Abundant Eosinophilic Granular Cytoplasm Research Articles

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Multiple Congenital Granular Cell Epulis Involving Different Parts of the Oral Cavity: A Case Report.

Congenital granular cell epulis (CGCE) is a rare disease, particularly when it affects multiple oral and maxillofacial regions. We present the case of a female neonate with 4 asymptomatic masses attached to the maxillary and mandibular gingiva as well as the tongue. Due to the size of the masses causing feeding and respiratory difficulties, lesion removal was performed under general anesthesia. Histopathological analysis revealed tightly arranged polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemically, the cells were negative for Smur100 (S-100), neuron-specific enolase (NSE), cluster of differentiation (CD) 68, and Sry-related HMG box (SOX)-10, and positive for alpha-1-antitrypsin (AAT) and vimentin. The diagnosis of multiple CGCEs was established through clinical examinations, histomorphometrical, and immunohistochemical analyses. In conclusion, CGCE should be considered in the differential diagnosis of intraoral lesions in neonates.

A Rare Case of Granular Cell Tumour of Tongue in a 13-year-old Girl

Granular Cell Tumour (GCT) is a rare benign tumour that usually affects adults in the third to sixth decades, with females being more commonly affected. Here, a rare case of GCT occurring in a 13-year-old child is presented. A young girl presented with a painless swelling on the right-side of her tongue. Her past medical history was unremarkable. Upon examination, a firm, well-defined, non pulsatile, non tender lesion measuring 1×0.8 cm was noted, involving the right lateral border of the tongue. The lesion was excised and sent for histopathological examination. Gross examination revealed a 1×0.8×0.6 cm mass with a grey-white cut surface. Microscopy showed hyperplastic stratified squamous epithelium overlaying a submucosal tumour composed of polygonal cells arranged in sheets. The tumour cells had central small round nuclei with abundant granular eosinophilic cytoplasm and intervening skeletal muscle fibres. No necrosis, atypia, or increased mitosis were observed. Immunohistochemistry showed strong nuclear positivity and bright granular cytoplasmic positivity for S-100, confirming the diagnosis of GCT. The patient was followed-up for 14 months after surgery and reported no recurrences. GCTs typically manifest in older individuals, with the highest prevalence in the fifth and sixth decades of life. However, this case deviates from the norm, being noted in a 13-year-old child. This exceptionally unusual presentation should prompt the inclusion of GCT in the differential diagnosis of tongue neoplasms in paediatric patients as well. Periodic follow-up of these patients is recommended to detect malignant transformations and late recurrences at early stages.

True Oncocytic Acinic Cell Carcinoma: A Case Image.

A 67-year-old female with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presented with right sided otalgia and a 2-3 cm firm, tender right posterior parotid mass. Fine needle aspiration biopsy (FNAB) established a diagnosis of acinic cell carcinoma (AciCC). Further workup demonstrated lung nodules which were confirmed by FNAB to represent metastatic AciCC. A right radical parotidectomy with sacrifice of the facial nerve, segmental mandibulectomy, and selective neck dissection (levels II-IV) was performed. Microscopically, the tumor displayed an infiltrative border with a solid multinodular growth pattern and fibrosclerotic septation. The tumor was composed mainly of uniform cells with abundant eosinophilic granular cytoplasm with round nuclei with prominent nucleoli. Nuclei were fairly monomorphic, mitotic counts were 3-4 per 2mm2 and there was no necrosis despite the aggressive growth pattern. An anti-mitochondrial immunohistochemical stain showed strong reactivity in the tumor cells, with an internal positive control of adjacent striated ducts. An immunohistochemical stain for NR4A3 demonstrated strong nuclear reactivity in the tumor cells. Electron microscopy highlighted the tumor cells with numerous mitochondria and distinctive electron dense intramitochondrial inclusions. Concurrent CLL/SLL was identified on histologic examination of the lymph nodes, but they were free of AciCC. After eight weeks of follow-up, she tolerated the surgery well and is currently receiving radiation therapy to the parotid and neck. In this illustrative case, we justify the oncocytic designation of AciCC by morphology, immunohistochemistry, and electron microscopy.

Rhabdomyoma of the Oral Cavity Mimicking Reactive Lesions: A Case Report and Review of the Literature.

Extracardiac rhabdomyoma is a tumor that rarely occurs in head and neck region. Adult and fetal types of extracardiac rhabdomyoma are diagnosed only by histopathological examination. In the oral cavity, this lesion usually affects the mouth floor and tongue. Despite the low incidence, adult rhabdomyoma should be considered in the differential diagnosis of oral cavity lesions, and histopathological evaluation might be helpful for the final diagnosis. This study aims to report a rare case of rhabdomyoma mimicking reactive lesions and review the literature. A 34-year-old male was referred to the pathology department with a yellowish sessile lesion in the labial maxillary vestibule. During an excisional biopsy, a mass of unencapsulated soft tissue beneath the vestibular mucosa was observed. The yellowish color in clinical features has led to lipoma as the initial clinical diagnosis. The histological examination exhibited an encapsulated, well-circumscribed benign neoplasm composed of multiple lobules of large polygonal cells with prominent abundant granular eosinophilic cytoplasm. No cellular atypia was observed. Diagnosis of the adult type of rhabdomyoma was made by collective agreement. Rhabdomyoma can be mistaken for other reactive lesions and may resemble their appearance.

DIFFUSE ECTOPIC DECIDUOSIS MIMICKING AS PERITONEAL CARCINOMATOSIS: A CASE REPORT OF A YOUNG FEMALE WITH MULTIPLE SEROSAL AND OMENTAL NODULES FOUND DURING A CAESARIAN SECTION

Background & Objectives: Ectopic deciduosis refers to an abnormal occurrence of decidual tissue beyond the endometrium, predominantly on the surface of the uterus, fallopian tubes, ovaries and omentum. Diffuse omental and perito-neal involvement is a perplexing manifestation that may mimic peritoneal carcinomatosis. It is not accompanied by any symptoms and complications in most of the cases and does not require treatment. However, rarely it can present with acute abdomen or imitate peritoneal malignancy and, thus, associated with diagnostic difficulties and unnecessary interventions. Aim of this case report is to describe a rare case of peritoneal deciduosis in a young female, found incidentally, during a caesarean section, mimicking metastatic nodules. Afutile hysterec-tomy along with omentectomy was performed.
 Methods: A case of diffuse ectopic deciduosis mimicking as peritoneal carcinomatosis in a 29 years young female with full term pregnancy was found during a lower segment caesarian section, undertaken in a tertiary care teaching hospital of Lahore, Pakistan. The histopathological diagnosis was based on common technique of paraffin embedding and hematoxylin-eosin staining along with ancillary immune-histochemical evaluation.
 Results: Histopathological evaluation showed ectopic decidual tissue consisted of solid nests and loosely cohesive aggregates; large polygonal cells with abundant granular eosinophilic cytoplasm; sharply defined cell borders, bland nuclei with dispersed chromatin and single conspicuous nucleoli on the surface of uterus and in omental fat. Weak staining for CD30 was observed in the decidual cell cytoplasm and negative staining for CK and Calretinin in decidual cells was found. Calretinin and CK highlight benign mesothelial cells and help to rule out differentials of mesothelioma and metastatic carcinoma.
 Conclusion: Peritoneal deciduosis represents a rare entity and it is important to consider this condition in patients, especially in pregnant women, to prevent unnecessary intervention In addition, distinguishing this condition from malignant neoplasms will help in deciding correct treatment options.

An Intriguing Case of Chronic Peristomal Ulcer.

An Intriguing Case of Chronic Peristomal Ulcer.

A pediatric case of anaplastic pleomorphic xanthoastrocytoma (Grade 3)

Pleomorphic xanthoastrocytoma (PXA) is a glial tumor which accounts for less than 1% of astrocytomas. PXA most commonly occurs in the temporal lobe in the outer cortex of brain and usually seen in young adults and children. As per 2020 WHO classification of CNS tumors, PXA with a mitotic activity ≥5 mitoses/10 HPF is defined as anaplastic pleomorphic xanthoastrocytoma (APXA), WHO grade 3. Here we present a rare case of Anaplastic Pleomorphic Xanthoastrocytoma developing in a female child of 11 years of age.A 11 years old female child presented with symptoms of continuous headache, giddiness, fever and vomiting since last 15 days. Computed Tomography of her brain revealed a soft tissue density mass lesion in right temporal lobe involving the insular cortex and capsuloganglionic region. The radiological differential diagnosis was a neoplastic lesion, most likely glioma. The patient underwent surgery for removal of temporal lobe tumor and the resected tumor bits were sent for histopathological assessment. Microscopically, many multinucleated lipidized giant cells were seen having eccentrically pushed nuclei, conspicuous nucleoli and abundant eosinophilic granular cytoplasm. A second population of few spindled cells with less amount of cytoplasm was also noted in the intervening parenchyma. Immunohistochemical workup showed the tumor to be positive for GFAP, S-100, Synaptophysin, p53 and CD-68. The tumor was negative for CD34. Ki-67 index was 15-20%. A final diagnosis of Anaplastic Pleomorphic Xanthoastrocytoma (grade 3) was made.APXA is a rare astrocytic tumor and has relatively more aggressive radiological and histomorphological features than pleomorphic xanthoastrocytomas and therefore it needs to be identified and treated separately.

Bronchial salivary gland-type intraductal carcinoma with KIAA1217::RET gene fusion composed of intercalated and oncocytic components.

Salivary gland-type intraductal carcinoma (IC) is a rare malignant salivary gland neoplasm. Primary salivary gland-type IC has never been described in the lung. Herein, we present a primary pulmonary IC in a 63-year-old woman. The tumor originated in the bronchus wall of the right middle lobe. The tumor consisted of two histological types, intercalated component and oncocytic component. The intercalated component showed tubular/cystic pattern composed of column to cube-shaped cells and scattered mucous cells. The oncocytic component showed solid nests composed of large cells with abundant eosinophilic granular cytoplasm. Immunohistochemically, both histological components were positive for cytokeratin 7 (CK7), S-100 protein, SOX10, and mammaglobin. The rimming myoepithelial cells were highlighted by p63 and smooth muscle actin (SMA). The tumor cells were negative for androgen receptor (AR), HER-2, Dog-1, TTF-1, napsin A, GCDFP-15, and GATA3. In the present case, we detected KIAA1217::RET fusion via DNA-based next-generation sequencing (NGS) and RT-PCR, which established the diagnosis of IC at a molecular level. The present case expands the categories of bronchopulmonary salivary gland-type tumors.

FNA as a Powerful Modality to Detect Granular Cell Tumor in Male Breast: A Report and Review of Literature

Abstract Introduction/Objective Granular cell tumor (GCT) is a benign mesenchymal tumor of Schwannian origin. Granular cell tumor is an uncommon tumor of the breast with a prevalence of 1:1000 to 6.7:1000 of all breast tumors. Most cases are diagnosed on surgical resection. When reported that are most commonly in middle-aged premenopausal women. Diagnosis of GCT on fine needle aspiration (FNA) in male patients is, however, extremely rare. We present here an unusual case of GCT of the breast in a male patient clinically mimicking malignancy. Methods/Case Report A 34-year-old male patient presented with a palpable lump in the left breast. An imaging study showed a 0.6 cm hypoechoic mass with microlobulated borders and no internal vascularity suspicious for breast carcinoma (BIRAD-4). Fine needle aspiration (FNA) of the mass was performed. Rapid onsite specimen evaluation was performed and additional passes were performed to collect sample for cell block to perform ancillary studies. FNA revealed clusters of polygonal cells with abundant eosinophilic granular cytoplasm and poorly defined borders. Those cells had round to ovoid nuclei with vesicular chromatin pattern and prominent nucleoli. A differential diagnosis of GCT, apocrine metaplasia, and lesions rich in histiocytes such as granulomatous inflammation, fat necrosis and duct ectasia were considered. Immunohistochemical staining with S100 and CD68 was performed which stained granular cytoplasm in tumor cells of GCT. A review of literature from the past 5 years shows 23 cases of GCT of the breast are reported in the literature and of these only 3 (13%) are reported in males. These tumors ranged from 20-68 years with tumor size ranging from 5- 28 mm. Only 1(4%) cases were preoperatively diagnosed using FNA. No cases of GCT were preoperatively diagnosed on FNA samples from the breast. Results (if a Case Study enter NA) N/A. Conclusion We show here that a powerful relatively noninvasive and rapid modality like FNA can be effectively utilized to detect very rare benign tumor like GCT in the male breast where imaging studies suspect breast cancer.

S-100 Negative Granular Cell Tumor of Oral Cavity with Aggressive Clinical Behavior

Abstract Introduction/Objective Granular cell tumors (GCTs) are neoplasms with neuroectodermal (Schwann cell) differentiation that is typically benign and cured by surgical excision. These tumors characteristically display strong expression of S-100 protein. Similar tumors without expression of S-100 protein are called “S-100 negative granular cell tumors.” The few reported cases of S-100 negative GCT in the oral cavity describe indolent clinical behavior. We report a case of a 49-year-old male with recurrent S-100 negative GCT in the oral cavity. Methods/Case Report The patient presented initially with a mass in the hard palate, which was resected and diagnosed as an S-100 negative GCT. One year later, the patient developed severe epistaxis and anemia (hemoglobin 7.2 g/dL). A large tumor of the hard palate was the source of bleeding. It was resected and diagnosed as recurrent S-100 negative GCT. Histologically, this tumor consists of small nests of epithelioid to spindled cells with moderately abundant granular eosinophilic cytoplasm, round central nuclei with vesicular chromatin and distinct eosinophilic nucleoli, and significant mitotic activity. The cells are immunoreactive for SOX10 and negative for S-100, melan-A, keratin AE1/AE3, p40, synaptophysin, smooth muscle actin, desmin, and myogenin. Results (if a Case Study enter NA) N/A Conclusion S-100 negative GCTs are rare, and only a few case reports describe their involvement in the oral cavity. We report this case because of its rarity and aggressive clinical behavior. Recognition of this entity and its potential for locally aggressive growth is important. Management of this tumor by complete excision seems advisable.

An intriguing journey of encapsulated apocrine papillary carcinoma of the breast

BackgroundEncapsulated Apocrine Papillary Carcinoma (EAPC) of the breast are very rare tumors. They usually present as a cystic mass with mural nodule in women aged 44–84 years. Affected patients may be asymptomatic or complain of breast swelling, or nipple discharge. Mammographic features are nonspecific. The tumor appears as a high-density round or oval mass with circumscribed or spiculated margins on mammography. On Ultrasonography (US) a classical lesion appears as predominantly cystic mass with intracystic solid papillary projections and area of vascularity within it. Contrast Enhanced Breast MRI helps to further characterize the lesion by showing intense contrast enhancement in early phase along with washout curve. Histological features of these tumors are similar to those of classical encapsulated papillary neoplasm, in that myoepithelial cells are absent within the papillary structures and at the periphery of the cyst. They show variable degree of cytological atypia and mitotic activity. Such tumors consist of abundant granular eosinophilic cytoplasm and large nuclei with prominent nucleoli and are androgen receptor positive. However, a multidisciplinary approach is crucial for diagnosis and tissue histology is essential to suitably formulate treatment guidelines. Surgical excision is the preferred treating option for these tumors. Little consensus is available about local radiation and adjuvant therapy for the treatment of such tumors, yet they have been reported to have good prognosis.Case presentationThis rare case report describes the intriguing journey towards the diagnosis of an encapsulated intracystic apocrine papillary carcinoma in a 52-year-old premenopausal female who presented with palpable breast swelling in left breast. The patient underwent mammography, breast ultrasound and breast MRI concluding it to be a BIRADS 4A lesion. Then the patient was subjected to trucut core biopsy and finally surgical excision was performed. On Histopathology this lesion was diagnosed as encapsulated apocrine papillary carcinoma with androgen receptor positivity and triple negative hormonal status. At present patient is on regular follow-up.ConclusionsEncapsulated intracystic apocrine papillary carcinoma has a favorable prognosis with low recurrence rate and excellent long-term survival regardless of its invasive nature. Therefore, we present this rare entity to highlight the importance of radiological and histopathology findings in its diagnosis.

Sine Qua Non: Oncocytoma.

Oncocytomas of the salivary gland are uncommon neoplasms that are characterized by polygonal cells with abundant granular eosinophilic cytoplasm and relatively uniform nuclei. They are benign in nature and have a low recurrence rate with complete surgical excision. Though uncommon, oncocytic and clear cell variants of malignant tumors may histologically mimic oncocytomas and identification of their distinguishing features is essential. A classic example of an oncocytoma is discussed.

Ovarian and paraovarian adrenal rest tumors are not uncommon in gonadectomy materials of historical congenital adrenal hyperplasia cases in childhood.

The aim of this study was to assess the prevalence of ovarian and paraovarian adrenal rest tumors (ARTs) in gonadectomy materials of a subgroup of congenital adrenal hyperplasia (CAH) patients. A total of 20 historical cases with clinical/molecular diagnosis of classical CAH were included in the study. All patients had 46,XX karyotype and underwent gonadectomy because of being raised as male. Median age at diagnosis of CAH was 5.7 years and was markedly delayed. All patients revealed severe virilization. Bone age was significantly advanced, and bone age/chronological age ratio was increased with a median ratio of 1.8. Median age at the time of gonadectomy was 9.2 years. Ovarian and paraovarian ARTs were detected during the pathological evaluation of gonadectomy materials in four patients (20%) (two with simple virilizing 21-hydroxylase and two with 11-beta-hydroxylase deficiency) with previously normal pelvic imaging. In three cases with ARTs, paraovarian area was composed of medium-sized polygonal cells, with round or oval monomorphic nuclei and abundant granular eosinophilic cytoplasm which is characteristic of adrenocortical tissue. The fourth case had bilateral ovarian 'steroid cell tumors, not otherwise specified', and the tumor was accepted as benign. Except for the ARTs, heterotopic prostate and bilateral paratubal epididymis tissue were detected in a patient. Ovarian and paraovarian ARTs might be more common than previously described, especially among patients with excessive and prolonged adrenocorticotropic hormone exposure. These tumors could be detected histopathologically even if not detected by classical imaging methods.

Melanotic Oncocytic Metaplasia of the Nasopharynx Seen as a Rare Form of Cystic Mass: A Case Report and Review of the Literature

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare benign lesion which is characterized by the presence of usually a small, pigmented lesion near the Eustachian tube opening, but never reported the form of cyst without pigmentation. A 76-year-old man who had a symptom with globus pharyngeus for 3 months was presented to otolaryngology clinic. The lesion was found as a rare form of cystic mass without pigmentation through endoscopic examination. Microscopically, there were well-formed glandular structured oncocytic cells with abundant eosinophilic granular cytoplasm. Scattered brown pigments were also noted, which were positive for S-100 and negative for HMB-45 in immunohistochemistry. He was diagnosed with MOM of the nasopharynx. MOM of the nasopharynx should be always taken into consideration about its various clinical forms as a benign mimicker of malignant melanoma.

Warthin like Variant of Papillary Thyroid Carcinoma: A Rare Variant

Introduction: Warthin like papillary thyroid carcinoma is a rare variant that bears features similar to Warthin tumour of salivary gland. It shows papillary or follicular structures lined by oncocytic cells having typical nuclear features of papillary thyroid carcinoma and marked lymphoplasmacytic infiltrate in the stroma. Case Report: A 60 year old lady presented in the ENT OPD with right sided neck swelling since 2 years. On examination the swelling was firm, non-tender, moving with deglutition and measured 4x3 cm. FNA smears of the swelling were highly cellular and comprised of cells arranged in papillary clusters. The cells were predominantly oncocytic and showed nuclear grooving and intranuclear inclusions. Cytological diagnosis of papillary thyroid carcinoma (Bethesda Category VI) was offered. Thyroidectomy specimen measured 6.5x5x3 cm and right lobe revealed gray tan tumor with numerous papillae and few cystic areas. Microscopy revealed a well circumscribed tumour, with tumour cells arranged in papillary architecture with presence of dense lymphoplasmacytic infiltrate in the stalks of papillae. The cells lining the papillae had abundant granular eosinophilic cytoplasm and many of the cells showed nuclear grooving and intranuclear inclusions. Occasional psammoma bodies were also seen. The surrounding thyroid showed features of hashimoto’s thyroiditis. A final diagnosis of Warthin like variant of papillary thyroid carcinoma was given. Conclusion: Warthin like variant of papillary thyroid carcinoma is a distinct rare variant. It is associated with good prognosis when compared with other variants of papillary thyroid carcinoma, warranting a proper identification.

S1867 Rectal and Esophageal Granular Cell Tumors; A Report of Two Cases

Introduction: Granular cell tumors (GCT) are a predominantly benign tumor arising from mesenchymal origin - specifically Schwann cells. They typically appear as a solitary mass; in the gastrointestinal tract (GIT), they can present as a painless yellow-gray polyp or nodule. It is more commonly found in women ages 10-50 years old. They can arise in any location, most commonly from the skin, and only 10% found in the GIT. Within the GIT, the esophagus is the most common location while the rectum is the rarest location. Case description/methods: Case #1: Patient is a 51-year-old female with no significant past medical history coming in with right upper quadrant (RUQ) abdominal pain. Pain has been present for 1 month prior to seeking medical attention. Pain is not consistently associated with eating food. There is no associated nausea, vomiting, diarrhea, or constipation. EGD was performed at that time and revealed a white localized plaque (image 1A). Histopathology on H&E stain revealed esophageal mucosa with underlying sheets of epithelioid cells with abundant granular eosinophilic cytoplasm (image 1B). S100 stain was positive, but MART1 and SOX10 were negative. Case #2: Patient is a 64-year-old male with a past medical history significant for aortic stenosis who presented for his first screening colonoscopy. At that time, colonoscopy revealed mild erythematous mucosa in the terminal ileum and sigmoid colon as well as a small mass in the rectum (image 1C). Biopsy results revealed focal active colitis in the sigmoid colon and a rectal granular cell tumor in the rectum. Histopathology of the tumor revealed colorectal mucosa with packets of uniform epithelioid cells with abundant eosinophilic granular cytoplasm interdigitating with the colonic crypts on H&E stains (Image 1D). S100 immunohistochemistry stain demonstrated diffuse expression within the granular cell tumor with absent staining in crypt epithelium (Image 1E-F). MART1 and SOX10 were negative as well. Discussion: GCTs are rare tumors ad account for 0.5% of all soft tissue tumors. Only 10% occur in the GIT and rarely in the rectum. Most are benign with only 1-2% being malignant. If ulceration is found, malignancy should be ruled out. It is also important to differentiate them from other tumor occurring in the GIT such as neurogenic and gastrointestinal stromal tumors. It is also important to differentiate them from melanomas as they stain positive for S100; melanoma specific stains, such as MART1 and SOX10, are used to differentiate them.Figure 1.: (A) White localized plaque in the esophagus. (B) Esophageal mucosa with underlying sheets of epithelioid cells with abundant granular eosinophilic cytoplasm. (C) Small yellowish mass in the rectum. (D) H&E stain revealing colorectal mucosa with packets of uniform epithelioid cells with abundant eosinophilic granular cytoplasm interdigitating with the colonic crypts. (E) S100 immunohistochemistry stain demonstrating diffuse expression within the granular cell tumor with absent staining in crypt epithelium. (F) Rectal granular cell tumor negative for MART1 and SOX10 at 20x magnification.

MULTIFOCAL PULMONARY GRANULAR CELL TUMOR

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Granular cell tumors, also known as Abrikossoff tumors, are a rare group of Schwannian neoplasms typically found in the skin and tongue, but also occur in the lung. Granularity of the cells is due to accumulation of secondary lysosomes in the cytoplasm. Only 0.5-2% of pulmonary granular cell tumors (pGCT) are malignant, but some benign cases show similar behavior. Here, we describe a diagnostically challenging case of multifocal pGCT. CASE PRESENTATION: A 48-year old male with history of asthma, chronic obstructive pulmonary disease, hypertension, and alcoholic steatohepatitis presented for evaluation of a right lung mass found on chest X-ray 5 years ago. He endorsed progressive dyspnea poorly controlled with beclomethasone and albuterol inhalers. He had history of tobacco smoking with 31 pack-years, as well as alcohol abuse. He worked in a shipyard for 3 years with exposure to asbestos and welding fumes. Computed tomography of the chest showed a 4.1-cm solid mass in the right lower lobe, as well as a 1.1-cm endobronchial lesion in the right bronchus intermedius, multiple left lower lobe lesions, and mediastinal lymphadenopathy. Spirometry showed moderate obstructive disease with bronchodilator response. Biopsies of lower lobe and tracheal mucosal lesions obtained by bronchoscopy revealed sheets of epithelioid cells with abundant eosinophilic granular cytoplasm and small uniform nuclei consistent with pGCT. There was no evidence of necrosis or increased mitotic figures to suggest malignancy. Immunostaining was positive for S100, CD68, SOX10, inhibin, and PAS. He was referred to Interventional Pulmonology for laser debulking and endobronchial stenting. DISCUSSION: Determining whether pGCTs are malignant or benign can be challenging. Both types occur in all age groups. Both can cause dyspnea, cough, and pleuritic chest pain. Large tumor size is not predictive, as many malignant pGCT's are <4 cm at time of diagnosis. Additionally, 20% of benign pGCTs have multiple lung lesions. However, the presence of extrapulmonary metastases is diagnostic of malignancy. Malignant pGCTs also show 3 or more histologic features of the Fanburg-Smith criteria, including necrosis, spindling, pleomorphism, vesicular nuclei with large nucleoli, high nuclear/cytoplasmic ratio, and increased mitotic activity. Positive p53 or Ki67 immunostaining can indicate malignancy in indeterminate cases. Management of benign pGCTs is surgical. Small tumors <1.0 cm may be removed by bronchoscopic extirpation, laser therapy, or sleeve resection. Larger tumors are resected surgically. Prognosis for benign pGCT is good (2-8% recurrence) if complete margin-free removal is achieved. CONCLUSIONS: Malignant and benign pGCTs share many features that make them difficult to differentiate. Absence of extrapulmonary metastases, Fanburg-Smith criteria, and specific immunostaining helps rule out malignancy in cases with multifocal lung lesions. REFERENCE #1: Jiang M, Anderson T, Nwogu C, Tan D. Pulmonary malignant granular cell tumor. World J Surg Oncol. 2003;1(1):22. Published 2003 Oct 21. doi:10.1186/1477-7819-1-22. REFERENCE #2: Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG. Malignant granular cell tumor of soft tissue. Diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol. 1998;22:779–794. doi: 10.1097/00000478-199807000-00001. REFERENCE #3: Khansur T, Balducci L, Tavassoli M. Granular cell tumor: clinical spectrum of the benign and malignant entity. Cancer. 1987;60:220–222. DISCLOSURES: No relevant relationships by Ramiz Fargo, source=Web Response No relevant relationships by Joseph Mak, source=Admin input No relevant relationships by Bryce Mikel, source=Web Response

Granular Cell Tumor of the Breast: Clinical Presentation, Pathological Diagnosis and Treatment

Introduction: Granular cell tumor is a rare neoplasm of soft tissue and only in 1% of cases, it can shows a malignant behaviour. It is presumed to be a tumor originating from perineural or putative Schwann cells of peripheral nerves. Materials and Methods: We reviewed five patients affected by Granular cell tumor of the breast treated between January 2011 and January 2021 at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome, Italy. Results: All of the granular cell tumors presented as solitary, painless and firm lump, highly suggestive of malignancy. The radiological findings were heterogeneous and non-specific. All lesions presented as masses, more clearly evident on ultrasound as hypoechoic lesions, with irregular shape, blurred contours and borderline features. The tumors were composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei, being immunohistochemically positive for S100, Vimentin (with variable staining), CD56; negative for HMB45, MelanA, AE1/AE3, EMA, and Desmin. Conclusion: Granular cell tumor is a rare, usually benign breast disease that can have very similar characteristics to breast cancer both clinically and radiologically. Treatment of choice consists in wide resection or lumpectomy with margin assessment (no ink on tumor).

A case report of fibrolamellar hepatocellular carcinoma, with particular reference to preoperative diagnosis, value of molecular genetic diagnosis, and cell origin

BackgroundFibrolamellar hepatocellular carcinoma (FL-HCC) is a liver tumor that occurs almost exclusively in young adults without underlying liver disease. In spite of its distinct clinical characteristics and specific imaging findings, preoperative diagnosis is often difficult due to the extremely low incidence of the tumor. Although FL-HCC shows particular morphological features on H&E-stained tissue sections, differential diagnosis from ordinary HCC, especially the scirrhous variant of HCC, and intrahepatic cholangiocarcinoma needs additional immunohistochemical (IHC) analyses and/or molecular genetic testing.Case presentationA 21-year-old male patient was referred to our hospital for further evaluation of a large liver mass. Abdominal ultrasound examination, contrast-enhanced computed tomography, and magnetic resonance imaging revealed a well-defined hypervascular lobulated liver mass, 11 × 11 cm in diameter, with a central scar and calcification, in segments 5/8. Under the diagnosis of FL-HCC, we carried out extended anterior sectorectomy, including a part of segment 4. On microscopic examination, the tumor was composed of proliferating polygonal cells with abundant eosinophilic granular cytoplasm containing nuclei with vesicular chromatin and enlarged nucleoli, in an abundant stroma. Collagen fibers arranged in a parallel lamellar pattern were seen in the tumor stroma. These findings, together with the results of subsequent IHC analyses using HAS, CK7, and CD 67, we made the diagnosis of FL-HCC, which was further confirmed by detection of the DNAJB1-PRKACA fusion gene in the tumor cells by RT-PCR.ConclusionFL-HCC shows distinct imaging appearances. Although it also has characteristic morphological features, combined use of IHC and/or molecular genetic studies are necessary for the final diagnosis.