Abundant Granular Cytoplasm Research Articles

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.

Apocrine adenocarcinoma of the breast: A rare special subtype with divergent theranostic markers

ABSTRACT Carcinoma of the breast with apocrine differentiation also known as apocrine adenocarcinomas is special histological subtypes comprising approximately 1% of breast cancers. They are estrogen receptor/progesterone receptor-negative and androgen receptor-positive tumors having more than 90% population of tumor cells with apocrine morphology. We present a 49-year-old woman with a breast lump in the right upper outer quadrant clinically and radiologically diagnosed as malignancy and histologically proven as apocrine adenocarcinoma of the breast owing to the morphology comprising tumor cells having abundant granular cytoplasm, central to the eccentric nucleus and prominent nucleoli. On immunohistochemistry, it was a triple-negative tumor with AR positivity. As apocrine adenocarcinoma of the breast has an uncertain prognosis, variable HER2/neu overexpression, debatable responses to neoadjuvant therapy, and probable response to androgen therapy, the onus of diagnosing and reporting these tumors accurately lies with the pathologist. Moreover, as the presentation of these tumors is similar to invasive breast carcinoma, no special type but with potentially different and useful theranostic markers, an emphasis on specifying this histological subtype is becoming increasingly essential.

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.

Dermal nonneural granular cell tumor: a case report

Dermal nonneural granular cell tumor is a rare neoplasm of uncertain histogenesis that Le Boit and colleagues originally described in 1991. It arises commonly from the back, extremities and head and neck. To the best of our knowledge, only 50 cases have been reported in adults in the English literature. A 42-year-old man presented with a polypoid skin nodule of the front side of the chest wall, measuring 1,8 × 1,5 cm. The lesion was removed completely with tumor-free margins. Microscopically, the tumor was composed of a diffuse infiltrate of polygonal cells, S 100 negatives, with abundant granular cytoplasm and vesicular nuclei. The diagnosis of dermal nonneural granular cell tumor was retained. No recurrence was noted during follow up of 6 months. The prognosis is good.

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.

Oncocytic Lesion or an Atypical Epithelioid Vascular Tumor of Unknown Biologic Potential: A Rare Diagnostic Dilemma

<h3>Introduction</h3> Oncocytomas are rare benign tumors found in many different organs, including but not limited to the kidneys, thyroid, parathyroid and salivary glands. Oncocytomas arising in the minor salivary glands are rare. These tumors represent 1 to 2% of all salivary gland neoplasms. <h3>Materials and Methods</h3> We report a case of a 16 year old female patient who was referred to an oral surgeon due to an incidental finding of a soft palatal mass while evaluating for pain in the maxillary area. The soft palatal mass was asymptomatic. The patients past medical history was non-pertinent. <h3>Results</h3> PET scan failed to identify the clinically observed palatal mass. Microscopically, there was a proliferation of large polygonal epithelioid cells forming loosely cohesive, vaguely organoid structures associated with promi- nent dilated and convoluted vascular spaces and demonstrated an infiltrative growth pattern in some areas. These cells showed abundant granular cytoplasm and an eccentrically placed nuclei, including nuclear pseudoinclusions. Mitotic activity or necrosis was not seen. Histologically, the morphology also somewhat mimicked a rhabdoid tumor but rhabdoid tumors are not usually so prominently vascular and are aggressive but in our case Ki-67 proliferation index was scant, besides INI 1 or SMARCB1 expression was not lost on IHC ruling out the possibility of SMARCB1 negative tumors. ERG stain was negative in the tumor cells but delineated the vascular lobules encompassing the polygonal cells. PTAH was diffusely positive in the polygonal epithelioid appearing cells suggestive of a mitochon- drial (oncocytic) component characterizing the cellular proliferation. The tumor cells exhibited a strong positivity for Vimentin and were moderately reactive for Pancytokeratin which necessitated the need to rule out metastatic carcinoma. <h3>Conclusion</h3> Our case showed a propensity towards rhabdoid cytomorphology but without loss of SMARCB1/INI1 protein expression emphasizing the clinical efficacy of INI1 IHC in discerning these tumors in the differential.

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.

Unexpected endometrial malakoplakia in a 74-year-old-female: A case report

Abstract Introduction/Objective Malakoplakia is a chronic inflammatory disease, usually associated with bacterial infection. The urinary system is the most commonly involved site. Involvement of the female genital tract is extremely rare. Histopathologically, the disease is manifested by solid sheets of histiocytes with abundant granular eosionophilic cytoplasm, and intra- and extracellular basophilic bodies. It should be differentiated from other types of granulomatous inflammation and from signet ring cell carcinoma. Treatment consists of antibiotics, but surgery is sometimes necessary. Methods/Case Report A 74-year-old woman experienced postmenopausal bleeding for several years. A previous endometrial biopsy showed a mucinous glandular proliferation of uncertain etiology. She also had coronary heart disease, hypertension, diabetes mellitus and hyperlipidemia. A prior urinalysis showed abundant bacteria, and she had been hospitalized recently for urinary tract infection (UTI). She underwent laparoscopic total hysterectomy. Grossly, the endometrium was mostly uniform, 0.1 cm in thickness, with one 0.4-cm polyp. Microscopically, the endometrium showed simple hyperplasia without atypia, benign endometrial polyp, and multifocal malakoplakia, manifested by sheets of histiocytes with granular eosinophilic cytoplasm, many of them containing variably-sized basophilic spherules imparting to them a targetoid, or bull’s eye, appearance. Multiple endometrial plasma cells were also seen. Results (if a Case Study enter NA) NA Conclusion Very few cases of endometrial malakoplakia have been reported in the medical literature. Here we present unexpected malakoplakia coexisting with endometrial simple hyperplasia without atypia. Reports from the electron microscopy literature suggest that the basophilic spherules, named Michaelis-Gutmann inclusion bodies, are electron-dense granules that result from coalescence of phagolysosomes, reflecting failed digestion of bacteria. In our patient, longstanding chronic endometritis, confirmed by the presence of endometrial plasma cells, possibly coexisting with chronic UTI, culminated in malakoplakia, which clinically and pathologically mimicked endometrial hyperplasia or even carcinoma, given her old age, chronic bleeding, and the mucinous epithelium in the endometrial biopsy. The finding of endometrial malakoplakia should remind us of the bacterial etiology of chronic endometritis and the need for timely treatment of urogenital infections with antibiotics.

Synchronous bilateral pheochromocytomas and extra-adrenal paragangliomas without specific gene mutations

Abstract Introduction/Objective Diagnosis of hereditary paraganglioma-pheochromocytoma syndrome (H-PGL/PCC-S) should be suspected in individuals with pheochromocytoma or paraganglioma, especially those with multifocal lesions, positive family history, or early-onset disease. Recent studies suggest one-third to half of these patients have germline/syndromic associations. We present a challenging case wherein a 44-year-old female with high-risk factors, multiple paragangliomas, and bilateral pheochromocytomas did not have any identifiable syndromic involvement. Methods/Case Report Patient presented seven years ago with epigastric pain, weight loss of 50lbs, and chronic diarrhea. Endoscopic ultrasound revealed 2cm hypoechoic mass behind pancreas, diagnosed as neuroendocrine tumor on fine-needle aspiration. Subsequent SPECT-CT and MRI revealed multiple intra-abdominal lesions, including bilateral adrenal-lesions (right 2cm; left 1.6cm), 2.2cm aortocaval-lesion, and multifocal retroperitoneal lesions, consistent with paragangliomas, gradually increasing in size on follow-up imaging. She also developed intermittent palpitations, flushing, and blood pressure fluctuations. Additionally, multiple thyroid nodules were identified on subsequent ultrasound imaging, suspicious for malignancy on both cytology and Afirma studies. Exploratory laparotomy with left para-adrenal, right infra-renal, and aortocaval nodule-excisions revealed nested tumor cells with abundant granular purple cytoplasm, round central nuclei, prominent nucleoli, diagnosed as moderate to poorly differentiated extra-adrenal paragangliomas with increased metastatic risk based on PASS and GAPP-scoring systems. Additionally, right adrenalectomy revealed pheochromocytoma with 7/20 PASS-score and 4/10 GAPP-score suggesting increased metastatic risk. Results (if a Case Study enter NA) NA Conclusion Young age, strong family-history, multiple high-grade paragangliomas, pheochromocytomas, and suspicious thyroid nodules raise concerns for syndromic association. Multitude of autosomal-dominant syndromes, including paraganglioma-syndromes (PGL1-to PGL5), VHL, MEN2A, MEN2B, and NF1, have been reported. Genes identified in these syndromes include SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX, TMEM127, VHL, NF1, RET, FH, and KIF1B. However, no mutations were identified, thus creating a dilemma in risk-stratification. This leaves out only two considerations: either sporadic PGL/PCC or a yet unidentified genetic-mutation.

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.

Oncocytic Adrenocortical Carcinoma With Low 18F-FDG Uptake and the Absence of Glucose Transporter 1 Expression

Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia.

Medullary thyroid carcinoma a relatively uncommon entity: A case report

Introduction: Medullary thyroid carcinoma is an uncommon primary thyroid tumour (5-10% of all thyroid malignancies) arising from parafollicular cells or C-cells. Most tumours are sporadic (75-80%) and familial syndrome multiple endocrine neoplasia; MEN-2A, MEN-2B and familial MTC in 20 to 25% cases. Case Report: We report a case of primary medullary thyroid carcinoma in a 30 years old male patient presented with complaint of midline neck swelling. On fine needle aspiration cytology diagnosis of medullary carcinoma was suggested with a differential of SETTLE (spindle epithelial tumor with thymus like differentiation). The swelling was excised and send for histopathological examination which revealed polygonal to plump spindle shaped tumor cells, arranged in lobules separated by fibrous septa, having abundant eosinophilic granular cytoplasm with round to oval nuclei, finely stippled nuclear chromatin and indistinct nucleoli and diagnosed as primary medullary thyroid carcinoma, confirmed on immunohistochemistry. Conclusion: MTC is the first human malignancy known to be associated with tumour marker and hormone calcitonin. Immunohistochemistry has definite role in confirmation of diagnosis. Keywords: Amyloid, Medullary carcinoma, Procalcitonin, Synaptophysin.

Salivary Duct Carcinoma arising from pre-existing Epithelial-Myoepithelial Carcinoma of the parotid gland: Another rare example with Cytological Correlation

An extremely exceptional case of salivary duct carcinoma (SDC) arising from pre-existing epithelial-myoepithelial carcinoma (EMC) of the parotid gland is herein described. The patient was a 50-year-old Japanese female, who presented with an asymptomatic mass of the right parotid gland that had been present for approximately 7 years. A superficial lobectomy of the parotid gland was performed and there have been no symptoms of recurrence or distant metastasis during over 10-year follow-up period. Histologically, the tumor was composed of an EMC component having double-layered ducts and invasive nests of myoepithelial clear cells with an SDC component intermingled throughout the lesion, which consisted of eosinophilic pleomorphic cells. Nests of the SDC component were occasionally accompanied by small luminal structures and minimally focalized comedo necrosis, and were immunoreactive for androgen receptor and GCDFP15. Fine needle aspiration cytology showed moderate cellularity, a few three-dimensional or sheet-like clusters, and single dispersed cells with abundant granular cytoplasm in the background. Furthermore, hyperchromatic small or flattened cells were identified attaching to the periphery of the clusters in retrospective observation. Metachromasia was also seen in May-Grunwald Giemsa stain. Keywords: Salivary duct carcinoma; Epithelial-myoepithelial carcinoma; Parotid gland; Dedifferentiation; High-grade transformation; Fine needle aspiration cytology

TSC/MTOR-mutated eosinophilic renal tumors are a distinct entity that is CK7+/CK20-/vimentin-: a validation study

Unclassified renal cell carcinoma (RCC) accounts for ∼10% of renal tumors, and the most common histologic findingin these cases is eosinophilic cytoplasm. We previously demonstrated that a subset of eosinophilic renal tumors with heterogeneous morphology and immunohistochemical (IHC) staining harbored pathogenic mutations in tuberous sclerosis complex (TSC) or mammalian target of rapamycin (MTOR) as the primary defining mutation. We identified an additional 8 cases of eosinophilic tumors with unusual morphology that were originally diagnosed as chromophobe RCC (CHRCC) or CHRCC, eosinophilic variant. As a comparison, we included four classic CHRCC cases and one CHRCC, eosinophilic variant case. Gross examination revealed solid or solid and cystic patterns. The solid areas were composed of eosinophilic tumor cells divided by congested vessels, whereas the cystic areas were lined by cytologically bland eosinophilic cells with septae containing nests, ribbons, and single eosinophilic tumor cells. The tumor cells had abundant granular eosinophilic cytoplasm with round nuclei and inconspicuous nucleoli. IHC analysis demonstrated diffuse staining for CK7 and negative staining for CK20 and vimentin. Next-generation sequencing identified pathogenic variants in three genes: TSC1, TSC2, and MTOR. They also lacked significant copy number variations in contrast to our control cases. We have demonstrated with our expanded study that cases previously diagnosed as CHRCC or CHRCC, eosinophilic variant with discordant histology and IHC staining patterns may represent a separate subtype of RCC characterized by mutations in the TSC/MTOR pathway.

Skin Manifestation Associated With Multicentric Reticulohistiocytosis.

Multicentric reticulohistiocytosis (MRH) is a rare multisystem disorder, primarily affecting the skin and joints. As severe joint damage is a possible symptom, early diagnosis and therapeutic intervention are required. Cutaneous lesions present with characteristic features such as discrete reddish nodules, especially on acral locations. Additionally, the face, scalp, trunk and extremities are also affected. Xanthomatous plaques are also seen on the face. The cutaneous manifestations of MRH are various, which therefore should be differentiated from several diseases. In particular, MRH has been reported to assume clinical appearances resembling Gottron papules, periungual erythema, V-neck erythema, shawl sign, and poikiloderma associated with dermatomyositis. Histopathologic features show proliferation of multinucleated giant cells with abundant eosinophilic granular ground glass-like cytoplasm in the dermis. Multicentric reticulohistiocytosis is occasionally paraneoplastic and is associated with internal malignancies. The appropriate therapies are still challenging, and oral prednisolone, immunosuppressants, and recent biologics are used. In this article, cutaneous lesions, histopathology, and pathogenesis of MRH are mainly discussed from a dermatological perspective. It is important, not only for dermatologists but also for rheumatologists and orthopedists, to be able to distinguish between the various types of skin lesions brought on by MRH. Cutaneous signs are important diagnostic clues and assessment tools for therapeutic efficacy.

Case Report: Malakoplakia Developing in the Graft Colon Post Intestinal Transplant

Abstract Casestudy Malakoplakia is a rare chronic granulomatous disease thought to be caused by a macrophage bactericidal defect and most commonly affecting the genitourinary tract. Most cases are associated with chronic infections or immunosuppression, with most transplant related cases observed after renal transplantation. Results A male in his thirties developed short gut syndrome secondary to injuries and subsequently underwent a small and large bowel transplant and was treated with immunosuppressive medications. He developed multiple episodes of acute rejection and multiple infectious foci, including a peri-rectal fluid accumulation growing Escherichia Coli, bacteremia with Klebisella oxytica, and Epstein Barr Virus viremia. Functional imaging revealed increased activity in mesenteric lymph nodes and in the peri-rectal fluid accumulation. On endoscopy, a rectal ulcer associated with mucosal protuberance was noted and tissue was obtained for pathologic diagnosis. Histologic examination revealed mucosal infiltration by numerous macrophages with abundant granular cytoplasm. Michaelis-Gutmann bodies (considered pathognomonic for malakoplakia) were identified showing PAS and Von- Kossa positivity. Acid fast stain was negative. These findings supported the diagnosis of malakoplakia. Other differential diagnoses were considered, including post-transplant lymphoproliferative disorder, neoplasia, infection with mycobacterial or fungal species, and secondary hemophagocytic lymphohistiocytosis syndrome. These were excluded based on the characteristic histologic findings. Given the diagnosis, treatment with oral antibiotics was attempted. Follow up biopsies revealed disease persistence and the patient was transitioned to a prolonged course of intravenous antibiotics and bethanechol, with eventual histologic response. Unfortunately, due to stenosis and adhesions that developed secondary to the episodes of acute rejection, the patient eventually underwent graft explanation. Conclusion Our case highlights the risk factor milieu encountered in intestinal transplant patients and the prolonged treatment often required to treat malakoplakia. Additionally, malakoplakia constitutes an unusual consideration in intestinal transplant patients and prompt diagnosis is required to direct proper management of these patients.