Immunohistochemical localization of autophagosomal membrane-associated protein LC3 in granular cell tumor and schwannoma

Granular cell tumor (GCT) is a neoplasm derived from Schwann cell or (in cases arising in the neurohypophysis) pituicyte and is characterized by abundant cytoplasm filled with numerous eosinophilic granules, which have been considered autophagolysosomes on the basis of their ultrastructure. To confirm that the formation of these granules is related to an autophagy phenomenon, 12 cases of GCT (including two cases of GCT of the neurohypophysis) were studied immunohistochemically using an antibody against LC3 (microtubule-associated protein 1 light chain 3, a specific marker of autophagy). All cases of GCT showed granular immunoreactivity for LC3 in the cytoplasm of tumor cells, indicating that the formation of intracytoplasmic granules in GCT is closely related to an autophagy phenomenon. For elucidation of the relationship between GCT and schwannoma, 20 cases of schwannoma were similarly studied using the anti-LC3 antibody. In eight of 20 cases, a small number of tumor cells showed granular immunoreactivity for LC3, suggesting an increased autophagic activity in some schwannomas and further reinforcing the close relationship between GCT and schwannoma.     

Granular cell tumor arising metachronously in the bronchus and esophagus

We present a case of granular cell tumor (GCT) occurring in the esophagus 7 years after operation for bronchial GCT. A 59-year-old Japanese man complained of epigastralgia, and endoscopic examination of the upper digestive tract disclosed a submucosal tumor in the lower esophagus. Histological examination of the endoscopic mucosal resection of the esophageal tumor showed a proliferation of neoplastic cells with an eosinophilic and granular cytoplasm. The cytoplasm of the neoplastic cells was histochemically positive for PAS stain and immunohistochemically positive for S-100. This tumor did not fulfill any of the diagnostic criteria for malignancy at either the macroscopic or microscopic level. I believe that this is the first case of GCT occurring metachronously in the respiratory and digestive tracts. Clinicians and pathologists should bear in mind that GCT may arise metachronously in the respiratory and digestive tracts.     

Granular cell tumor of the neurohypophysis: report of a case with intraoperative cytologic diagnosis

Cytological techniques including touch and smear preparations are very useful diagnostic modality in the evaluation of central nervous system (CNS) lesions and, in many instances, may be effectively used as the sole modality of tissue preparation for intraoperative consultation. Cytologic preparations offer many advantages over frozen sections for CNS specimens. These include selective examination of multiple areas from small biopsy specimens, superior preservation and details of cellular morphology, fewer artifacts, faster results, and improved cost-effectiveness. We describe the cytologic diagnosis of a granular cell tumor (GCT) of the neurohypophysis in a 33-year-old male who presented with headache and blurred vision. CT scan revealed an enlarged sella with a 2.15 x 2.0 cm pituitary lesion. Transsphenoidal resection of the mass was performed and submitted for intraoperative consultation. Smears and touch preparations were made on a portion of the mass that showed uniform polygonal cells with round to ovoid nuclei and abundant eosinophilic granular cytoplasm. An intraoperative cytological diagnosis of "favor GCT" was rendered. The histologic sections of the remaining material confirmed the diagnosis. Although GCT of the neurohypophysis is very rare, a specific intraoperative cytological diagnosis is possible. We report the clinical, cytological, and pathological findings of a GCT affecting the neurohypophysis.     

The Cytology of a Thyroid Granular Cell Tumor

Granular cell tumor (GCT) of the thyroid is rare. Before this report, only four cases of thyroid GCT have been reported, none of which presented a cytopathological examination. In this paper, we report the fine needle aspiration cytology and pathological analysis of a thyroid GCT from a 12-year-old girl who presented with a painless neck mass. The tumor cells were single, in syncytial clusters, or pseudofollicles, contained small round, oval, or spindle nuclei, indistinct nucleoli, and a large amount of grayish, granular fragile cytoplasm. The background contained granular debris and naked nuclei. A differential diagnosis of thyroid GCT with more frequent thyroid lesions containing cytoplasmic granules, including Hurthle cells, macrophages, follicular cells, and cells of black thyroid syndrome, was also performed.     

Granular-cell tumor of the esophagus: Report of a case with a cytologic diagnosis based on esophageal brushing

We report a case of granular-cell tumor (GCT) in the esophagus. This is a rare location for this tumor and only 80 cases have been described. The tumor was diagnosed in a 24-yr-old woman with epigastralgia. Endoscopic examination revealed a submucosal ulcerated lesion. The smears derived from esophageal brushings contained clusters of granular cells. Histologic examination of the endoscopic biopsy provided diagnostic confirmation of GCT. To our knowledge, this is the first reported case of esophageal GCT in which the characteristic tumor cells were seen in the endoscopic brushing material. This case demonstrates that a cytologic diagnosis of GCT is possible if the lesion is ulcerated and/or brushing is subsequent to taking the biopsy. Although rare in the esophagus, GCT should be considered in the differential diagnosis of esophageal neoplasms. Diagn. Cytopathol. 1998;19:455–457. © 1998 Wiley-Liss, Inc.     

颗粒细胞瘤15例临床病理分析

目的探讨颗粒细胞瘤的组织起源及临床病理学特征。方法回顾分析15例颗粒细胞瘤的临床资料及组织学形态特征,并采用免疫组化(SP法)观察其免疫表型。结果良性颗粒细胞瘤13例,恶性颗粒细胞瘤2例。男性5例,女性10例,年龄19~69岁,平均年龄41·6岁,2例恶性颗粒细胞瘤年龄分别为67岁和69岁。良性颗粒细胞瘤直径0·4~5·3cm,平均2·3cm,2例恶性颗粒细胞瘤直径分别为6和14cm。均为单发病例,临床上主要表现为真皮、皮下或黏膜下孤立性无痛性结节,分别位于腰部3例、腋下、胸壁各2例,乳腺、上臂、子宫、肛周、声带、食管、结肠、舌部各1例。病理组织学上,良性颗粒细胞瘤的肿瘤细胞通常有比较丰富的嗜酸性颗粒状胞质和小而深染的胞核,而恶性颗粒细胞瘤的肿瘤细胞中可见带有明显核仁的空泡状核,细胞核明显异型及部分细胞呈梭形。免疫组化示神经标记物NSE、S-100蛋白强阳性,表达溶菌酶的标记物CD68也强阳性,而表达平滑肌和横纹肌的标记物SMA、MG均阴性。结论颗粒细胞瘤为来源于雪旺细胞的肿瘤,恶性者少见,大多发生在年龄大的患者,且肿瘤体积比较大。     

Granular cell tumor of the neurohypophysis: report of a case with unusual age presentation

Granular cell tumor (GCT) usually occurs as a solitary, small, nodular tumor and rarely grows to a sufficient size to present symptoms. The tumor is more prevalent in female adults. The authors report a case of an 8-year-old boy with GCT of the neurohypophysis presenting with central precocious puberty. Few cases of symptomatic GCT have been reported in the literature, none of them in a patient in the first decade of life. Clinical picture, histopathological features, and histogenesis of GCT of neurohypophysis are discussed.     

Expression of irnmunoreactivities to 75 kDa nerve growth factor receptor, trk gene product and phosphotyrosine in granular cell tumors

Nineteen granular cell tumors (GCT) of adults, two congenital granular cell epulides and five epulides fibrosae were immunohistochmically examined to detect the expression of 75 kDs nerve growth factor receptor (NGFR), frk gene product, phasphotyrosine (PT), protein gene product 9.5 (PGP9.5) and S-100 protein. The NGFR-immunoreactivity (IR) and trk gene product-IR were expressed on almost all granular cells of GCT. PT-IR was also demonstrated on granular calls of all GCT examined, although the frequency of positive cells was low. Congenital granular celi epulides and epulldes fibrosae were negative for NGFR-IR, trk gene product-IR and PT-IR. S-100 protein was localized in granular cells of adult GCT but not in the granular cells of congenital epulis. On the other hand, PGP9.5 was detected in granular cells of both conditions and in fibroblastic cells of epulis fibrosa. The present results further indicate that GCT is of peripheral nerve Schwann cell origin, while the congenital granular cell epulides are not of neural origin. NGFR and trk gene product expressed on GCT seems to be functional in terms of phosphorylation of the tyrosine residue in the receptor or downstream protein in signal transduction.     

Rhabdomyoma of the head and neck: morphology and differential diagnosis

Rhabdomyomas of the head and neck are exceptionally rare benign mesenchymal tumors. Although histology is very characteristic, several differential diagnoses have to be considered. We investigated five patients with extracardiac rhabdomyoma of the head and neck (median age 65.9 years), four of them presenting with adult rhabdomyoma (AR) and one with fetal rhabdomyoma (FR). We analyzed the histological findings, with special regard to separation from hibernoma (two patients) and granular cell tumor (GCT; six patients, median age 31 years). Both FR and AR showed polygonal eosinophilic cells with peripherally or centrally localized nuclei and cross striations, while in hibernoma, multivacuolated cells with centrally localized nuclei were detected. In GCT, polygonal eosinophilic cells with granular periodic-acid-Schiff-positive cytoplasm were found; in one case, atypical GCT with increased pleomorphism and mitotic rate was observed. Pseudoepitheliomatous hyperplasia occurred both in FR and GCT. Immunohistochemically, rhabdomyomas were strongly positive for myogenic markers (desmin, actin, and myoglobin) but negative for S-100, while hibernoma and GCT strongly expressed S-100. Concerning the differential diagnosis of rhabdomyoma, GCT has to be especially considered since this tumor can undergo malignant transformation.     

Fine-needle aspirates of granular cell lesions of the breast: Report of three cases,with emphasis on differential diagnosis and utility of immunostaining for CD68 (KP1)

Fine-needle aspiration biopsy (FNA) has been recognized as a safe and reliable procedure for evaluating breast lesions. We herein report cytologic findings for needle aspirates from three granular cell nodules of the breast. The nodules were detected by diagnostic imaging and ranged from 0.6 to 1 cm in diameter. Ultrasound-guided FNA was used in all cases and revealed cellular aspirates with similar cytomorphologic features consisting of sheets of large granular cells intersected by arborizing thin-walled blood vessels. The cells had round to oval nuclei, inconspicuous nucleoli, and abundant, often ill-defined granular cytoplasm. Tissue sections of resected specimens yielded final diagnoses of granular cell metaplasia of histiocytes and stromal cells in one case and granular cell tumor (GCT) in the other two cases. FNA smears in all three cases were strongly positive for the lysosomal marker CD68 (KP1) and S-100 protein; therefore, it was not possible to distinguish true GCT from granular cell metaplasia/granular histiocytes. When breast aspirates reveal granular cell changes, excisional biopsy should be done for a definitive diagnosis. Diagn Cytopathol 1996;15:403–408. © 1996 Wiley-Liss, Inc.     

Importance of Annulate Bodies in the Diagnosis of Granular Cell Tumors (Schwannomas)

Granular cell tumors (GCTs) were originally characterized ultrastructurally by the presence of many large lysosomes and angulate bodies (ABs). ABs appear to have been forgotten, and the diagnosis of GCT currently depends solely upon the presence of large lysosomes. Most investigators favor a Schwann cell origin for GCT. Recently, reports of granular tumors with large lysosomes but without ABs have suggested other cells of origin. If the ultrastructural criteria for the diagnosis of GCT were maintained as originally described, many of these granular tumors would not qualify as true GCTs. Two granular tumors that were at first considered GCTs are described. Based on the presence of large lysosomes and the presence or absence of ABs, one tumor was considered a true malignant GCT and the other a benign fibroblastic tumor.     

Hilar pulmonary granular cell tumor: a case report and review of the literature

We present a case of pulmonary granular cell tumor (GCT). A 35-year-old man underwent pulmonary resection for metastatic testicular mixed germ cell tumor when two interlobar lymph nodes were found to be enlarged and abnormal. Intraoperative frozen section examination showed their involvement by GCT. Histologic examination of the lobectomy specimen showed a benign, predominantly hilar GCT as well as metastatic germ cell tumor. This location, with no endobronchial component and with extension into regional hilar lymph nodes, is unusual. The differential diagnosis and the association with the metastatic testicular cancer are discussed and the literature on pulmonary GCT is reviewed.     

Granular cell tumor--a rare, benign respiratory tract neoplasm in the material of the Institute of Tuberculosis and Lung Diseases

The granular cell tumor (GCT) is a nodule that arises most commonly in the skin, the breast or the tongue. The vast majority are benign. Approximately 6-10% of granular cell tumors have been reported in the lower respiratory tract. The clinical, pathological and immunohistochemical findings of eleven cases are described in our material consisted of 6 males and 5 females aged from 35 to 58 years (median, 46 years). The GCT were solitary lesions in all our patients. The tumors were located in trachea (6 cases) and in bronchus (5 cases). They were found during bronchoscopy performed because of symptoms of pneumonia, lung cancer and hemoptysis or dyspnea alone. Diameter of the tumors ranged from 0.2-2.5 cm (median 1.2 cm). Six tumors were surgically excised and 5 were endoscopically removed. Pulmonary GCT behave in a benign fashion. It was observed that tumors of less than 8 mm were more amenable to endoscopic removal and larger tumors were more likely to infiltrate through the bronchial wall. Histologically, the GCT showed submucosal infiltrates of round or oval cells with abundant granular cytoplasm. The tumors cells were positive for S-100 protein, neuron specific enolase, CD68 and vimentin. Our immunohistochemical results are consistent with this concept.     

Granular cell tumors of the abdominal wall

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.     

Morphological study of granular convoluted tubules in the submandibular gland of the mouse during the growth of a sarcoma-180 subcutaneous tumor

Histological and cytological changes in the submandibular glands of adult male mice arising during the growth of sarcoma-180 subcutaneous tumors were studied. The submandibular glands of the mice were examined by morphometric analysis at 1, 3, 6, 10, 20, 30 and 64 days after inoculation of the tumor cells. There was a slow increase in the relative cross-sectional area of the granular convoluted tubule (GCT) in the section of the submandibular gland of the animals as the tumors grew. The increased proportional area of the GCT was significantly different from that of the control's from day 30. However, the mean weight of the glands was not increased. The proportional area of the granular cluster in the cells of the GCT of tumor cells in inoculated animals decreased about 5% on the first day and then quickly increased by 16% on the third day in comparison with those of the controls, eventually reaching a maximum of 74% (control, 54%) by day 30. In addition, the average number of granules per GCT cell decreased in the first three days, then increased to normal levels from day 6, going above the normal level from day 20 of the tumor growth. These changes in the glands of tumor-bearing animals disappeared within 20 days after removal of the tumor. These results indicate that the growth of the sarcoma-180 subcutaneous tumor caused morphological changes in the GCT and GCT cells, suggesting an alternation in the requirements of the secretions contained in the granules, such as the epidermal growth factor, during the growth of the tumor.     

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.     

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.     

Hepatocellular carcinoma with osteoclast-like giant cells: possibility of osteoclastogenesis by hepatocyte-derived cells

Giant cell tumor (GCT) of bone is a primary osteolytic tumor that is characterized by the formation of osteoclast-like giant cells. In addition to GCT of bone, extraskeletal GCT are known to be formed in several soft tissues. Giant cells in GCT of bone were suggested to be identical to osteoclasts, but the characterization of giant cells in extraskeletal GCT remains incomplete. In this study, a case of sarcomatoid hepatocellular carcinoma with osteoclast-like giant cells was analyzed. Immunohistochemistry revealed the expression of almost all markers of osteoclasts: tartrate-resistant acid phosphatase, CD68, CD51, CD54 and matrix metalloprotease-9, in osteoclast-like giant cells in the tumor. In situ hybridization revealed the expression of receptor activator of nuclear factor-kappa B (RANK) in the giant cells and receptor activator of nuclear factor-kappa B ligand (RANKL) in the tumor cells. The hepatic origin of the sarcomatoid hepatocellular carcinoma cells was confirmed by the expression of albumin. This is the first report suggesting that hepatocyte-derived cells possess the potential for osteoclastogenesis. In addition, these findings suggest that osteoclast-like cells in the hepatocellular carcinoma were formed by the same mechanism as osteoclastogenesis in bone.