Immunohistochemical expression of renin and GATA3 help distinguish juxtaglomerular cell tumors from renal glomus tumors.

Juxtaglomerular cell tumors and glomus tumors both arise from perivascular mesenchymal cells. Juxtaglomerular cells are specialized renin-secreting myoendocrine cells in the afferent arterioles adjacent to glomeruli, and juxtaglomerular tumors derived from these cells are therefore unique to the kidney. In contrast, glomus tumors have been described at numerous anatomic sites and may show significant morphologic and immunophenotypic overlap with juxtaglomerular tumors when occurring in the kidney. Although ultrastructural studies and immunohistochemistry for renin may distinguish these entities, these diagnostic modalities are often unavailable in routine clinical practice. Herein, we studied the clinicopathologic features of a large series of juxtaglomerular tumors (n = 15) and glomus tumors of the kidney (n = 9) to identify features helpful in their separation, including immunohistochemistry for smooth muscle actin (SMA), CD34, collagen IV, CD117, GATA3, synaptophysin, and renin. Markers such as SMA (juxtaglomerular tumors: 12/13, 92%; glomus tumors: 9/9, 100%), CD34 (juxtaglomerular tumors: 14/14, 100%; glomus tumors: 7/9, 78%), and collagen IV (juxtaglomerular tumors: 5/6, 83%; glomus tumors: 3/3, 100%) were not helpful in separating these entities. In contrast to prior reports, all juxtaglomerular tumors were CD117 negative (0/12, 0%), as were glomus tumors (0/5, 0%). Our results show that juxtaglomerular tumors have a younger age at presentation (median age: 27 years), female predilection, and frequently exhibit diffuse positivity for renin (10/10, 100%) and GATA3 (7/9, 78%), in contrast to glomus tumors (median age: 51 years; renin: 0/6, 0%; GATA3: 0/6, 0%). These findings may be helpful in distinguishing these tumors when they exhibit significant morphologic overlap.

Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm.

Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour.

[Clinicopathologic features of glomus tumor of the kidney].

Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and ß-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

ß-catenin (CTNNB1) mutation and LEF1 expression in sinonasal glomangiopericytoma (sinonasal-type hemangiopericytoma).

Sinonasal glomangiopericytoma (SN-GPC) is an uncommon mesenchymal tumor with myoid differentiation. Recently, mutations in exon 3 of the gene coding for ß-catenin (CTNNB1) and its nuclear expression were discovered in SN-GPC. ß-catenin protein is a key regulatory molecule of the canonical Wnt signaling pathway. The expression of ß-catenin target proteins is not well characterized in SN-GPC. We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear ß-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from ß-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC.

Glomangiomyoma of the Vagina: A Report of 2 Cases and Literature Review.

We report 2 cases of vaginal glomangiomyoma in a 53-year-old who presented with a painful vaginal mass, and a 56-year-old who had postmenopausal bleeding and in whom an incidental vaginal mass was identified and resected at the time of hysterectomy. Histologic examination of the resected masses showed solid, circumscribed, benign, smooth muscle-predominant tumors with interspersed small islands of epithelioid glomus cells. The glomus cells were intimately related to small-caliber blood vessels and showed no cytologic atypia or mitotic activity. The tumor cells showed diffuse expression of smooth muscle actin, CD34, and focal expression of h-caldesmon, vimentin, and estrogen receptor. No immunolabeling for calponin B or desmin was found. To our knowledge, there are only isolated reports of vaginal glomus tumors, and these are the first reported case of vaginal glomangiomyoma in the literature.

Pericytic tumors of the kidney-a clinicopathologic analysis of 17 cases.

The pericytic (perivascular myoid cell) family of tumors is a distinctive group of mesenchymal neoplasms encountered in superficial sites and only rarely seen in viscera. The pericytic family subtends a spectrum of lesions, namely, glomus tumors and variants; myopericytoma, including myofibroma; and angioleiomyoma. In light of the contemporary classification of pericytic lesions, we identified and reviewed 17 cases of renal pericytic tumors from the files of 6 referral centers. These tumors presented over an age range of 17 to 76 years (mean 46.7, median 53), with essentially equal male-female ratio. History of hypertension (available in 11 patients) was noted in 7 (64%), which persisted even after surgical resection, including in 2 younger patients (17 and 30 years). The tumors (1.7-11.0 cm) included glomus tumors (n=11); glomangiomyoma (n=1); glomus tumor with atypical features (n=1); and angioleiomyoma (n=1), as well as tumors showing features overlapping pericytic tumor subtypes (n=3). The histomorphology observed in these renal examples closely resembled that of their soft tissue counterparts, a subset with symplastic changes and atypical features, and pericytic immunophenotype. Despite large size and deep site, no progression was identified during a median of 7 months follow-up (1-62 months). In context of prior reported experience, our series identifies a wide morphologic spectrum, including lesions presenting composite morphologies. Taken with the experience of others, our series further corroborates that malignant behavior is rare, and that criteria associated with aggression among soft tissue pericytic tumors may not be predictive for those in the kidney.

Phenotypic characterization of perivascular myoid cell neoplasms, using myosin 1B, a newly identified human pericyte marker.

Our aims were to identify pericyte-specific markers for the analysis of formalin-fixed, paraffin-embedded human tissue samples, and to characterize perivascular myoid cell neoplasms phenotypically. Previously identified pericyte markers failed to distinguish pericytes from other cellular types, such as vascular smooth muscle cells (vSMCs) and fibroblasts, in immunohistochemistry analysis. However, we compared gene expression profiles between pericytes, vSMCs, and fibroblasts, and performed human skin vasculature immunohistochemistry analysis, which led to the identification of myosin 1B (MYO1B) as a novel pericyte marker. Afterward, we investigated the expression levels of MYO1B and h-caldesmon (h-CD) in perivascular myoid cell neoplasms, angioleiomyomas (n=28), glomus tumors (n=23), and myopericytomas (n=3). Angioleiomyomas were shown to contain MYO1B-negative and h-CD-positive (MYO1B-hCD+) tumor cells, with vSMC features. Glomus tumors were predominantly composed of the MYO1B+hCD+ tumor cells, with the intermediate features between pericytes and vSMCs, whereas MYO1B+hCD- tumor cells with pericytic features and/or the MYO1B-hCD+ tumor cells with vSMC features were frequently found in these tumors. The perivascular concentric pattern of 2 myopericytoma cases was composed of MYO1B+hCD+ tumor cells, whereas that of one myopericytoma contained MYO1B-hCD+ tumor cells. These results indicate that the ability to distinguish between these cell types may allow us to understand the differentiation and origin of perivascular myoid cell neoplasms. This is the first study to identify cell properties of perivascular myoid cell neoplasms by using a pericyte-specific marker with considerably lower expression in vSMCs and fibroblasts.

Malignant Glomus Tumor Arising in a Long Standing Precursor Lesion.

Malignant glomus tumor is an exceedingly rare vascular malignancy of unclear etiology, which is believed to arise de novo or from malignant transformation of a benign glomus tumor. The authors present a case of an elderly woman evaluated for a painful 2.5-cm purple-brown tumor on the right forearm that grew rapidly within a long-standing, seemingly benign lesion. An excisional biopsy revealed a multilobular dermal tumor composed of areas of benign-appearing glomus tumor cells interspersed with areas of dense, pleomorphic cells arranged in sheets and fascicles with an elevated mitotic rate. The diagnosis of malignant glomus tumor was made on the basis of the lesion's nuclear atypia and elevated mitotic rate. This case demonstrates malignant transformation of a presumably benign glomus tumor precursor lesion highlighting this rarely reported phenomenon. The authors present this case to raise awareness of this vascular malignancy that carries a significant risk of metastasis.

Malignant glomus tumor of trachea: a case report with literature review.

Glomus tumors of the trachea are extremely rare and generally benign, with very few cases of malignant transformation reported in literature. We present the case of a 74-year-old man explored for cough and dyspnea. Bronchoscopy showed a polypoid mass arising from the posterolateral tracheal wall. Computed tomography demonstrated a mid-tracheal tissular mass obliterating the tracheal lumen. Resection and anastomosis of the trachea were performed. The histological and immunohistochemical findings were consistent with malignant glomus tumor.

Symplastic Glomus Tumor.

Glomus tumors showing nuclear pleomorphism without any other malignant features have been defined as symplastic glomus tumors. This type of glomus tumor is rarely encountered. Another case of symplastic glomus tumor is described in this study. A 37-year-old woman referred to the hospital with the complaint of a palpable tender nodule on the fourth finger tip of her left hand. The lesion had been present for about a year and aggravation of tenderness upon cold exposure was conspicuous. It was a 0.5 cm well circumscribed lesion with round to cuboidal epithelioid cells showing high grade nuclear pleomorphism. Nests of cells more uniform in shape and showing punched out nucleus representative of typical glomus tumor could also be observed. Immunohistochemical study showed expression of smooth muscle actin, caldesmon and vimentin. Ki-67 labeling index was undetectable. Investment of tumor cells was shown by type IV collagen. In contrast to its atypical cellular morphology, symplastic glomus tumor clinically behaves benign, and it is important to differentiate it from malignant glomus tumor as well as other primary or metastatic malignant tumors.

[Glomus tumor of kidney: Unusual location of a rare mesenchymal tumor]. / Tumeur glomique rénale : localisation inhabituelle d'une tumeur mésenchymateuse rare.

Glomus tumors are rare mesenchymal tumors, mostly cutaneous or subcutaneous, for which visceral locations have been described. We report the case of a solid renal glomus tumor incidentally discovered in a 60-year-old patient. The tumor was 25mm wide and was mainly composed of glomus cells expressing smooth muscle actin and vimentin. These cells were negative for cytokeratin, neuroendocrine markers and renin. Glomus cells were associated with blood vessels and bundles of smooth muscle fibers. The purpose of this work is to report the diagnostic criteria, signs of malignancy and main differential diagnosis of these rare tumors whose prognosis is usually excellent after complete surgical resection.

Diagnostic utility of endoscopic ultrasound-guided fine-needle aspiration biopsy for glomus tumor of the stomach.

A 52-year-old man was referred for further investigation of a gastric submucosal tumor on the greater curvature of the antrum. Endoscopic ultrasonography demonstrated a hypoechoic solid mass, which was primarily connected to the muscular layer of the stomach. We performed endoscopic ultrasound-guided fine-needle aspiration biopsy. The pathological examination showed proliferation of oval-shaped cells with nest formation, which stained strongly positive for muscle actin, and negative for c-kit, CD34, CD56, desmin, S-100, chromogranin, and neuron-specific enolase. Therefore, we performed laparoscopy and endoscopy cooperative surgery based on the preoperative diagnosis of glomus tumor of the stomach. The final histological diagnosis confirmed the preoperative diagnosis. Although preoperative diagnosis of glomus tumor of the stomach is difficult with conventional images and endoscopic biopsy, endoscopic ultrasound-guided fine-needle aspiration biopsy is an essential tool to gain histological evidence of glomus tumor of the stomach for early diagnosis.

Glomus tumor of uncertain malignant potential of the lung: a case report and review of literature.

Glomus tumor is an uncommon tumor usually presenting in the dermis. Rarely, it occurred in visceral organs including stomach, liver and long. The majority of glomus tumors were benign. Herein, we present a case of glomus tumor located in the left lobe of the lung in a 49 year-old Chinese male. An irregular mass measuring 3 cm was detected by imaging examination because of his suffering from cough, dyspnea and chest pain. Histologically, the tumor is composed predominantly of sheets of ovoid to round cells with clear border, pale cytoplasm and fine granular chromatin. The mitotic count was less than 5 per 50 HPF. The tumor focally invaded the surrounding normal bronchial and alveolar tissue. Immunohistochemical staining showed that the cells were diffusely positive for SMA, caldesmon, and vimentin. The Ki-67 proliferation index was approximately 20%. Based on morphologic features and the immunohistochemical profile, the tumor was consistent with glomus tumor of uncertain malignant potential.

Low-grade small round cell tumor of the cauda equina with EWSR1-WT1 fusion and indolent clinical course.

We report a case of a longstanding, large tumor involving spinal nerve roots of the cauda equina. The tumor showed small round cells arranged in nests and cords and immunophenotypic features of a glomus tumor, along with infrequent mitoses and a low Ki-67 labeling index, but exhibited some rosette-like structures, with focal CD99 and Neu-N expression. Subsequent molecular analysis showed the presence of an EWSR1-WT1 gene fusion by fluorescence in situ hybridization, which was confirmed by reverse- transcriptase polymerase chain reaction. To our knowledge, this is the first case reported with EWSR1-WT1 fusion in a small round blue cell tumor with smooth muscle differentiation and an indolent course.

Extradigital Symplastic Glomus Tumor of the Hand: Report of 2 Cases and Literature Review.

Glomus tumor is a rather common tumor of the hand, which presents with a classic triad of symptoms of high temperature, sensitivity and pain, and localized tenderness. Most glomus tumors are located in the digits, especially in subungueal areas. However, extradigital tumors are less frequent, and little is known about their clinical and histopathological features. Two cases of extradigital symplastic glomus tumor are presented. An active clinical and pathological awareness to avoid misdiagnosis or delayed diagnosis of this uncommon lesion is highlighted.

Glomangioma of the nasal septum: a case report and review.

Glomangioma is a painful, blue-red tumor that appears as a solitary encapsulated nodular mass, almost always on the skin. The first case of nasal glomangioma was reported in 1965. Since then, only 31 other cases have been reported in the literature. We present a new case of glomangioma of the nasal septum in a 61-year-old woman. The tumor was removed via an intranasal endoscopic excision. No recurrence was found at 3 years of follow-up. Our challenge was to distinguish the glomangioma from a true hemangiopericytoma and a paraganglioma.

Glomangioleiomyoma of the orbit--a case report.

Soft-tissue glomus tumours are benign lesions derived from the glomus bodies, which are specialized arteriovenous shunts that serve a thermoregulatory function and are concentrated in the distal extremities of the dermis. Glomangioleiomyoma is rarely found in the orbit, most likely because of the paucity of smooth muscle and glomus bodies in this location. We report the case of a woman with exophthalmos in whom computerized tomography and magnetic resonance imaging showed a large, lobulated mass in the right intraconal space.