Immunohistochemical study of granular cell tumors and granular pituicytes of the neurohypophysis

Six neurohypophysial GCTs and 31 normal neurohypophysis were studied by immunohistochemical techniques. The latter were grouped into A (< 5 yr old), B (30–49 yr), and C (> 70 yr). GCTs were all labeled by PNA, and some showed reactivity for S-100 protein, AAT, AAC, and cathepsin B. In addition, some were oxytocin- and vasopressinpositive. Unlike extracranial GCTs, neuron-specific enolase, myelin basic protein, and vimentin were not detected. Glial fibrillary acidic protein, keratin, and desmin were also not observed. In contrast, a few cells of the normal neurohypophysis showed immunoreactivity for AAT, AAC, cathepsin B, and PNA, similar to the cells of GCT. These cells tended to increase in number with age: group A showed fewer cathepsin B-positive cells than groups B and C (p < 0.001). These results show that neurohypophysial GCTs have some features that differentiate them from extracranial GCTs, for which a Schwann cell origin has been proposed by many authors. It was concluded that neurohypophysial GCT may originate from the cells that showed similar immunoreactivity, the “granular” pituicytes. Our results also support the hypothesis that neurohypophysial GCTs are an age-related metabolic disorder of lysosomes rather than true neoplasms.Endocr Pathol 4:140–145, 1993.     

Gingival granular cell tumors of the newborn. An ultrastructural and immunohistochemical study

Gingival granular cell tumor of the newborn, or congenital epulis, is a rare congenital lesion of uncertain histogenesis located exclusively on the alveolar ridge with marked predilection for female infants. Although histologically similar to the more ubiquitous granular cell tumor or myoblastoma, ultrastructural and immunohistochemical studies support separate histogenetic pathways for the two lesions. A newborn female infant with three gingival granular cell tumors is described herein along with immunohistochemical and ultrastructural observations. There was positive immunostaining for vimentin but staining for S100 protein was uniformly negative. Immunocytochemical assay for estrogen and progesterone receptors was also negative. The findings indicate a mesenchymal origin and the demonstration of intermediate filaments with fusiform electron densities suggests that some of the granular cells have morphologic attributes of myofibroblasts.     

Various aspects of the morphology of granular cell tumors

Histology and ultrastructure of human granular cell tumors (GCT) are studied. Apart from "granular" cells which are the main component of the tumor, GCT contain the cells of ordinary structure with signs of neurogenic differentiation, cell processus typical for the nervous tissue and peripheral nervous tissue tumors (these processus are in a close space connection with "granular" cells) as well as structurally transitional cells. This implies that "granular" cells are likely to originate from the ordinary lemmocytes as a result of disturbance and hypertrophy of intracellular processus. Preoperative diagnosis of this rare peculiar neurogenic tumor is difficult and the diagnosis is possible only after the operative material examination. If other signs of malignancy are lacking, infiltrative growth typical for these tumors allows one to consider them locally-destructive neoplasms.     

Electron microscopic diagnosis of granular cell tumors]

In tumour cells organspecific ultrastructural features are retained that may be of value in differential diagnosis. For this purpose not only fresh material but also that fixed formerly in formalin may be used.     

Expression of calretinin and the alpha-subunit of inhibin in granular cell tumors

Granular cell tumors (GCTs) typically express S-100 protein, which has been used as a marker in differential diagnosis. Calretinin, a calcium-binding protein related structurally to S-100, and inhibin, a polypeptide hormone secreted primarily by ovarian granulosa cells and testicular Sertoli cells and functioning as an inhibitor for pituitary follicle-stimulating hormone secretion, are potentially useful but not well-evaluated markers for GCTs. We studied 43 cases of GCT with antibodies to calretinin, the inhibin alpha-subunit, and S-100 protein. All tumors were positive for inhibin alpha-subunit and S-100 protein, with 50% or more cells showing moderate to strong staining. Forty tumors (93%) were positive for calretinin, ranging from focal weak to diffuse strong staining. Enhanced staining for calretinin in the tumor cells adjacent to hyperplastic squamous epithelium was observed in 9 of 13 cases showing pseudoepitheliomatous hyperplasia. Calretinin and the inhibin alpha-subunit are useful markers for GCTs. The expression of calretinin, a primarily neuronal protein, in GCTs further supports its neural differentiation or derivation. The elevated calretinin expression in the tumor cells adjacent to the hyperplastic squamous epithelium suggests a role for calretinin in the tumor cells-squamous epithelium interaction.     

Colocalized granular cell tumor and infiltrating ductal carcinoma of the breast

A 57-year-old woman presented with a 2-year history of a palpable mass in the upper inner quadrant of the right breast. A 1.1-cm, poorly circumscribed, firm tumor nodule was noted, consisting of 2 histologically distinct lesions in the same location, with some areas showing purely well-differentiated invasive ductal carcinoma and others composed of granular cell tumor. In 1 area, the 2 tumors collided and infiltrated each other. The invasive ductal carcinoma was admixed with ductal carcinoma in situ of solid and cribriform types. To our knowledge, this is the first case report demonstrating colocalization of these 2 neoplasms, which raises questions regarding causal relationship. We also review the literature on granular cell tumor of the breast.     

Renal tumors exhibiting granular cytoplasm.

Renal epithelial neoplasms consist of a group of distinct genetic and clinical entities that occasionally have overlapping morphological features. Pronounced cytoplasmic granularity or eosinophilia may be seen in a number of tumor types, including conventional (clear-cell) carcinomas, papillary carcinomas, chromphobe carcinoma, collecting duct carcinomas, and oncocytomas. Mesenchymal neoplasms such as angiomyolipomas as well as metastatic lesions such as malignant melanoma may have marked epithelial features and cytoplasmic granularity, thus mimicking a renal epithelial tumor. The same can be said for adrenal cortical neoplasms, which sometimes may be confused clinically, radiographically, and pathologically with a renal neoplasm. Close attention to morphological and cytologic detail will solve the differential diagnosis in the majority of cases, although some will require ancillary studies such as histochemistry, immunohistochemistry, and election microscopy. In a small percentage of cases molecular genetic studies are required to properly classify the tumor.     

Eosinophilic granular cells in a cryptorchid testis

Intratubular cells with numerous refractile eosinophilic cytoplasmic granules were identified in a cryptorchid testis from a 17-year-old boy. The staining properties of the granules and the ultrastructural features were studied. The accumulation of lipid or lysosomal inclusions accounted for the observed cytoplasmic granules. These granular cells were probably altered Sertoli's cells, the exact nature and significance of which need further study.     

消化道颗粒细胞瘤的12例临床病理分析

目的探讨消化道颗粒细胞瘤(granular cell tumor,GCT)的临床病理特点、诊断及鉴别诊断。方法对12例消化道GCT进行临床资料分析,病理形态观察及免疫组织化学检测。结果 12例消化道GCT形态相似,肿瘤细胞多呈巢状和片状排列,瘤细胞体积大,形态单一,多边形或梭形,胞质丰富,嗜酸性颗粒状。免疫组化显示肿瘤细胞呈S-100和vimentin弥漫阳性;CD68散在阳性;而上皮细胞标记EMA、CK(AE1/AE3)呈阴性。结论消化道GCT是一种少见的神经源性肿瘤,多为偶然发现,内镜和形态学上容易误诊,免疫组化对鉴别诊断有重要意义。     

Multifocal granular cell tumors of the gastrointestinal tract: Immunohistochemical findings compared with those of solitary tumors

Granular cell tumors (GCT) are infrequently found in the gastrointestinal tract (GIT), and only four previous reports have described lesions occurring simultaneously in different sites. The present case of 11 GCT, located in the esophagus, stomach, colon and pericolic adipose tissue, occurred in a 50-year-old Japanese woman. All GCT appeared histologically benign and there was no sign of recurrence at 3 years after surgery. Immunohistochemical analysis and comparison between this case of multifocal GCT and six cases of solitary benign GCT of the GIT, which were taken from the files of the Department of Pathology at Kitasato University (1986–2000), demonstrated the follow-ing: (1) all diffusely expressed S-100, DCC and bcl-2, and (2) median labeling indices for Ki-67, cyclin D1, p53 (Pab1801), and p21^WAF1/CIP1 of 4%, 24%, 1% and 28%, respectively, for the multifocal tumors, and 3.5%, 23%, 1% and 29%, respectively, for the solitary lesions, with no significant difference between the two groups. Thus, the expression of cyclin D1 and p21^WAF1/CIP1 may be involved in the tumorigenesis of both types of GCT. The present case emphasizes the need to evaluate the entire GIT when a single GCT is identified. Multifocal lesions should be treated conservatively by local excision because, as with the solitary tumors, they exhibit a benign biological behavior, consistent with their low Ki-67 immunoreactivity.     

Leiomyoma exhibiting a marked granular change: granular cell leiomyoma versus granular cell schwannoma.

Granular change of leiomyoma or granular cell leiomyoma is rare and not well recognized. It may be confused with the common variety of granular cell tumor, which is currently regarded as being of schwannian origin. A case of granular cell leiomyoma in the periurethral region of a 40-year-old woman is reported. Microscopy indicated that the tumor consisted of polygonal or fusiform cells with coarse, granular eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for desmin and actin, but negative for neuron-specific enolase and S-100 protein. Electron microscopy revealed myofilaments in the tumor cells, thus documenting the myogenic origin of the granular cells. The granules were ultrastructurally similar to those of granular cell schwannoma as described in the literature. It is likely that granular cell tumor arises from different tissues.     

Malignant granular cell tumor.

We report a case of malignant granular cell tumor of the chest wall that recurred in the right breast with axillary lymph node metastases. The recurrent tumor clinically and grossly mimicked a breast carcinoma. Electron microscopy and immunohistochemical techniques were used to confirm the cytologic and histologic diagnosis of granular cell tumor. The importance of true metastases in the diagnosis of malignant granular cell tumor and their differential diagnosis are discussed.     

Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy.

Incidentally detected pituitary adenomas were investigated in 100 pituitary glands at autopsy to determine the number, cell type, and location of tumors, and the presence of coexisting granular cell tumors in the neurohypophysis. Pituitary glands were sagittally sectioned at 1.5-mm intervals in toto and embedded in 1 cassette to orient location of each tumor. Twenty-four pituitary glands harbored adenomas, most smaller than 3 mm and the largest 6 x 5 x 4 mm. Two pituitary glands contained double adenomas of immunocytochemically different cell types. Of the 26 adenomas, 10 had lactotrophs, 2 had mixed lactotrophs-somatotrophs, 1 had mixed lactotrophs-luteinizing hormone cells, and 12 were nonfunctioning. One adenoma with adenocorticotropic hormone cells was also detected. Thus 25 of 26 (96%) adenomas were either lactotrophic or nonfunctioning; this percentage is much higher than that of surgically resected tumors. Twenty-two tumors were contiguous with or adjacent to the capsule from which the adenomas originated. Nine granular cell tumors were noted in the neurohypophysis; 3 coexisted with pituitary adenomas. Fourteen additional cases revealed small granular cell nests. Thus the incidental finding of nonfunctioning pituitary adenomas is relatively common in adults (24% of cases in this study), and the coexistence of pituitary adenomas and granular cell tumors may suggest a possible histogenic connection between anterior and posterior pituitary tumorigenesis.     

47例软组织颗粒细胞瘤临床病理分析

目的回顾性分析47例软组织颗粒细胞瘤(GCT)的临床病理特征并行增殖活性检测。方法收集1975至2008年武汉大学附属医院病理科GCT存档资料47例,分析其临床及组织病理学特征并随访,应用免疫组化方法行S-100、CD68、NSE及Ki-67染色。结果 GCT好发于舌部,女性多见。镜下观察所有肿瘤由多边形瘤细胞组成,胞质中有丰富的嗜酸性颗粒,且S-100、CD68及NSE染色均为阳性。24例良性GCT呈膨胀性生长,其余20例良性及3例细胞不典型性病例均为侵袭性生长。少数肿瘤细胞Ki-67染色阳性。随访的30例中1例肿瘤细胞明显呈不典型性者复发并死亡,1例细胞典型性者复发后组织学呈不典型性,1例细胞典型性者复发两次后组织学呈恶性,27例无复发。结论大多数软组织GCT为良性,少数具有潜在恶性,应注意随访。少数肿瘤细胞Ki-67阳性提示该肿瘤具有较低的增殖活。     

Types of myoepithelial cell proliferation in dyshormonal breast dysplasias and benign breast tumors

Myoepithelial cells (MC) were identified and types and forms of their hyperplasia in dysplasias and bening mammary gland tumors in dog and man were studied by indirect Coons' method using highly purified monospecific antiserum to smooth muscle myosin and by performing alkaline phosphatase test. Operation material from 75 patients and 12 dogs was studied by immunohistochemical method and from 26 persons and 12 dogs by histochemical method. Comparative analysis of immunohistochemical and histochemical identification of MC revealed differences in the results of staining in 7 out of 38 observations due to negative test for alkaline phosphatase in the presence of fluorescence. A high degree of coincidence of positive tests in immunohistochemical and histochemical methods of the study suggests that the test for alkaline phosphatase is a sufficiently reliable marker of MC. The principal similarity of types and forms of MC hyperplasia in canine and human mammary gland tissue indicates that dogs may be used as an adequate model for the study of various diseases of this organ. In addition to the known centripetal and centrifugal types, a uniformly concentric and smooth-muscle proliferations of MC were distinguished in parallel immunohistochemical and histochemical studies on variants of MC proliferation.