Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of 45 cases

The aim of this study was to evaluate the morphological spectrum of chromophobe renal cell carcinoma (CRCC) and diagnostic utility of a panel of three immunohistochemical stains. All cases of CRCC reported between 2002 and 2012 in the Section of Histopathology, Aga Khan University Hospital, were retrieved. A total of 45 cases were identified. Slides were reviewed and immunohistochemical stains (CK7, CD117, and vimentin) were performed. Ages ranged from 18 to 90 years (mean, 48.5 years). Male-to-female ratio was 0.8:1. The tumor was located in the left kidney in 24 patients and the right kidney in 20 patients. The tumor size ranged from 3.5 to 22 cm (mean 10 cm). Histologically, 4 were classic, 22 were eosinophilic, 16 were mixed, and 3 were sarcomatoid type. Morphologic patterns included broad alveolar, solid, nested, tubular, tubulocystic, trabecular, papillary, and microglandular. Binucleation and perinuclear halos were seen in all cases. Nuclear grooves and pseudoinclusions were seen in 17 and 6 cases, respectively. Multinucleated cells were seen in 19 cases. Mitoses ranged from 1 to 11/10 HPFs (mean 3/10 HPFs). Hyalinized stroma was seen in 38 cases and calcification in 26 cases. Necrosis was seen in 18 cases. Palisading of smaller cells around the broad alveolar pattern was noted in 5 cases. The Furhman’s nuclear grade was I (11), II (26), III (5), and IV (3). Hale’s colloidal iron was positive in all cases. Immunohistochemical stain CK7 and CD117 were positive in 100% and 95.5% of cases respectively. Vimentin was negative in all cases, except in the sarcomatoid areas of 3 cases. In conclusion, chromophobe renal cell carcinoma has certain unique morphological features and immunohistochemical profile which help to distinguish it from conventional renal cell carcinoma and oncocytoma. We identified nuclear pseudoinclusions, microglandular pattern and palisading of smaller cells, which have not been reported earlier.     

Giant cell tumor of bone: An immunohistochemical comparative study

Forty-seven cases of giant cell tumor (GCT) of bone were reviewed pathologically to elucidate the origin of spindle-shaped stromal cells or the hlstogenesls of mononuclear histiocytic stromal cells and osteoclast-like giant cells (OCGC). To clarify the histogenesis of OCGC, eight cases of sarcoma associated with OCGC were reviewed for a comparative study. Spindle-shaped stromal cells sometimes produced minute foci of osteoid matrix. Proliferating cell nuclear antigen (PCNA) was observed In spindle-shaped stromal cells and mononuclear histlocytic stromal cells, but not in OCGC. Matrix metalloprotelnase (MMP)-9 was expressed by mononuclear histiocytic stromal cells and OCGC, and its expression was correlated with the lung metastasis rate. In both GCT and sarcomas with OCGC, mononuclear histiocytic stromal cells and OCGC expressed CD68, parathyroid hormone-like protein (PTH-LP), MMP-1 and MMP-9. Immunoreactivity of mononuclear histiocytic stromal cells and OCGC to CD68, PTH-LP, MMP-1 and MMP-9 was similar between GCT and sarcomas with OCGC. These observations may suggest that mononuclear histiocytic stromal cells and OCGC are reactively Induced with several cytokines acting in an autocrine or paracrine fashion and that these cells are closely related with the biologic aggressiveness of GCT.     

Giant cell tumor of tendon sheath. An immunohistochemical study of 28 cases

An immunohistochemical study was carried out on 28 cases of giant cell tumor of tendon sheath. Although this tumor has been considered to be of histiocytic origin on the basis of light and electron microscopic findings, there remains some debate about the histogenesis of the tumor. To clarify this point, by using the PAP method, each surgical specimen was stained for alpha 1-antitrypsin, alpha 1-antichymotrypsin, lysozyme, ferritin, neuron specific enolase, and S-100 protein. Tumor cells in fifteen out of 28 cases were positively stained for alpha 1-antitrypsin, 19 for alpha 1-antichymotrypsin, 23 for lysozyme, 22 for ferritin, 22 for neuron specific enolase, but no case for S-100 protein. These results suggest that this tumor is composed of cells with histiocytic character. In addition, from the immunohistochemical point of view, at least two types of giant cells seem to exist in this disease.     

Merkel cell tumor of the skin: an immunohistochemical study

Skin biopsy specimens from 12 elderly patients with Merkel cell tumors were investigated. Conventional light microscopy and immunohistochemical techniques were used. All of the tumors had similar morphologic features. Immunoreactivity for neuronspecific enolase, gastrin, calcitonin, and epithelial membrane-like antigen was demonstrated, and both neurofilaments and keratin filaments were observed. The immunohistochemical findings supported a Merkel cell origin for these Merkel cell tumors. The co-expression of neuroendocrine and epithelial markers in Merkel cell carcinomas is suggestive of neuroendocrine differentiation in a neoplasm of epithelial origin. Merkel cell carcinomas share many characteristics with neuroendocrine tumors of the bronchopulmonary and gastrointestinal tracts. All of these neoplasms may originate from cells of similar types that are present in several organs.     

胃肠道B细胞性淋巴瘤形态学及免疫组织化学分析

目的 探讨胃肠道B细胞淋巴瘤的分类特点及病理诊断.方法 对194例胃肠道B细胞淋巴瘤分别进行HE染色和免疫组织化学染色,临床病理学观察内容包括:患者性别、年龄、肿瘤发生部位、浸润深度、组织结构(淋巴上皮病变、反应性/残留淋巴滤泡、凝固性坏死/坏死碎片、结节状生长方式).免疫组织化学染色采用EnVision二步法,每例标记9种抗体,包括:Pan B、Pan T、bcl-6、CD10、bcl-10、cyclin D1,末端脱氧核苷酸转移酶(TdT)、MUM1、Ki-67.结果 194例胃肠道B细胞淋巴瘤的男女之比为1.4∶1;发病年龄最小为8岁,最大为85岁.诊断为弥漫性大B细胞淋巴瘤(DLBBCL)128例(66.0%),其中DLBCL伴黏膜相关淋巴组织边缘区B细胞淋巴瘤(MALT淋巴瘤)成分的有16例;MALT淋巴瘤40例(20.6%);滤泡性淋巴瘤(FL)8例(4.1%);淋巴浆细胞性淋巴瘤(LPL)5例(2.6%);套细胞淋巴瘤(MCL)3例(1.6%);B淋巴母细胞性淋巴瘤(B-LBL)1例(0.5%);不能分型9例(4.6%,其中5例为活检标本).发生于胃100例(51.5%)、小肠43例(22.2%)、回盲部26例(13.4%)、阑尾1例(0.5%)、结肠21例(10.8%)、直肠3例(1.6%).163例手术切除标本中侵犯黏膜层20例(12.3%)、浅肌层20例(12.3%)、深肌层19例(11.6%)、全层104例(63.8%).见有淋巴上皮病变、反应性/残留淋巴滤泡、凝固性坏死/坏死碎片、结节状生长改变者分别为52、29、66和30例.免疫组织化学标记,194例均表达CD20而不表达CD3,不同类型的淋巴瘤对bcl-6、CD10、bcl-10、cycin D1、TdT、MUM1、Ki-67有不同程度的表达.结论 胃肠道B细胞淋巴瘤主要分大B细胞性和小B细胞性两大类,小B细胞性淋巴瘤的分型是病理诊断的难点.对胃肠道B细胞淋巴瘤的诊断方法提出了建议路线.     

恶性颗粒细胞瘤临床病理、免疫组化和超微结构观察

目的：探讨恶性颗粒细胞瘤的病理学诊断和鉴别诊断要点及组织学起源。方法：对３例恶性颗粒细胞瘤进行临床病理、免疫组化及超微结构观察研究。结果：男性２例，女性１例，平均年龄为４９岁。部位分别为颈部１例，右大腿２例。其中２例分别于术后２年半及７年复发，并伴有区域淋巴结转移。组织学上３例与良性颗粒细胞瘤十分相似，局部区域出现梭形瘤细胞，空泡状核及明显的核仁，其中１例在肿瘤的周边部可见到瘤细胞与外周神经束支之间有直接移行关系。免疫酶标结果显示瘤细胞强阳性表达Ｓ－１００蛋白和神经特异性烯醇化酶（ＮＳＥ），１例电镜检测显示胞浆内充满膜包被复合性溶酶体。结论：对临床明显恶性而组织学上却极似良性的恶性颗粒细胞瘤，以下几点能提示恶性诊断：（１）肿瘤超过４ｃｍ；（２）核分裂象超过２个／１０ＨＰＦ；（３）核呈空泡状并有明显的核仁；（４）出现梭形瘤细胞；（５）有肿瘤性坏死。此外，免疫组化标记及超微结构观察有助于鉴别诊断及揭示组织学起源。     

Pulmonary endodermal tumor resembling fetal lung: a clinicopathologic study of five cases with immunohistochemical and ultrastructural characterization

Pulmonary endodermal tumor resembling fetal lung describes an uncommon neoplasm of the lung which also has been referred to as pulmonary blastoma and adenocarcinoma of fetal lung type. We describe five cases which fall within a narrow band on the spectrum of pulmonary neoplasms with both epithelial and mesenchymal features. These five cases all occurred as well-defined masses visible on chest radiograph in middle-aged females, and were treated by surgical excision. Histopathologically, low and high grades of malignancy are found. Well-formed racimose glands with cytoplasmic vacuolization resemble endometrioid carcinoma. Neoplastic columnar cells have abundant glycogen in the cytoplasm. Morules of cells within the glands have optically clear nuclei. Ultrastructurally, the optically clear nuclei are occupied by a filamentous substructure of chromatin. Multiple neuroendocrine hormones are present in low-grade malignancy. Nuclear pleomorphism, lymphatic invasion, multifocal necrosis, lack of mesenchyme at the pulmonary interface, and restricted neuroendocrine expression suggest high-grade malignancy. A mesenchymal stroma surrounding the glands is an intrinsic part of the neoplasm, but the stroma does not appear malignant, and did not form part of the metastasis in the single case where a metastasis occurred. Stromal cells show fibroblastic and myofibroblastic differentiation. Pulmonary endodermal tumor resembling fetal lung typically is a low-grade malignancy, with a better prognosis than the majority of lesions sometimes described as pulmonary blastoma or adenocarcinoma of fetal lung type.     

Giant cell fibroblastoma of soft tissue: a clinicopathological and immunohistochemical study

Giant cell fibroblastoma is an uncommon, benign tumour of soft tissue which was first described in 1982. Thirty-five cases have been previously published. Six new cases are reported herein, which have also been examined immunohistochemically for the expression of vimentin, desmin, myoglobin, S-100 protein, neurofilaments, Factor VIII related antigen and binding of the lectin Ulex europaeus. The previous literature has been reviewed. Giant cell fibroblastoma most often presents in early childhood as a slowly growing, infiltrative subcutaneous mass at a wide variety of sites. It shows a predilection for males and may recur locally in up to 50% of cases. The very distinctive histological features, characterized by so-called solid and angiectoid areas, are presented. The tumour cells were vimentin positive but negative for all other markers used. In particular, there was no evidence of endothelial differentiation. The histogenesis of this unusual tumour is discussed in the light of previous ultrastructural findings.     

Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases.

Nephrogenic metaplasia of the bladder and urethra has been the subject of extensive studies in recent years. However, information about ureteral involvement is still limited because of the rarity of the lesion. We described four cases of nephrogenic metaplasia of the ureter. They occurred in two men and two women whose ages ranged from 46 to 69 years. Three patients had stones, and one had multiple episodes of cystitis and chronic pyelonephritis. The lesions led to ureteral obstruction that in two patients was radiographically suspicious for carcinoma. Microscopically, three lesions were composed of tiny mucin-containing microcysts and medium-sized tubular structures lined by cuboidal cells that showed cytologic atypia characterized by enlarged vesicular nuclei and prominent nucleoli. However, there were no mitotic figures. Two lesions invaded the full thickness of the wall of the ureter and exhibited an infiltrative growth pattern highlighted by cytokeratin stains. The remaining two lesions were confined to the lamina propria. The cells of nephrogenic metaplasia were immunoreactive to cytokeratin 7 and AE1-AE3. They lacked reactivity for monoclonal and polyclonal CEA and p53. The MIB-1-labeling index was <5%. The cytologic atypia and infiltrative growth pattern of ureteral nephrogenic metaplasia should not be misinterpreted as evidence of malignancy. All four patients are alive and symptom free 8 months to 7 years after diagnosis.     

Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases.

We present the clinical, histologic, immunohistochemical, and ultrastructural findings of four cases of non-functioning oncocytic adrenocortical carcinomas. The patients' ages ranged from 39 to 71 years. There was no sex predilection. Large yellow-tan tumors (8.5 to 17.0 cm), well demarcated from the adjacent kidney, were seen with a thin rim of normal adrenal gland along one edge. One tumor invaded the inferior vena cava and extended up to the level of the right atrium, and another metastasized to bone. The other two tumors had similar morphologic features and therefore were considered carcinomas. Histologic sections of all four cases showed a diffuse proliferation of polygonal neoplastic cells with large nuclei containing prominent nucleoli and abundant granular and eosinophilic cytoplasm. Occasional mononuclear and binucleated giant cells were noted in one case. There were rare mitotic figures (less than one per 10 high power fields). All tumors were immunoreactive for cytokeratins (AE1/AE3 and CAM5.2). Inhibin was focally expressed by one tumor and its bone metastasis. Ultrastructurally, the cytoplasm of the neoplastic cells was packed with innumerable mitochondria. Cytologic atypia or mitotic rate cannot reliably predict the biologic behavior of oncocytic adrenocortical neoplasms. Large tumor size (4/4), extracapsular extension (3/4), blood vessel invasion (2/4), necrosis (4/4), and metastasis (1/4) are features of malignancy for oncocytic adrenocortical carcinomas. The treatment of these tumors is complete surgical excision.     

Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.     

Central granular cell odontogenic tumor: a histopathologic and immunohistochemical study

The central granular cell odontogenic tumor (CGCOT) is a rare lesion that usually affects the posterior region of the mandible of young adults. We present a case of CGCOT involving the mandible of a 20-year-old white woman, emphasizing the immunohistochemical characteristics using a large panel of antibodies. The lesion was removed surgically, and after 4 years of follow-up, there are no evidences of recurrences. The odontogenic epithelium (OE) showed positivity for cytokeratins (CKs) AE1/AE3, 34βE12, CK5, CK7, CK8, CK14, CK19, E-cadherin, β-catenin, CD138, and p63. The granular cells were positive for vimentin, CD68, lysozyme, muscle-specific actin, α-smooth muscle actin, calponin, neuron-specific enolase (NSE), CD138, and bcl-2. Dendritic-like cells surrounding the OE displayed positivity for vimentin, CD1a, S100, CD68, and bcl-2, but it was negative for factor XIIIa, supporting a Langerhans cell phenotype. Ki-67 labeling index was 1.8%, whereas p53 was negative. These data confirm the benign nature of CGCOT, the association of OE with Langerhans cells, and a variable phenotype of the granular cells.     

肾球旁细胞瘤五例临床病理分析

目的 研究肾球旁细胞瘤(JGCT)的病理形态学特点和免疫组织化学表型,提出诊断要点并探讨其组织发生。方法 采用光镜、电镜观察和免疫组织化学(链霉素抗生物素蛋白-过氧化物酶法)结合临床资料对5例肾球旁细胞瘤进行临床病理学分析,同时与血管外皮瘤、皮肤血管球瘤各5例的免疫组织化学结果进行对照。结果 JGCT女性4例,男性1例,平均年龄32．2岁,均有高血压症状。4例行肿瘤切除术,1例行肾根治术,随访4～66个月(平均27个月),5例均无复发和转移。肿瘤位于肾实质,界清,平均大小4．4cm,组织学上有以下特点：(1)瘤组织实性片状分布,细胞圆形、小多边形,大小较一致,胞质淡伊红,部分细胞含PAS阳性的嗜酸性颗粒;(2)核分裂象罕见或无;(3)间质富含薄壁血管,少量玻璃样变小血管,形成血管外皮瘤样结构,散在肥大细胞分布。电镜下找到特征性的菱形分泌颗粒。免疫组织化学结果为．JGCT瘤细胞强阳性表达肾素、CD34、肌动蛋白和calponin,而血管球瘤肾素表达阴性,血管外皮瘤肌动蛋白表达阴性。结论 IGCT是一种好发于青壮年的良性肾肿瘤,起源于演化了的动脉平滑肌细胞。确诊IGCT的关键是证实肾素分泌颗粒,对肾占位伴有高血压的患者,免疫组织化学CD34、肌动蛋白和calponin阳性在诊断中也具重要意义。     

Primary large cell neuroendocrine carcinoma of the kidney: morphologic and immunohistochemical features of two cases

Primary neuroendocrine carcinomas of the kidney are infrequent. The large cell neuroendocrine carcinoma is a subtype with an aggressive course and a worse prognosis. We report two cases, a 35-year-old man and a 75-year-old woman who died within 6 and 5-months after surgery despite radical nephrectomy and chemotherapy. Histological and immunohistochemical features are presented.     

Giant cell tumor of the lung: An autopsy case report with immunohistochemical observations

Tumors resembling giant cell tumor (GCT) of bone are well known to occur in other organs and many cases have been reported to date. While GCT occurring as primary lesions in the lung are extremely rare, the authors experienced such a tumor at an autopsy of a 77 year old woman and subsequently performed histological and immunohistochemical examinations. The clinical and morphologic characteristics of this case are documented, and the literature concerning this type of tumor is reviewed. The present tumor of the lung was histologically characterized by proliferation of benign-looking osteoclast-like giant cells in association with slightly atypical mononuclear cells. The tumor cells were immunohistochemically positive for histlocytic markers but negative for epithelial markers. This case appears to be the first reported benign giant cell tumor of the lung in which histiocytic differentiation of mononuclear cells was suggested by immunohistochemistry.     

Merkel cell tumor of the skin. Ultrastructural and immunohistochemical studies

A skin tumor of a 66-year-old female was investigated morphologically and immunohistochemically. The tumor was located within the dermis and comprised of rounded cells with scanty cytoplasm, which proliferated forming a small nest or trabecular arrangement. Electron microscopic observation indicated the presence of dense-core granules within the tumor cell cytoplasm suggesting that the tumor was derived from Merkel cells. Occasionally clusters or bundles of the intermediate filaments were found in the perinuclear cytoplasm of the tumor cells. Each tumor cell was connected with desmosomes. Immunohistochemical staining with anti-keratin antiserum showed positive reaction at the perinuclear cytoplasm of the tumor cells indicating that the cluster of the microfilaments presumably contains keratin. Conversely S-100 protein was negative in the tumor cells. The results obtained strongly suggest that the tumor or Merkel cell was considered to be derived from the epidermal immature cells rather than from the neural crest.