Spindle cell oncocytoma of the neurohypophysis with metastasis to the sphenoparietal sinus and immunohistochemical negativity for S100 and epithelial membrane antigen (EMA).

We report the case of a 61-year-old male with spindle cell oncocytoma of the hypophysis. On presentation to the Department of Neurosurgery at the German Armed Forces Hospital of Ulm, the patient reported a history of several years of left sixth nerve palsy, right ptosis, increased sensitivity to light, and a bilateral retrobulbar pressure sensation. Pituitary function was normal. A chromophobe non-functioning pituitary adenoma was initially suspected. The diagnosis was established on the basis of examination at a histopathology reference laboratory using immunohistochemistry to identify cell surface markers. During two years of follow-up, there were two clinical recurrences requiring surgery. To our knowledge, this is the 35th documented case of spindle cell oncocytoma of the pituitary gland and the first that was immunohistochemically negative for epithelial membrane antigen (EMA) and S100; and the first that displayed haematogenous metastasis to the right sphenoparietal sinus. The three surgical procedures were associated with massive intraoperative bleeding and thus resulted in subtotal tumor resection. Following surgery for the recurrences, the patient underwent radiotherapy.

Growth and renal function dynamics of renal oncocytomas in patients on active surveillance.

OBJECTIVES: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth is associated with renal function over time, the reasons for surgery and ablation, and disease-specific survival. PATIENTS AND METHODS: The study was conducted in a retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at the Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was performed using Mann-Whitney U-tests and chi-squared tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR). RESULTS: Longitudinal data from 98 patients with 101 lesions were analysed. Most patients were men (68.3%) and the median (interquartile range [IQR]) age was 69 (13) years. The median (IQR) follow-up was 29 (26) months. Most lesions were small renal masses, and 24% measured over 4 cm. Over half (64.4%) grew at a median (IQR) rate of 2 (4) mm per year. No association was observed between tumour size and eGFR over time (P = 0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma. CONCLUSION: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow-up of over 2 years. Active surveillance should be considered the 'gold standard' management of renal oncocytomas up to 7cm.

Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature.

BACKGROUND: the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. PROCEDURE: We retrospectively reconstructed an HCC course in five patients < 19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. RESULTS: HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). CONCLUSIONS: (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.

Hürthle Cell Carcinoma in a Lingual Thyroid.

OBJECTIVE: To present a case of lingual thyroid Hürthle cell carcinoma (HCC). CLINICAL PRESENTATION AND INTERVENTION: A 37-year-old female presented with dysphagia and recurrent haemorrhage. Histopathology was suggestive of HCC; the tumour was excised by the trans-glossal approach which provided adequate exposure and helped avert external scarring or mandibular osteotomy. Histopathology showed a tumour-positive right lateral resection margin. This prompted referral to nuclear medicine for radio-iodine ablation. CONCLUSION: Lingual thyroid cases should be followed up closely and fine-needle aspiration biopsy should be considered when in doubt.

Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid.

Oncocytic follicular adenomas (FAs) of the thyroid are neoplasms of follicular cell origin that are predominantly composed of large polygonal cells with eosinophilic and granular cytoplasm. However, the pathological characteristics of these tumors are largely unexplored. Both the initiation and progression of cancer can be caused by an accumulation of genetic mutations that can induce genomic instability. Thus, the aim of this study was to evaluate the extent of genomic instability in oncocytic FA. As the presence of p53-binding protein 1 (53BP1) in nuclear foci has been found to reflect DNA double-strand breaks that are triggered by various stresses, the immunofluorescence expression pattern of 53BP-1 was assessed in oncocytic and conventional FA. The association with the degree of DNA copy number aberration (CNA) was also evaluated using array-based comparative genomic hybridization. Data from this study demonstrated increased 53BP1 expression (i.e., "unstable" expression) in nuclear foci of oncocytic FA and a higher incidence of CNAs compared with conventional FA. There was also a particular focus on the amplification of chromosome 1p36 in oncocytic FA, which includes the locus for Tumor protein 73, a member of the p53 family implicated as a factor in the development of malignancies. Further evaluations revealed that unstable 53BP1 expression had a significant positive correlation with the levels of expression of Tumor protein 73. These data suggest a higher level of genomic instability in oncocytic FA compared with conventional FA, and a possible relationship between oncocytic FA and abnormal amplification of Tumor protein 73.

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies.

CONTEXT: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign. SETTING: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman. PATIENT: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1 mg dexamethasone suppression test. CT scan of the abdomen revealed a 35 mm left adrenal mass. INTERVENTION: The patient underwent a left adrenalectomy, and the histological study showed a 3 cm oncocytic adrenocortical carcinoma with signs of malignancy. RESULTS: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3ßHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery. CONCLUSION: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.

The management of concomitant renal oncocytoma and giant coronary and bilateral common iliac artery aneurysms.

We present the rare case of a 66-year-old Caucasian male patient presenting with intermittent left-side abdominal pain. He underwent a kidneys, ureters, and bladder computed tomography scan on which an incidental 45-mm giant aneurysm of the left anterior descending coronary artery was discovered along with 55-mm right-sided and 62-mm left-sided common iliac artery aneurysms and a 100-mm benign renal oncocytoma. He underwent on-pump coronary artery bypass grafting of the left anterior descending, left circumflex and right coronary arteries using internal mammary artery and saphenous vein grafts. He subsequently underwent simultaneous open left nephrectomy and bilateral common iliac aneurysm repair using a bifurcated tube graft. He made a full recovery postoperatively. Giant coronary artery aneurysms are rare. In the pediatric population, they are predominantly secondary to Kawasaki disease. In adults, atheromatous disease is the leading cause. The coexistence of giant coronary artery aneurysms with extracoronary artery aneurysms is extremely unusual. We propose that the identification of giant coronary artery aneurysms necessitates further imaging investigations to identify the presence of extracoronary aneurysms. To our knowledge, this is the first description of such a case in the literature.

Spectrum of nontumoral renal pathologies in tumor nephrectomies: nontumoral renal parenchyma changes.

Non-neoplastic changes are not rarely seen in renal parenchyma of nephrectomy specimens removed for primary renal neoplasms. These changes often involve both kidneys, thus causing impairment of renal function, reducing patient's quality of life and sometimes threatening it. Renal tissue accompanying the tumor provides an opportunity in order to evaluate these changes. However, the clinician should make available clinical and laboratory findings involving renal functions of the patient to the pathologist. It is also important that the pathologist must have appropriate knowledge and experience in nephropathology. In this study, we aimed to correlate these changes with the clinical data and make inquiries regarding our experience with nonneoplastic kidney pathology. Consecutive 403 nephrectomy specimens with primary renal neoplasms submitted to our department between 2003 and 2009 were re-examined. Twenty-three nephrectomy materials from 21 patients had non-neoplastic changes, 2 of which were bilateral. Patient follow-up data were obtained from electronic medical records. Of all cases, eight had diabetic nephropathy; 2, amyloidosis; 5, segmental proliferative and/or sclerotic glomerulonephritis; and 6, cystic renal changes. These findings were seen in 5% of nephrectomy specimens diagnosed as clear cell renal cell carcinoma (RCC), chromophobe cell RCC and oncocytoma, whereas this rate was two times higher in nephrectomy specimens with papillary RCC. Most patients with renal failure who were diagnosed with clear cell carcinoma died within the first two years. Despite limited number of cases in our series, prognosis of cases with clear cell RCC were poorer. Consequently, we think that non-neoplastic changes should be reported along with the details regarding the tumor in order to achieve best treatment planning.

Parotid gland oncocytoma in HCV-positive patient with non-Hodgkin's lymphoma. Case report.

We report a case of parotid gland oncocytoma in a patient with chronic infection from hepatitis C virus (HCV) and associated non-Hodgkin's lymphoma and xerophthalmia. Our case confirms the triple tropism of the HCV: hepatotropism, lymphotropism and sialotropism.

Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

BACKGROUND: Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. CASE PRESENTATION: The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed "adenoma-like" kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. CONCLUSIONS: Despite well-defined diagnostic criteria and guidelines, diagnosis of MEN1 can still be challenging. When diagnosis is doubtful, appropriate management may be difficult to establish.

Multiple neurilemmomas in Birt-Hogg-Dubé syndrome: case report.

We present a case of a young woman with Birt-Hogg-Dubé syndrome and multiple neurilemmomas involving different nerves in a single extremity. Birt-Hogg-Dubé is an uncommon but increasingly recognized syndrome. Hand surgeons may wish to consider this disease when faced with a patient with multiple neurilemmomas, especially when associated with renal tumors, spontaneous pneumothoraces, or other benign or malignant neural or non-neural tumors.

[Renal oncocytoma in pregnancy--an unusual presentation of secondary hypertension]. / Oncocitoma renal na gravidez--uma forma invulgar de hipertensão secundária.

INTRODUCTION: Renal oncocytoma accounts for 5-7% of primary renal neoplasms. It is usually, diagnosed in asymptomatic patients and is characterized by a benign behavior without invasion of adjacent tissues or metastasis. Diagnosis during pregnancy is uncommon and to date there have been only a few cases reported in the literature. CASE REPORT: The authors present the case of a 32-year-old nulliparous woman with uncontrolled hypertension diagnosed at seven weeks gestation. She was referred to our institution at 24 weeks with superimposed pre-eclampsia complicated by acute pulmonary edema and hemodynamic instability requiring mechanical ventilatory support, fetal growth restriction and stillbirth. Etiological study of the hypertensive disorder performed in the postpartum period was consistent with renal oncocytoma. CONCLUSION: The clinical behavior of renal oncocytoma remains poorly characterized during pregnancy and may lead to an adverse maternal and fetal outcome despite its theoretically benign behavior. It is essential to exclude a possible secondary cause of hypertension in cases that are difficult to control.

[Spontaneous retroperitoneal bleeding caused by rupture of the native kidney oncocytoma twelve years after renal transplantation]. / Spontani retroperitonealni hematom kao posljedica krvarenja iz neprepoznatog tumora nativnog bubrega u bolesnika 12 godina nakon transplantacije bubrega.

Renal transplantation is the method of choice for renal replacement therapy in the majority of patients. Immunosuppressive drugs may increase the risk of developing malignancies. We present a case of a patient having undergone different renal replacement methods over 25 years. He had good graft function at 12 years of transplantation. Development of spontaneous retroperitoneal hematoma caused by rupture of the native kidney oncocytoma was complicated with sepsis and deterioration of graft function. We emphasize the importance of regular ultrasonography follow-up of native kidney, which is challenging because of fibrous changes.

Feminizing adrenocortical oncocytoma presenting as precocious puberty: a case report and literature review.

OBJECTIVES: Feminizing adrenal tumors are rare in childhood. We present a case of a special category of adrenal tumor, an oncocytoma, causing isosexual peripheral precocity. CASE PRESENTATION: A 4-year old girl presented with breast development and menstrual bleeding over a period of 3-4 months. Her SMR staging was breast stage 4, pubic hair stage 3. Her bone age was advanced (6 year 10 months), stimulated LH 0.7 IU/L, estradiol 206 pmol/L and DHEAS >27.1 micromol/L. CT scan revealed a right adrenal mass with features of atypical adrenal adenoma. Laparoscopic adrenalectomy was done and histopathology revealed oncocytoma. Lin-Weiss-Bisceglia criteria classified it as likely benign, borne out till a 2 year follow up. CONCLUSIONS: Adrenal oncocytoma can be a cause of isosexual peripheral precocity in a young girl. Recognition and correct classification of this histological variant, which is more often benign, is important for prognostication and choice of therapy after surgery.

Spindle cell oncocytoma of the pituitary gland with follicle-like component: organotypic differentiation to support its origin from folliculo-stellate cells.

Spindle cell oncocytoma (SCO) is a rare, non-adenomatous tumor originating from the anterior pituitary gland. Composed of fusiform, mitochondrion-rich cells sharing several immunophenotypic and ultrastructural properties with folliculo-stellate cells (FSC), SCO has been proposed to represent a neoplastic counterpart of the latter. To date, however, SCO has failed to meet one criterion commonly used in histological-based taxonomy and diagnostics; that of recapitulating any of FSCs' morphologically defined developmental or physiological states. We describe a unique example of SCO wherein a conventional fascicular texture was seen coexisting with and organically merging into follicle-like arrangements. The sellar tumor of 2.7 × 2.6 × 2.5 cm was transphenoidally resected from a 55-year old female. Preoperative magnetic resonance imaging indicated an isointense, contrast enhancing mass with suprasellar extension. Histology showed multiple rudimentary to well-formed, follicle-like cavities on a classical spindle cell background; while all the participating cells exhibited an SCO immunophenotype, including positivity for S100 protein, vimentin, EMA, Bcl-2, and TTF-1, as well as staining with the antimitochondrial antibody 113-1. Conversely no expression of GFAP, follicular-epithelial cytokeratin, carcinoembryonic antigen, or anterior pituitary hormones was detected. Ultrastructurally, tumor cells facing follicular lumina displayed organelles of epithelial specialization, in particular surface microvilli and apical tight junctions. This constellation is felt to be reminiscent of FSCs' metaplastic transition to follicular epithelium, as observed during embryonic development and physiological renewal of the hormone-secreting parenchyma. Such finding is apt to being read as a supporting argument for SCO's descent from the FSC lineage.

A rare case of progressive ptosis caused by lacrimal gland oncocytoma.

The authors present a case of a healthy 61-year-old woman who presented with a 4-year history of progressive right upper eyelid ptosis. Excisional biopsy revealed malignant oncocytoma, an exceedingly rare tumor of the lacrimal gland.