Browse

You are looking at 1 - 10 of 18 items for :

  • Haematoxylin and eosin staining x
Clear All
Open access

Danielle R Bullock, Bradley S Miller, H Brent Clark and Patricia M Hobday

Summary

IgG4-related hypophysitis is an important diagnostic consideration in patients with a pituitary mass or pituitary dysfunction and can initially present with headaches, visual field deficits and/or endocrine dysfunction. Isolated IgG4-related pituitary disease is rare, with most cases of IgG4-related disease involving additional organ systems. We report the case of a teenage female patient with isolated IgG4-related hypophysitis, diagnosed after initially presenting with headaches. Our patient had no presenting endocrinologic abnormalities. She was treated with surgical resection, prednisolone and rituximab with no further progression of disease and sustained normal endocrine function. This case, the youngest described patient with isolated IgG4-related hypophysitis and uniquely lacking endocrinologic abnormalities, adds to the limited reports of isolated pituitary disease. The use of rituximab for isolated pituitary disease has never been described. While IgG4-related hypophysitis has been increasingly recognized, substantial evidence concerning the appropriate treatment and follow-up of these patients is largely lacking.

Learning points:

  • IgG4-related hypophysitis most often occurs in the setting of additional organ involvement but can be an isolated finding. This diagnosis should therefore be considered in a patient presenting with pituitary abnormalities.

  • Most patients with IgG4-related hypophysitis will have abnormal pituitary function, but normal functioning does not exclude this diagnosis.

  • Corticosteroids have been the mainstay of therapy for IgG4-related disease, with other immunosuppressive regimens being reserved for refractory cases. Further research is needed to understand the effectiveness of corticosteroid-sparing regimens and whether there is utility in using these agents as first-line therapies.

Open access

Xin Chen, Dina Kamel, Braden Barnett, Evan Yung, Adrienne Quinn and Caroline Nguyen

Summary

There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH). Histopathologic findings from such patients who underwent partial/total pancreatomy, however, can vary widely from minimal changes to classic nesidioblastosis, making the pathologic diagnosis challenging. PGBH typically presents as postprandial hypoglycemia, as opposed to insulinoma, which presents as fasting hypoglycemia. Herein, we describe an unusual case of a patient with PGBH who initially presented with postprandial hypoglycemia three years after surgery, but later developed fasting hyperinsulinemic hypoglycemia as the disease progressed. Our hypothesis for this phenomenon is that this disease is progressive, and later in its course, the insulin release becomes dissociated from food stimulation and is increased at baseline. Future studies are needed to investigate the prevalence as well as etiology of this progression from postprandial to fasting hypoglycemia.

Learning points:

  • There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH).

  • Histopathologically, PGBH can vary from minimal changes to nesidioblastosis.

  • Although uncommon, patients with PGBH after Roux-en-Y gastric bypass may present with both postprandial and fasting hyperinsulinemic hypoglycemia as disease progresses.

  • Our hypothesis for this phenomenon is that the insulin release becomes dissociated from food stimulation and is increased at baseline with disease progression.

Open access

Seong Keat Cheah, David Halsall, Peter Barker, John Grant, Abraham Mathews, Shyam Seshadri and Singhan Krishnan

Summary

A frail 79-year-old lady with dementia presented with a 2-year history of frequent falls. Recurrent hypoglycaemic episodes were diagnosed and treated with continuous glucose infusion in multiple hospital admissions. Hypoadrenalism and hypothyroidism were ruled out. Whilst hypoglycaemic (blood glucose 1.6 mmol/L), both plasma C-peptide and proinsulin concentrations, were inappropriately elevated at 4210 pmol/L (174–960) and >200 pmol/L (0–7) respectively with plasma insulin suppressed at 12 pmol/L (0–180). Whilst reported cases of proinsulinoma are typically pancreatic in origin, radiological investigations of the pancreas in this patient did not identify abnormalities. Unexpectedly contrast CT identified a heterogeneously enhancing mass (6.6 cm) at the lower pole of the left kidney consistent with renal cell carcinoma. Non-islet cell tumour-induced hypoglycaemia has been associated with renal malignancy; however, a serum IGF2:IGF1 ratio measured at <10 effectively excludes this diagnosis. Concomitantly on the CT, extensive peripherally enhancing heterogeneous mass lesions in the liver were identified, the largest measuring 12 cm. A palliative approach was taken due to multiple comorbidities. On post-mortem, the kidney lesion was confirmed as clear cell renal carcinoma, whilst the liver lesions were identified as proinsulin-secreting neuroendocrine tumours. In conclusion, the diagnosis of proinsulinoma can be missed if plasma proinsulin concentration is not measured at the time of hypoglycaemia. In this case, the plasma insulin:C-peptide ratio was too high to be accounted for by the faster relative clearance of insulin and was due to proinsulin cross-reactivity in the C-peptide assay. In addition, the concomitant malignancy proved to be a challenging red herring.

Learning points:

  • Even in non-diabetics, hypoglycaemia needs to be excluded in a setting of frequent falls. Insulin- or proinsulin-secreting tumours are potentially curable causes.

  • Whilst investigating spontaneous hypoglycaemia, if plasma insulin concentration is appropriate for the hypoglycaemia, it is prudent to check proinsulin concentrations during the hypoglycaemic episode.

  • Proinsulin cross-reacts variably with C-peptide and insulin assays; the effect is method dependent. In this case, the discrepancy between the insulin and C-peptide concentrations was too great to be accounted for by the faster relative clearance of insulin, raising the suspicion of assay interference. The C-peptide assay in question (Diasorin liaison) has been shown to be 100% cross reactive with proinsulin based on spiking studies with a proinsulin reference preparation.

  • Whilst reported cases of proinsulinoma and 99% of insulinomas are of pancreatic origin, conventional imaging studies (CT, MRI or ultrasound) fail to detect neuroendocrine tumours <1 cm in 50% of cases.

  • The concomitant renal mass identified radiologically proved to be a red herring.

  • In view of the rarity of proinsulinoma, no conclusive association with renal cell carcinoma can be established.

Open access

Chad Bisambar, Andrew Collier, Fraser Duthie and Carron Meney

Summary

A 40-year-old Caucasian female presented with hyperglycaemia, polyuria, polydipsia and weight loss of 6 kg over a 1-month period. There was no personal or family history of malignancy or diabetes mellitus. On examination, she was jaundiced with pale mucous membranes and capillary glucose was 23.1 mmol/L. Initial investigations showed iron deficiency anaemia and obstructive pattern of liver function tests. HbA1c was diagnostic of diabetes mellitus at 79 mmol/mol. Malignancy was suspected and CT chest, abdomen and pelvis showed significant dilatation of intra- and extra-hepatic biliary tree including pancreatic duct, with periampullary 30 mm mass lesion projecting into lumen of duodenum. Enlarged nodes were seen around the superior mesenteric artery. This was confirmed on MRI liver. Fasting gut hormones were normal except for a mildly elevated somatostatin level. Chromogranin A was elevated at 78 pmol/L with normal chromogranin B. Duodenoscopy and biopsy showed possible tubovillous adenoma with low-grade dysplasia, but subsequent endoscopic ultrasound and biopsy revealed a grade 1, well differentiated neuroendocrine tumour. The patient was started on insulin, transfused to Hb >8 g/dL and Whipple’s pancreatico-duodenectomy was undertaken. This showed a well-differentiated neuroendocrine carcinoma arising in duodenum (Grade G1 with Ki67: 0.5%), with areas of chronic pancreatitis and preservation of pancreatic islet cells. There was complete resolution of diabetes post Whipple’s procedure and patient was able to come of insulin treatment. Her last HBA1C was 31 mmol/mol, 4 months post tumour resection.

Learning points:

  • Diabetes mellitus and malignancy can be related.

  • A high index of suspicion is needed when diabetes mellitus presents atypically.

  • Non-functional neuroendocrine tumours can present with diabetes mellitus.

Open access

Daniela Regazzo, Marina Paola Gardiman, Marily Theodoropoulou, Carla Scaroni, Gianluca Occhi and Filippo Ceccato

Summary

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem hereditary cutaneous condition, characterized by multiple hamartomas. In rare cases, pituitary neuroendocrine tumors (PitNETs) have been described in patients with TSC, but the causal relationship between these two diseases is still under debate. TSC is mostly caused by mutations of two tumor suppressor genes, encoding for hamartin (TSC1) and tuberin (TSC2), controlling cell growth and proliferation. Here, we present the case of a 62-year-old Caucasian woman with TSC and a silent gonadotroph PitNET with suprasellar extension, treated with transsphenoidal endoscopic neurosurgery with complete resection. Therapeutic approaches based on mTOR signaling (i.e. everolimus) have been successfully used in patients with TSC and tested in non-functioning PitNET cellular models with promising results. Here, we observed a reduction of cell viability after an in vitro treatment of PitNET’s derived primary cells with everolimus. TSC analysis retrieved no disease-associated variants with the exception of the heterozygous intronic variant c.4006-71C>T found in TSC2: the computational tools predicted a gain of a new splice site with consequent intron retention, not confirmed by an in vitro analysis of patient’s lymphocyte-derived RNA. Further analyses are therefore needed to provide insights on the possible mechanisms involving the hamartin-tuberin complex in the pathogenesis of pituitary adenomas. However, our data further support previous observations of an antiproliferative effect of everolimus on PitNET.

Learning points:

  • Pituitary neuroendocrine tumors (PitNET) in patients with tuberous sclerosis complex (TSC) are rare: only few cases have been reported in literature.

  • Therapeutic approach related to mTOR signaling, such as everolimus, may be used in some patients with PitNETs as well as those with TSC.

  • We reported a woman with both non-secreting PitNET and TSC; PitNET was surgically removed and classified as a silent gonadotroph tumor.

  • Everolimus treatment in PitNET’s-derived primary cells revealed a significant decrease in cell viability.

  • Considering our case and available evidence, it is still unclear whether a PitNET is a part of TSC or just a coincidental tumor.

Open access

Maria P Yavropoulou, Christos Poulios, Christoforos Foroulis, Symeon Tournis, Prodromos Hytiroglou, Kalliopi Kotsa, Isaak Kessisoglou and Pantelis Zebekakis

Summary

Tumor-induced osteomalacia (TIO) is a rare form of hypophosphatemia usually caused by phosphaturic mesenchymal tumors (PMTs); the biologic behavior of PMTs is under investigation. Herein we present a case of TIO with a protracted course over 12 years leading to a fatal outcome. A 39-year-old man presented with weakness in 2004 and was found to have decreased serum phosphorus, phosphaturia and low levels of 1,25-dihydroxyvitamin D3. Four years later he developed a painful left calf mass. The lesion was resected, but recurred causing extreme pain and dysfunction. Radiological examination showed a large cluster of soft tissue tumors affecting all the muscle compartments of the calf and a smaller lesion inside the metaphysis of the tibia. Above-knee amputation was performed. Histological examination of all lesions showed a cellular spindle cell neoplasm with variously sized vessels, wide vessel-like spaces and scattered deposits of calcified extracellular material. The tumor infiltrated skeletal muscles, subcutaneous fat and the proximal end of the fibula. The tibial lesion had identical histology. Three years after the amputation the patient presented with cough and dyspnea. Radiological examination, followed by an open biopsy, showed that there were multiple metastatic nodules of PMTs in both lungs. Shortly after the diagnosis the patient died. This case illustrates that even benign cases of PMTs may lead to a fatal outcome and the classification of PMTs into benign and malignant should be reassessed in order to correspond to its biological behavior.

Learning points:

  • PMTs, aside from having locally aggressive behavior, may metastasize and cause death

  • PMTs may behave aggressively despite ‘benign’ histological findings

  • Accurate diagnosis of tumor-induced osteomalacia and patient management require a multidisciplinary approach

Open access

Carlos Tavares Bello, Patricia Cipriano, Vanessa Henriques, João Sequeira Duarte and Conceição Canas Marques

Summary

Granular cell tumours (GCT) are rare, slow-growing, benign neoplasms that are usually located in the head and neck. They are more frequent in the female gender and typically have an asymptomatic clinical course, being diagnosed only at autopsy. Symptomatic GCT of the neurohypophysis are exceedingly rare, being less than 70 cases described so far. The authors report on a case of a 28-year-old male that presented to the Endocrinology clinic with clinical and biochemical evidence of hypogonadism. He also reported minor headaches without any major visual symptoms. Further laboratory tests confirmed hypopituitarism (hypogonadotrophic hypogonadism, central hypothyroidism and hypocortisolism) and central nervous system imaging revealed a pituitary macroadenoma. The patient underwent transcranial pituitary adenoma resection and the pathology report described a GCT of the neurohypophysis with low mitotic index. The reported case is noteworthy for the rarity of the clinicopathological entity.

Learning points:

  • Symptomatic GCTs are rare CNS tumours whose cell of origin is not well defined that usually give rise to visual symptoms, headache and endocrine dysfunction.

  • Imaging is quite unspecific and diagnosis is difficult to establish preoperatively.

  • Surgical excision is challenging due to lesion’s high vascularity and propensity to adhere to adjacent structures.

  • The reported case is noteworthy for the rarity of the clinicopathological entity.

Open access

Joseph A Chorny, John J Orrego and José Manuel Cameselle-Teijeiro

Summary

Most medullary thyroid carcinomas (MTCs) are low grade and produce calcitonin. There are some calcitonin-negative MTCs that produce only calcitonin gene-related peptide (CGRP). Rarely, MTCs are negative for calcitonin and CGRP peptides, but contain their corresponding mRNAs. Primary thyroid neuroendocrine neoplasms other than MTCs are extremely rare. We describe a primary high-grade neuroendocrine carcinoma that was negative for CGRP and calcitonin at both the protein and mRNA levels. A 42-year-old woman presented with a rapidly enlarging thyroid mass replacing most of the left lobe and isthmus. A computed tomography-guided core-needle biopsy was performed. The tumor was composed of sheets of small-to-medium sized epithelial cells. The cells were immunoreactive for pancytokeratin, synaptophysin, CD56 and thyroid transcription factor-1, but negative for CK7, CK20, CD45, CD99, ERG, chromogranin A, thyroglobulin, calcitonin, CGRP and carcinoembryonic antigen. The Ki-67 proliferation index was ~90%. In situ hybridization was negative for calcitonin mRNA. The patient was initially diagnosed as having a small cell carcinoma. She was treated with cisplatin and etoposide (VP16), followed by radiation therapy. Given the excellent clinical course, the tumor was reviewed and reclassified as a high-grade neuroendocrine carcinoma (non-small-cell type). Heretofore, only a few other similar high-grade neuroendocrine tumors with negative markers of C-cell derivation have been reported. In our case, the patient is cancer free five years after diagnosis, but in the other cases, the outcome was poor.

Learning points:

  • There are neuroendocrine carcinomas of the thyroid that do not produce calcitonin or calcitonin gene-related peptide.

  • This category of calcitonin-negative neuroendocrine carcinomas is heterogeneous, consisting of low- and high-grade tumors.

  • The high-grade neuroendocrine carcinomas of the thyroid are rare and generally have a poor prognosis. They are divided into small cell and non-small cell or large cell types.

Open access

Tiago Nunes da Silva, M L F van Velthuysen, Casper H J van Eijck, Jaap J Teunissen, J Hofland and Wouter W de Herder

Summary

Non-functional pancreatic neuroendocrine tumours (NETs) can present with advanced local or distant (metastatic) disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT) using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate) for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

Learning points:

  • PRRT with 177Lu-octreotate can be considered a useful therapy for symptomatic somatostatin receptor-positive pancreatic NET.

  • The clinical benefits of PRRT with 177Lu-octreotate can be seen in the first months while tumour reduction can be seen up to a year after treatment.

  • PRRT with 177Lu-octreotate was clinically well tolerated and did not interfere with the subsequent surgical procedure.

  • PRRT with 177Lu-octreotate can result in significant tumour reduction and may improve surgical outcomes. As such, this therapy can be considered as a neoadjuvant therapy.

Open access

Raluca Maria Furnica, Julie Lelotte, Thierry Duprez, Dominique Maiter and Orsalia Alexopoulou

Summary

A 26-year-old woman presented with severe postpartum headaches. Magnetic resonance imaging (MRI) revealed a symmetric, heterogeneous enlargement of the pituitary gland. Three months later, she developed central diabetes insipidus. A diagnosis of postpartum hypophysitis was suspected and corticosteroids were prescribed. Six months later, the pituitary mass showed further enlargement and characteristics of a necrotic abscess with a peripheral shell and infiltration of the hypothalamus. Transsphenoidal surgery was performed, disclosing a pus-filled cavity which was drained. No bacterial growth was observed, except a single positive blood culture for Staphylococcus aureus, considered at that time as a potential contaminant. A short antibiotic course was, however, administered together with hormonal substitution for panhypopituitarism. Four months after her discharge, severe headaches recurred. Pituitary MRI was suggestive of a persistent inflammatory mass of the sellar region. She underwent a new transsphenoidal resection of a residual abscess. At that time, the sellar aspiration fluid was positive for Staphylococcus aureus and she was treated with antibiotics for 6 weeks, after which she had complete resolution of her infection. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.

Learning points:

  • The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.

  • In a significant proportion of cases no pathogenic organism can be isolated.

  • A close follow-up is necessary given the risk of recurrence and the high rate of postoperative pituitary deficiencies.