Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report

This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma.     

Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma

Stereotactic radiosurgery is being used with increased frequency in the treatment of residual or recurrent pituitary adenomas. The major risk associated with radiosurgical treatment of residual or recurrent pituitary tumor adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors describe a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual pituitary adenoma within the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and a fat and fascia graft is interposed between the normal pituitary gland and the residual tumor in the cavernous sinus. The residual tumor may then be treated with stereotactic radiosurgery. The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery and reduces the radiation to the normal pituitary gland. An illustrative case of a young female with recurrent acromegaly and a pituitary adenoma invading the cavernous sinus is described.     

A case of oncocytic adenoma of the pituitary gland with galactorrhea and hyperprolactinemia]

A tumor of hypophysis, with suprasellar expansion, was removed surgically in a 68 years old woman with panhypopituitarism and galactorrhea. Light and electron microscopy studies have shown an oncocytoma. One year after pituitary ablation and cobaltherapy, the patient had normal pituitary functions and galactorrhea had disappeared. Since the prolactin cells were outside the adenoma and the prolactin secretion became normal after surgery, we can assume that galactorrhea was presumably due to the compression of the pituitary stalk by oncocytoma.     

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.     

Primary central nervous system lymphoma mimicking pituitary apoplexy: case report

Lymphoma involving the pituitary gland is very rare and usually results from metastatic spread of systemic lymphoma. We present a case of primary central nervous system (CNS) large B cell lymphoma that manifested as pituitary apoplexy. A 45-year-old woman presented with headache, and then rapidly developed a third nerve palsy and bitemporal hemianopsia. Imaging suggested a pituitary macroadenoma, with spontaneous necrosis, extending into the suprasellar region, compressing the optic chiasm and invading the right cavernous sinus. The patient underwent transsphenoidal resection which revealed a vascular, firm tumor. An aggressive decompression of the optic chiasm was performed with complete resolution of both visual fields and third nerve palsy. Final pathology showed B cell lymphoma. Systemic work-up including bone marrow aspiration and CSF studies showed no other foci of lymphoma, and the patient was HIV-negative. Chemotherapy with methotrexate, vincristine, procarbazine, and dexamethasone was administered for primary CNS lymphoma. This is an uncommon diagnosis of which the clinician should be aware in order to tailor surgical intervention and provide early institution of proper therapy.     

Bromocriptine-induced regression of a suprasellar extending prolactinoma during pregnancy

A 21-year-old amenorrheic woman with hyperprolactinemia had rapid pituitary tumor enlargment during a bromocriptine-induced pregnancy. Before treatment the sella turcica was normal. In the 31st week of pregnancy she developed bitemporal hemianopsia and markedly decreased visual acuity. Computerized tomography showed a pituitary adenoma with suprasellar extension. Reinstitution of bromocriptine therapy resulted in rapid recovery of normal vision and radiologically verified tumor regression. Pregnancy continued to term and a healthy child was born. If pituitary tumor complications should occur during pregnancy, reinstitution of bromocriptine is the primary treatment of choice.     

Thyrotropin-secreting pituitary adenoma presenting as hypokalemic periodic paralysis

Thyrotropin (TSH)-secreting pituitary adenoma presenting with hypokalemic periodic paralysis is extraordinarily rare and may be misdiagnosed. We describe a 44-year-old man who suffered from acute muscle weakness and inability to ambulate upon awakening in the morning. Physical examination showed hypertension, tachycardia, and symmetrical flaccid paralysis of all extremities. The major biochemical abnormality was hypokalemia (K+, 2.0 mmol/L) with low urine K+ excretion. A thyroid function study revealed elevated thyroid hormone levels and inappropriately high TSH concentrations (2.10 microU/mL). Brain magnetic resonance imaging delineated a pituitary tumor with suprasellar extension. After trans-sphenoidal removal of tumor, he became clinically and biochemically euthyroid without any further attack of paralysis. Pathological findings confirmed a TSH-secreting adenoma with exclusive TSH immunostaining. TSH-secreting pituitary adenoma must be kept in the differential diagnosis in any thyrotoxic periodic paralysis patients with detectable TSH levels to avoid delaying diagnosis and management.     

Granulomatous hypophysitis associated with Takayasu's disease

We report a case of Takayasu's disease, presenting with symptoms of fever, anaemia, elevated erythrocyte sedimentation rate, anterior pituitary failure and mild diabetes insipidus. A pituitary mass with suprasellar extension mimicking a pituitary adenoma was found, and histological examination revealed granulomatous hypophysitis. The diagnosis of Takayasu's disease was established after the development of a multiple arterial occlusive disease. We suggest that Takayasu's disease should be considered in the differential diagnosis of granulomatous hypophysitis of unknown origin.     

Corticotroph cell adenoma without typical manifestations of Cushing's disease presenting with cavernous sinus syndrome following pituitary apoplexy

This report presents a unique case of corticotroph cell adenoma in a 30-year-old man without acromegaly or features typical of Cushing's disease, who developed cavernous sinus syndrome following pituitary apoplexy. Magnetic resonance imaging revealed a large intrasellar/suprasellar mass with pituitary hemorrhage and extension of a hematoma to the anterior base of the skull. Urgent transnasal pituitary surgery revealed an acidophilic pituitary adenoma, with immunoreactivity for ACTH and GH and expression of proopiomelanocortin (POMC) and GH messenger ribonucleic acid (mRNA) demonstrated by in situ hybridization. To our knowledge, a silent corticotroph cell adenoma with GH production has never been reported. This type of adenoma may potentially enlarge and develop tumoral hemorrhage because it is free of endocrinological symptoms.     

Primary hypothyroidism mimicking pituitary adenoma

The case history is presented of a woman with secondary amenorrhoea, mild hyperprolactinaemia and pituitary enlargement with suprasellar extension, mimicking a pituitary adenoma. It appeared that she had primary hypothyroidism. After L-thyroxine treatment, all abnormalities disappeared. The literature on the combination of primary hypothyroidism, hyperprolactinaemia and pituitary enlargement is reviewed and the pathophysiology is discussed. It is concluded that determination of thyrotropin is essential in all patients with pituitary enlargement and hyperprolactinaemia.     

Pituitary lymphoma presenting as fever of unknown origin

An 86-yr-old woman presented with fever of unknown origin. When laboratory evaluation revealed partial hypopituitarism, a magnetic resonance imaging scan of the head was performed and revealed a sellar mass consistent with a pituitary adenoma. Only after other possible etiologies for fever were excluded did she undergo transsphenoidal resection of the sellar mass, which proved to be a B-cell lymphoma. Primary central nervous system lymphoma of the pituitary region is a rare cause of a sellar mass, and this is the first reported case of pituitary lymphoma whose presenting manifestation was fever of unknown origin. Several disease processes can manifest themselves as fever and a sellar mass, including lymphomas. In our case, only surgical biopsy could make a diagnosis and distinguish this process from the more common pituitary adenoma.     

Intra- and Suprasellar Colloid Cysts

During the past 11 years 69 patients underwent transsphenoidal surgery for symptomatic intra- and suprasellar non-neoplastic cysts in our department. Eighteen of them harbored intra- and suprasellar colloid cysts. The most frequent presenting symptoms were oligomenorrhea, galactorrhea, and headaches. One patient presented with polydipsia. One male patient complained about mild hypogonadism and oligospermia. Two male patients presented with symptoms of panhypopituitarism. Endocrine assessment revealed hyperprolactinaemia in 72% of the female patients. Hypogonadism was found in 72%. Panhypopituitarism was found in two cases. During transsphenoidal surgery, a circumscribed collection of colloid material was removed in each case. Additional tumorous tissue was encountered in three cases that harbored a concomitant pituitary adenoma. Biopsies confirmed the surrounding tissue to be normal pituitary tissue. Postoperatively, regular menstrual cycles were found in 82% of the female patients with oligomenorrhea and headaches improved in 80%. Serum prolactin levels were restored in 92%, galactorrhea ceased in 89%. Only in one case deterioration of pituitary function occurred (diabetes insipidus). Symptomatic SIADH occurred in another one. There were no other postoperative complications. We conclude, that transsphenoidal surgery is a safe therapy for treating symptomatic intra- and suprasellar colloid cysts. Surgery is mainly indicated for female patients in childbearing age to restore fertility and to prevent further deterioration of pituitary function. The differential diagnosis is often unclear preoperatively, but a non-enhancing mass on MRI between anterior and posterior lobe may suggest the presence of an intra- and suprasellar colloid cyst.     

Long term outcome following repeat transsphenoidal surgery for recurrent endocrine-inactive pituitary adenomas

It is widely accepted that the standard first-line treatment for most endocrine inactive pituitary macroadenomas (EIA) is surgery, usually via a transsphenoidal approach. What is less clear is what approach to take when these tumors recur, especially when this recurrence involves areas which are difficult to surgically remove tumor from, such as the suprasellar region or cavernous sinuses. We present long term follow-up for a series of 81 patients who underwent repeat surgery for recurrent non-secreting pituitary adenomas. We analyzed data collected from all adult patients undergoing their second microsurgical transsphenoidal resection of a histologically proven endocrine-inactive pituitary adenoma at the University of California at San Francisco between January 1970 and March 2001. Data for these patients were collected by review of medical records, mail, and/or telephone interviews. Visual function, anterior pituitary function, and tumor control rates were analyzed for the series. Records were available for a total of 81 recurrent EIA patients. The median time between their initial and repeat operations was 4.1 years. The mean tumor size was 2.2 ± 0.2 cm. A total of 35/81 patients had greater than 5 years of follow-up. A total of 24/81 patients had greater than 10 years of follow-up. Over one half of these patients presented with visual disturbance, and we found that 39% of these patients experienced improved vision with a second surgery. More importantly, no one with normal vision suffered any appreciable decline in vision. Approximately, 35% of patients with pre-operative anterior pituitary dysfunction recovered function after surgery in our series; and no patient’s function worsened. A total of 4/52 (8%) patients with greater than 2 years of post-op follow-up experienced a clinically meaningful tumor recurrence requiring additional treatment. Our data suggest that when performed by experienced transsphenoidal surgeons, durable tumor control can be obtained in these frequently locally aggressive tumors with acceptable rates of post-operative morbidity.     

Granulomatous hypophysitis with meningitis and hypopituitarism.

We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis.     

Coexistence of TSH-secreting pituitary adenoma and autoimmune hypothyroidism

OBJECTIVE: TSH-secreting pituitary adenomas account for about 1-2% of all pituitary adenomas. Their diagnosis may be very difficult when coexistence of other diseases masquerades the clinical and biochemical manifestations of TSH-hypersecretion. CLINICAL PRESENTATION: A 41-yr-old female patient, weighing 56 kg, was referred for evaluation of an intra- and suprasellar mass causing menstrual irregularities. Eight yr before, the patient had been given a diagnosis of subclinical autoimmune hypothyroidism because of slightly elevated TSH levels and low-normal free T4 (FT4). Menses were normal. Despite increasing doses of levo-T4 (L-T4; up to 125 microg/day), TSH levels remained elevated and the patient developed mild symptoms of hyperthyroidism. After 7 yr, the menstrual cycle ceased. Gonadotropins were normal, whereas PRL level was elevated at 70 microg/l and magnetic resonance imaging (MRI) of the hypothalamic- pituitary region revealed a pituitary lesion with slight suprasellar extension. The tumor was surgically removed and histological examinations revealed a pituitary adenoma strongly positive for TSH. Three months after surgery the patient was well while receiving L-T4 75 microg/day and normal menses had resumed. MRI of the hypothalamic-pituitary region showed no evidence of residual tumor. At the last follow-up, 16 months after surgery, serum TSH, free T3 (FT3), and FT4 levels were normal. CONCLUSIONS: Coexistence of autoimmune hypothyroidism and TSH-secreting pituitary adenoma may cause further delays in the diagnosis of the latter. In patients with autoimmune hypothyroidism, one should be aware of the possible presence of a TSH-secreting pituitary adenoma when TSH levels do not adequately suppress in the face of high doses of L-T4 replacement therapy and elevated serum thyroid hormone levels.     

A non-functioning pituitary adenoma initially mimicking a microprolactinoma: The case for long-term follow-up of patients with mild hyperprolactinemia?

OBJECTIVE: A correct differential diagnosis of patients with mild hyperprolactinemia is essential to select the most appropriate treatment modality. CLINICAL PRESENTATION: A 50-yr-old woman presented to our Department for evaluation of an intra- and suprasellar mass causing progressive visual defect. Mild hyperprolactinemia causing menstrual irregularities was diagnosed in February 1989. In 1992, serum PRL levels ranged from 50 to 70 microg/l and magnetic resonance imaging (MRI) of the hypothalamic-pituitary region showed the presence of a 7 mm microadenoma. Bromocriptine therapy resulted in normalization of PRL levels and menstrual cycle, while a repeat MRI showed no change. Menses stopped in March 1998, when the patient was 46 yr old. Subsequently, the patient complained of worsening headaches and, starting from July 2001, visual disturbances. In March 2002, MRI showed a large pituitary tumor, measuring 40x37x28 mm. In May 2002, the patient was operated through the transsphenoidal approach with apparent total tumor removal. Histological examination confirmed a pituitary adenoma that stained negative for all pituitary hormones. Four months after surgery, the patient reported an improvement of visual function. MRI of the hypothalamic-pituitary region, performed 4, 13 and 25 months after surgery, showed a partially empty sella with no evidence of residual tumor. CONCLUSIONS: This case suggests that, to exclude the alternative diagnosis of nonfunctioning pituitary adenoma or another mass lesion of the hypothalamic-pituitary region, repeat neuroimaging studies during long-term follow-up may be advisable in patients with presumed microprolactinoma who did not show reduction of the tumor during dopaminergic therapy.     

Successful Management of a Pregnant Woman with a TSH Secreting Pituitary Adenoma with Surgical and Medical Therapy

We described a 39-yr-old asian female who was initially diagnosed with prolactinoma and presented with increase nervousness and weight loss. Laboratory evaluation revealed an inappropriately normal TSH level with elevated free T4, total T3, alpha-subunit and prolactin level. The alpha-subunit/TSH molar ratio was 4. MRI showed a macroadenoma extending to the suprasellar cistern. Treatment was begun with propylthiouracil and bromocriptine. After 5 months of therapy, she became pregnant. At 27 weeks of gestation, she developed headache and decreased visual acuity in her left eye. MRI showed a slightly increase in tumor size compressing the optic chaiasm. Transphenoid macroadenectomy was performed with immediate relief of the visual field abnormality. At 39 weeks gestation a baby with no malformations was delivered. This is the second case report of TSH secreting pituitary adenoma which was exarcerbated during pregnancy. In contrast to the first case, our case was managed with both surgical and medical approach. The judicious use of both medical and surgical therapy can result in a successful outcome to mother and fetus in a patient with TSH secreting pituitary adenoma.     

Sellar Neuroblastoma Mimicking Pituitary Adenoma

Objective and importance: Primary intracranial neuroblastomas are rare. They generally arise in the supratentorial parenchyma or paraventricular region. Even more rare are primary sellar neuroblastomas. We present a neuroblastoma that arose in the sellar region and mimicked a non-functioning pituitary adenoma. Clinical presentation: This 33-year-old man presented with bitemporal hemianopsia. MRI showed a sellar mass with suprasellar extension mimicking a pituitary adenoma. Intervention: Because of tumor recurrence and dissemination to the cervical region, he underwent 6 operations and radiosurgery. Detailed histologic examination confirmed the diagnosis of neuroblastoma. Postoperative conventional radiotherapy was effective in reducing the size of the tumor. Conclusion: Neuroblastoma should be considered in the differential diagnosis of patients with sellar lesions.