Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

BACKGROUND: Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. METHODS: The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs or GCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. RESULTS: SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55 years, 44% were females, and median maximal tumor diameter at presentation was 2.1 cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9 cm vs. 2.2 cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). CONCLUSION: SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

Unique Case of Rare Non-Neural Granular Cell Tumor of the Rectus Abdominis Muscle.

Background and Objectives: Our report contributes a unique case of a non-neural GCT occurring in an unusual location, with its development during pregnancy adding to its rarity. Materials and Methods: Granular cell tumors (GCTs), also known as Abrikossoff's tumors, are rare neoplasms of Schwann cell origin with predominantly benign behavior. We present a case of a 29-year-old female with a non-neural variant of a GCT discovered incidentally during a cesarean section, situated on the posterior surface of the rectus abdominis muscle. Results: Histologically, the tumor exhibited features consistent with a benign non-neural GCT, confirmed through an immunohistochemical analysis. Despite the atypical presentation and challenging surgical removal due to prior scarring, the patient experienced no postoperative complications and showed no signs of recurrence during follow-up. Conclusions: This case highlights the importance of considering GCTs in differential diagnoses, particularly in unusual anatomical locations, and underscores the favorable prognosis associated with timely surgical intervention.

A rare case of cutaneous granular cell tumor with unusual Melan-A expression in a child.

Granular cell tumors (GCTs) are rare, indolent neoplasms classically characterized by eosinophilic granular cytoplasm, infiltrations of polygonal cells in the collagenous stroma, and pustulo-ovoid bodies of Milian. We describe a case of a 10-year-old female presenting with a GCT of the upper arm, remarkable for positive Melan-A expression without additional melanocytic features. The differentiation between granular cells versus melanocytic neoplasms carries significant implications for clinical management, and such diagnoses should be considered carefully in the setting of unusual immunophenotypes.

Primary Intraosseous Granular Cell Tumor of the Sphenoid and Central Skull Base in a Pediatric Patient.

BACKGROUND: Granular cell tumors occur in all ages and many anatomic sites. In the craniofacial region, they typically arise in soft tissue, not bone. We present a primary intra-osseous granular cell tumor of the sphenoid and central skull base arising in a 12- year- old girl. CASE REPORT: A 12-year-old female with sickle cell disease and Jeavons syndrome presented with seizures. Imaging and partial resection revealed an expansile benign granular cell tumor (GCT) involving the sphenoid body, pterygoid process, and central skull base. The disease has remained stable after 36-month follow up. DISCUSSION: GCT primarily involving the osseous sphenoid/skull base has not been previously reported in a child. Although mostly benign, some are aggressive, with malignant transformation in 1-2%. Surgery is the mainstay of treatment, but in the skull base this may be limited by adjacent critical structures. Decision-making is guided by anatomic extent, histology, and clinical behavior.

Gastrointestinal Tract Granular Cell Tumor in the Pediatric Population: A Multicenter Experience.

BACKGROUND: Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. METHODS: Multicenter retrospective study of pediatric GIT GCT. RESULTS: A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. CONCLUSION: We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.

Granular Cell Tumors of the Larynx: A Systematic Review.

OBJECTIVE: Granular cell tumor of the larynx is an uncommon, typically benign lesion that may be confused for a malignant neoplasm based on histopathology. This review examines cases of granular cell tumor of the larynx in adults to highlight key distinctions in diagnosis/management and demonstrate how misclassification may lead to unnecessary escalations in therapy. DATA SOURCES AND METHODS: A systematic search of PubMed, Ovid, and EBSCO Search Hosts was completed in December 2021. The search yielded 501 articles with 87 full-text articles included in the review. Primary search terms included granular cell, tumor, larynx, and adult. Primary endpoints were patient presentation, primary management, pathological features, and disease course. RESULTS: A systematic review of 87 articles identified 200 patients with granular cell tumors (GCTs) of the larynx. Of the 200 patients, 50.3% were males and 49.7% were females. Of these, 54.0% were reported as white patients, and 46.0% were reported as black patients. The most common presenting symptoms were dysphonia (85.9%) and stridor/dyspnea (14.1%). On examination, the lesions were most commonly polypoid/nodular and firm. Pseudoepitheliomatous hyperplasia (PEH) was identified in 33.5% of cases, and 2% of cases were malignant. GCTs were misdiagnosed as other malignant lesions in 11% of cases. In benign cases, 13.5% of patients underwent additional surgeries beyond simple excision/laryngofissure, including laryngectomy and neck dissection. Less than 2% of lesions reoccurred. CONCLUSION: Granular cell tumors of the larynx are typically benign lesions that may be misdiagnosed with unnecessary escalation of treatment. However, most lesions resolve via primary surgical excision. Laryngoscope, 134:1523-1530, 2024.

Expression of Melan-A in cutaneous granular cell tumours: a diagnostic pitfall.

Morphological overlap exists between cutaneous granular cell tumours (GCT) and malignant melanoma, with the melanocyte-specific markers HMB45 and Melan-A commonly used to support the diagnosis of melanoma. We recently encountered several cases of GCT in our practice showing strong expression of Melan-A. The aim of this study was to establish the prevalence of positive immunohistochemical staining for Melan-A and HMB45 in a series of unequivocal GCTs. We also aimed to assess the prevalence of staining for PRAME (PReferentially expressed Antigen in MElanoma), a marker expressed in >80% of primary melanomas as well as many non-melanocytic tumours. A total of 20 cutaneous/subcutaneous GCTs were evaluated using Melan-A, HMB45 and PRAME immunohistochemistry. Staining for Melan-A and HMB45 was scored using a semiquantitative scale from 0 (absent) to 3+ (staining present in >50% of tumour cells). PRAME expression was recorded as either positive (>75% of cell nuclei staining) or negative. Melan-A expression was observed in four GCTs (20%), with strong and diffuse (3+) staining seen in two cases (10%), both from anogenital areas. Weak patchy nuclear PRAME expression was seen in every case, interpreted to be negative. HMB45 was also negative in all cases (100%). Our study demonstrates that Melan-A expression can be strong and diffuse in a subset of otherwise unequivocal cutaneous GCTs, which may cause diagnostic confusion with malignant melanoma. HMB45 and PRAME did not stain any of the GCTs in our series.

Pediatric granular cell tumor of the larynx: A case report and literature review.

An 8-year-old child was admitted to our ENT department for a year because of a hoarse voice. An endoscopic examination displayed that a cystic, solid lesion can be seen in the right subglottis. The lesion was removed using a CO2 laser under general anesthesia. Postoperative histopathology confirmed granular cell tumor (GCT), S-100(+), vimentin (+), and SOX-10(+). GCT, also known as the Abrikossoff tumor, is a rare benign tumor that rarely occurs in the larynx, particularly in children. This case report emphasizes that considerable attention should be given to the differential diagnosis of the laryngeal granulosa cell tumor. Given the recurrence risk of GCT, long-term postoperative follow-up is necessary.

Clinicopathological and immunohistochemical analysis of maxillofacial granular cell tumor.

OBJECTIVES: To analyze the clinicopathological features of maxillofacial granular cell tumors (GCT) with the aid of immunohistochemical staining. METHODS: Seven cases of maxillofacial GCT were retrospectively collated, and the microscopic morphology of maxillofacial GCT was analyzed. The expression of S-100, neuron-specific enolase (NSE), SOX-10, CD68, actin, desmin, and Ki-67 in GCT was detected by immunohistochemical staining. The cases were observed in the follow-ups after clinical treatment. RESULTS: All seven GCT tumors lacked envelopes and were poorly defined. Microscopically, the sizes of the tumor cells were large and appeared with inconspicuous cell membranes, forming a syncytium-like appearance. The cytoplasm was filled with characteristic eosinophilic granules. The immunohistochemical results showed that six cases were NSE-positive, five cases were S-100-positive, seven cases were CD68-positive, five cases were SOX-10-positive, one case was actin-positive, and seven cases were desmin-negative. The Ki-67 index did not exceed 5% in all cases. In the follow-up sessions, none of the six cases presented a recurrence. CONCLUSIONS: Maxillofacial GCT has a characteristic histological structure. Immunohistochemical S-100, CD68, and other indicators can assist in diagnosis, and the prognosis is good after clinical resection.

Benign mesenchymal tumours of the tongue: A report of adult-type rhabdomyoma and granular cell tumour with a review of the literature.

The cytomorphological features of benign mesenchymal tumours of the tongue have rarely been reported. Herein, we present the cytomorphological features of adult-type rhabdomyoma, which occurred in the tongue of a female patient, and granular cell tumour (GCT), which occurred in the tongue of a male patient; both patients were in their mid-50s. The cytological features of the adult-type rhabdomyoma case included large polygonal to ovoid cells with abundant and granular cytoplasm with predominantly peripherally located, uniform, round to oval nuclei and small nucleoli. Cross-striation and crystalline intracytoplasmic structures were not seen. The cytological features of the GCT case included large cells with abundant granular pale cytoplasm, small round nuclei and small distinct nucleoli. The cytological differential diagnoses of these tumours overlap; thus, the cytological findings of the different entities included in their differential diagnoses are discussed.

Granular cell tumour in the ciliary body.

Granular cell tumours (GCTs) are benign tumours that rarely develop in intraocular regions. We report a rare case of intraocular GCT in the ciliary body. A woman in her 20s with a history of bone marrow transplantation for malignant lymphoma in early childhood was referred to our department for bilateral proliferative diabetic retinopathy. A yellowish-white ciliary tumour was observed in the temporal periphery of the patient's left eye during routine ophthalmological examination. As the tumour enlarged, we performed total resection combined with vitrectomy, silicone oil tamponade and cataract surgery. Histopathological examination revealed tumour cells with small, round or oval nuclei with eosinophilic cytoplasm. Positive immunohistochemical staining for S-100 and vimentin led to a diagnosis of ciliary GCT. No retinal detachment, proliferative membrane formation or tumour recurrence was observed 4 years postoperatively. Intraocular GCT should be considered a differential diagnosis of ciliary tumours.

Clinical and pathological analysis of congenital granular cell tumor.

OBJECTIVES: This study aims to explore the clinical and pathological characteristics of congenital granular cell tumors and provide some references for clinical diagnosis, differential diagnosis, and treatment. METHODS: Nine ca-ses of congenital granular cell tumors who visited the Children's Hospital of Zhejiang University School of Medicine from February 2008 to March 2022 were retrospectively analyzed. Herein, its clinical characteristics, pathological characteristics, treatment, and prognosis were summarized and analyzed. RESULTS: We found that nine patients were all female, aged 1­38 days when they saw the doctor. Three of them were attached in maxillary and the other six were attached in mandible. Meanwhile, six tumors were found during the mother's pregnancy at 28-39 weeks and three tumors were found at the baby's birth. One case was excised surgically under local anesthesia, and the other cases were excised surgically under general anesthesia. After 1 month to 12 years of follow-up, patients have no recurrence, however, two cases emerged new teeth from the tumor resection site. Histopathology of all excised lesions was congenital granular cell lesion. CONCLUSIONS: Congenital granular cell tumor is a benign tumor and the prognosis is good. Therefore, surgical resection of the tumor can be done without extensive resection, and it generally does not relapse. Thus, ultrasonography during pregnancy is an important method for the early detection of congenital granular cell epulis.

[Clinicopathological characteristics and differential diagnosis of 6 cases of congenital granular cell tumor].

To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.

Isolated Hypoglossal Nerve Palsy as an Early Symptom of a Granular Cell Tumor.

BACKGROUND: Hypoglossal nerve palsy (HNP) is rather common as a neurological disease. However, as an isolated nerve palsy it is an exceedingly rare phenomenon and points at local pathologies along the peripheral course of the nerve. In this communication we report a granular cell tumor (GCT) arising in the submandibular segment of the hypoglossal nerve. CASE-REPORT: Spontaneous isolated HNP was recognized in a female patient. First line MR-imaging identified a clivus-chordoma. However, involvement of the hypoglossal nerve was highly unlikely according to MR-findings. Finally, ultrasonographic investigation revealed a small submandibular mass which, at histological examination, turned out to be a granular cell tumor arising within the hypoglossal nerve. CONCLUSIONS: This is the report of an extremely rare GCT originating within the 12th cranial nerve. The case illustrates that isolated motoric cranial nerve palsy may result from this rare tumor entity. This report also points out the diagnostic value of a simple ultrasonographic investigation to depict pathologic lesions of the submandibular space.

Congenital granular cell epulis: a rare paediatric tumour of newborn.

Congenital granular cell epulis is a congenital growth rarely found on the gingiva of neonates. These remarkably large tumours present in an infant's mouth may impede with feeding, respiration or adequate mouth closure. Recognition of this entity and prompt treatment are essential for preventing any difficulties for the neonate. This is a case report of a 35-day-old female neonate who presented with a single exophytic lesion in the maxillary alveolar ridge. The differential diagnosis, management regimens and complications of this condition are reviewed. The lesion was excised under intravenous sedation and subjected to histopathological analysis. Based on the microscopic findings, the diagnosis of congenital granular cell epulis was confirmed. Clinicians including paediatricians, sonographers, dentists and surgical pathologists should be able to timely recognise and intervene such tumours as they may be potentially harmful to the infant.

An Unusual Nodular Tumour of the Penile Shaft with Clinicopathologic and Immunohistochemical Correlation.

Granular cell tumours are uncommon acquired benign tumours of nerve sheath origin that are usually seen in the head and neck region and upper aero-digestive tract. They usually present as solitary small sized nodules in middle age. The tumour is usually benign and composed of sheets of large sized cells with abundant granular cytoplasm containing lysosomal macro-inclusions known as pustulo-ovoid bodies of Milian (POB) that represent the heterogeneity of the lysosomes. No well-established criteria for malignancy have been described for this tumour. In this article, we have discussed a rare case of granular cell tumour of the penis with its characteristic histomorphology and immunohistochemistry and relevant differential diagnosis.

Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality.

PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.