Case Report: Identification of Potential Prognosis-Related TP53 Mutation and BCL6-LPP Fusion in Primary Pituitary Lymphoma by Next Generation Sequencing: Two Cases

BackgroundPrimary pituitary lymphoma (PPL) is an extremely rare disease with poor prognosis. Although PPL has been shown to be different from classical primary central nervous system lymphoma because of the embryological origin of structures, individual and precise treatment of PPL remains unknown.MethodsA 61-year-old man and a 65-year-old woman both diagnosed with primary pituitary diffuse large B cell lymphoma underwent genetic analysis of cerebrospinal fluid and tumor tissue by next generation sequencing.ResultsIn the first case, partial remission was achieved following R²-MTX chemotherapy. In the other case with TP53 mutation and BCL6-LPP fusion, disease progressed although different chemotherapy regimens were given.ConclusionThe gene mutation of TP53 and BCL6 may be identified as a marker responsible for prognostic difference in patients with PPL. Genetic analysis may provide a novel approach for precise management and prognosis prediction.

HIV and the Pituitary Gland: Clinical and Biochemical Presentations

Human immunodeficiency virus (HIV) can have profound impact on the function of the pituitary gland. We have performed an electronic literature search using the following database: PubMed, Medline, Scopus, and Google Scholar. These databases were searched using the keywords HIV, pituitary glands, cancer, pituitary apoplexy, and infertility. HIV can cause hypopituitarism and also can lead to diabetes insipidus. The impact can be slow and insidious, and diagnosis depends on high index of clinical suspicion. The effect on anterior pituitary gland can be associated with growth hormone deficiency, hypothyroidism, adrenal insufficiency, premature menopause, erectile dysfunction, and infertility. HIV can cause pituitary apoplexy, and this should be treated as an endocrine emergency. Importantly, HIV can be associated with pituitary lymphoma and pituitary cancer. Therefore, joined management between HIV physicians, clinical biochemists and endocrinologists may help in establishing pituitary dysfunction.

Primary Pituitary Lymphoma in Immunocompetent Patients: A Report on Two Case Studies and the Review of Literature

Primary pituitary lymphoma (PPL) represents an extremely rare entity. Here, we have reported two recently identified cases of immunocompetent PPL having diffuse large B-cell lymphoma by surgical biopsy. Both patients had hypopituitarism, with one patient developing right ptosis. In both patients, MRI and FDG-PET/CT depicted sellar mass that extended into the cavernous sinus with the right sphenoid also present in one of the patients. No systemic disease was found in these two patients. Surprisingly, we found that both patients had infiltrative lesions in sphenoid sinus mucosa pathologically, but the sphenoid bones that composed the sellar base were visually intact during the biopsy procedure. Chemotherapy was administered to both patients, where one patient achieved remission at the recent follow-up, whereas the other one did not respond to the treatment. The diagnosis of PPL is usually difficult if solely dependent on history, clinical presentation, biochemical indexes, and radiographic findings. We have also updated and reviewed the epidemiologic features, clinical presentations, pathological characteristics, potential mechanisms, therapeutic orientation, and prognostic advances of PPL. A total of 40 cases (including ours and four pediatric patients), histologically diagnosed, were analyzed in terms of clinical presentation, endocrine abnormality, radiological features, pathology, treatment, and follow-up. Hypopituitarism and headache were the most common presentation of PPL, while diabetes insipidus was reported in 13 patients (43.3%). B cell lymphoma was the most common type of pathology, followed by T-cell and NK/T cell. PPL was more invasive in nature at the suprasellar region (72.5%), cavernous sinus (52.5%), and sphenoidal sinus (27.5%) in 29, 21, and 11 patients, respectively. Pediatric patients with PPL seem to be different compared to their adult counterparts in terms of pathogenesis, clinical presentation, and radiological features. The management of PPL usually follows the treatment protocols for PCNSL but has a poor prognosis compared to the pituitary involvement of systemic lymphoma.

PRIMARY PITUITARY LYMPHOMA AS RARE CAUSE OF A PITUITARY MASS AND HYPOPITUITARISM IN ADULTHOOD

Objective: Differential diagnosis of nonadenomatous sellar masses causing hypopituitarism is still a challenge. Among these masses, growing evidence has demonstrated that primary pituitary lymphoma is a specific and emerging entity. The aim of our study was to describe our experience with a case of primary pituitary lymphoma and to perform a review of the available literature. Methods: We searched relevant databases up to March 2020, identifying 36 suitable articles basing on inclusion criteria (primary pituitary lymphoma in adult immunocompetent subjects). Overall, 43 cases were included in the review, adding a new case diagnosed and treated in our hospital. Epidemiologic data, clinical presentation, hormonal status, radiologic findings, pathology, treatment, and outcome were extracted. Results: Mean age at diagnosis was 58.9 years, without gender difference. Symptoms related to mass were common (52.3%), in particular cranial nerve palsy (70.5%), headache (56.8%), and alteration in visual field (40.9%). Impaired hormonal status was detected in 89.7% of patients; of them, 58.9% presented with anterior pituitary failure (partial or total), while 25.6% presented with panhypopituitarism. Overall, diabetes insipidus was present in 30.8% and hyperprolactinemia in 41.0% of patients. The majority of patients presented a radiologically invasive mass in the suprasellar region and cavernous sinus (65.9% and 40.9%, respectively) and histologic diagnosis of diffuse B-cell lymphoma (54.5%). Conclusion: The differential diagnosis of sellar and parasellar masses causing hypopituitarism should include primary pituitary lymphoma, even in absence of systemic symptoms or posterior pituitary dysfunction. The disease has a heterogeneous pattern, so a collaboration between endocrinologists, neuroradiologists, neurosurgeons, and hematologists is desirable. Abbreviations: ACTH = adrenocorticotropic hormone; DI = diabetes insipidus; FSH = follicle-stimulating hormone; GH = growth hormone; GHD = growth hormone deficiency; IGF-I = insulin-like growth factor-I; MRI = magnetic resonance imaging; PRL = prolactin; TSH = thyroid-stimulating hormone

MON-237 Primary Pituitary Lymphoma - an Unusual Guest in the Sella!

Background Primary Pituitary Lymphoma (PPL) is a rare differential diagnosis for a sellar / suprasellar lesion. Less than 40 cases have been reported. Case presentation A 75-year old Chinese lady with known subclinical hypothyroidism presented with 3-day history of dull frontal headache, giddiness and diplopia. Incomplete left cranial nerve (CN) III palsy was noted with no other neurological deficit or hemodynamic instability. MRI brain and pituitary showed a T1- and T2 isointense, 2.0 x 1.1 x 1.3 cm enhancing mass arising from the left sellar region, extending to the left sphenoid and cavernous sinuses, displacing the pituitary stalk towards the right, with no optic chiasm compression. There was no imaging evidence of apoplexy. Evaluation of anterior pituitary hormones revealed hypocortisolism (peak cortisol post 1mcg Synacthen 344 nmol/L, ACTH 3.5 ng/L [10 - 60]), subclinical hypothyroidism (free T4 9.6 pmol/L [8.8 - 14.4], TSH 7.19 mU/L [0.65 - 3.70]), normal prolactin 7.4 ug/L [5.0-27.7], mildly elevated IGF-1 193.7 mcg/L [67.0 - 189.0] with normal GH 1.0 ng/ml, and elevated FSH appropriate for menopause. Glucocorticoid replacement was started. Though the clinical presentation was not typical of a pituitary macroadenoma, in view of symptomatic improvement and neurological stability, she was conservatively managed with plans for early repeat imaging outpatient. Patient was readmitted 1 month later for headache and decreased left-sided visual acuity. A complete CN III palsy, and new CN II, IV and VI deficits were noted (orbital apex syndrome). Repeat MRI showed increase in the size of the sellar lesion to 2.6 x 2.1 x 1.3 cm, surrounding the optic nerve and with left cavernous and sphenoid sinus invasion. Again, there was no suggestion of apoplexy. Biopsy of the lesion was performed, and histology was consistent with Diffuse Large B-cell Lymphoma and Grade 3A Follicular Lymphoma with high proliferative index (Ki67 70%). Immunohistochemistry excluded carcinoma, meningioma and pituitary tumor. PET-CT and bone marrow aspirate confirmed the diagnosis of PPL without metastasis. After 3 cycles of chemotherapy (Methotrexate, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), significant decrease in the size of the lesion was noted on repeat MRI. Only mild asymmetric soft tissue thickening remained noticeable over the left sella and cavernous sinus. Cranial nerve deficits had since completely resolved. Glucocorticoid replacement was continued in the meantime while awaiting the completion of chemotherapy. Conclusion PPL may present in a similar manner as pituitary apoplexy. Absence of typical imaging characteristics of apoplexy in patients with rapid symptom progression and CN involvement should alert clinicians to consider alternative diagnosis including aggressive neoplastic, inflammatory and infective lesions.

Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental?

BACKGROUND AND IMPORTANCE: Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis. CLINICAL PRESENTATION: A 74-year-old man presented with a concomitant primary pituitary lymphoma (diffuse large B-cell non-Hodgkin's lymphoma; DLBCL) and follicle-stimulating hormone (FSH)-adenoma diagnosed histologically after clinical features of apoplexy prompted urgent surgical decompression and resection. Strong immunoreactivity for FSH by the lymphoma was evident. Full-body workup demonstrated no other source for the lymphoma. He subsequently underwent 4 cycles of chemotherapy and has been in remission for over 32 months. His ophthalmoplegia at presentation persisted with no further deficits. CONCLUSIONS: Four cases of collision tumors of primary pituitary lymphoma and adenoma have previously been reported. This case represents the first combination of an FSH-adenoma and a DLBCL in the literature. Prompt involvement of the hematology-oncology team contributed to the good outcome seen in this case. The putative role played by pituitary hormones in tumorigenesis is reviewed in this case report. The association is either a chance occurrence or due to the induction of lymphoma cell proliferation by the binding of FSH produced by the adenoma to the FSH receptors on the lymphoma cells.

Malignant Lymphoma in the Parasellar Region

The entity of pituitary (sellar or parasellar) lymphoma includes primary pituitary lymphoma (PPL) and secondary pituitary lymphoma (SPL). The latter has an involvement of systemic lymphoma. Both of these lymphomas are extremely rare. We describe a patient with SPL showing a good prognosis. A 78-year-old woman presented with diplopia, left ptosis, and back pain. Magnetic resonance (MR) imaging revealed a parasellar mass lesion extending to the upper clivus and another mass lesion with compression fracture of the Th3 vertebral body. Transsphenoidal exploration was performed, and it showed diffuse large B-cell lymphoma. Based on the positive tumor cells in the following bone marrow aspiration and hepatosplenomegaly in computed tomography (CT) findings, this patient was diagnosed as having a pituitary involvement of systemic lymphoma. After chemotherapy, she achieved complete remission for 4 years. The entity of pituitary lymphoma is extremely rare. Nineteen cases of PPL and 16 cases of SPL have been reported. Generally, clinical and radiological diagnosis was difficult because there are no specific findings. Therefore, biopsy was necessary in all of the cases. T2 hypointensity of a lesion in MR imaging in addition to an elevated serum level of soluble interleukin-2 receptor (sIL-2R) in a patient with a sellar lesion can be useful clues for the differential diagnosis of this rare disease.