tumors, and AFP-positive globules in yolk sac tumors. Identification and immunohistochemical characterization of hyaline globules in metastases may be helpful in determining the origin of occult primary tumors.

Renal oncocytoma and chromophobe renal cell carcinoma. A comparison of colloidal iron staining and electron microscopy.

Chromophobe renal cell carcinoma (RCC) is characterized by diffuse cytoplasmic staining with Hale colloidal iron (HCI) and the presence of numerous microvesicles. The eosinophilic variant morphologically may resemble renal oncocytoma. The latter commonly shows focal cytoplasmic HCI reactivity, but microvesicles have not been previously reported. We examined 19 chromophobe RCCs and 28 oncocytomas for their HCI staining patterns. Electron microscopy was performed on 13 chromophobe RCCs and 10 oncocytomas. In all cases of chromophobe RCC, more than 75% of cells showed a diffuse cytoplasmic HCI positivity, whereas a variable proportion of cells in 20 oncocytomas showed focal cytoplasmic staining, in a perimembranous, apical, or perinuclear pattern. Ultrastructurally, chromophobe RCCs contained abundant microvesicles with varying numbers of mitochondria, whereas all oncocytomas contained abundant mitochondria with focal collections of microvesicles. The microvesicles, in perimembranous, apical, or perinuclear clusters or singly scattered throughout the cytoplasm, were morphologically indistinguishable from those in chromophobe RCCs. In most cases, the microvesicle location and HCI staining pattern correlated. Chromophobe RCC and oncocytoma have distinctive morphologic features that usually allow their recognition. In difficult cases, HCI staining and electron microscopy may help, but the presence of HCI positivity or microvesicles in an eosinophilic renal tumor does not rule out oncocytoma.