Primary Hypothalamic Lymphoma in an Adult Male: A Case Report and Literature Review.
A 50-year-old male reported with complaints of memory disturbances and irritability of three weeks duration. His family had noticed that his short-term memory was grossly impaired. There was no associated history of headache, vomiting, fever, seizures, urine incontinence, or gait disturbance. His medical history was insignificant. On examination, he was irritable and confused. Assessment of his higher mental functions could not be done. There was no cranial nerve involvement or motor deficit.
Complete blood, cerebrospinal fluid (CSF), and radiological evaluation were performed. Serum electrolytes revealed hypernatremia (sodium 155 mEq/dL), which was corrected. His remaining electrolytes, blood sugar, kidney, and liver function tests were normal. His hemoglobin level was 9.6 g/dL, and leucocyte count was 7600/[mm.sup.3]. Lumbar CSF had 56 mg/dL proteins, 49 mg/dL sugar, and 8% lymphocytes. Serology test for tuberculosis with the polymerase chain reaction method and adenosine deaminase (ADA) activity were negative. Computed tomography (CT) scan of the chest, abdomen, and pelvis did not reveal any abnormality. His screening for anterior and posterior pituitary hormones was normal. Before subjecting the patient to a surgical procedure, a routine HIV-screening test was done, which was negative. Brain imaging revealed an enhancing suprasellar mass with areas of restricted diffusion within the mass [Figure 1 and 2].
A stereotactic tissue biopsy from the lesion showed features of large B-cell lymphoma. Histopathological examination showed a uniform population of large lymphoid cells. The cells had scanty cytoplasm and were arranged in a typical angiocentric pattern. Immunohistochemistry showed the tumor cells positive for leukocyte common antigen (LCA), and B-cell markers CD20 and CD19 [Figure 3]. Based on these histological and immunohistochemical features, a diagnosis of a diffuse primary large B-cell lymphoma was made. He was referred to a medical oncologist for further management. The patient was given six cycles of an intravenous high-dose methotrexate-based regimen (methotrexate 3.5 gm/[m.sup.2], vincristine 2 mg/[m.sup.2], procarbazine 100 mg/[m.sup.2], and cytarabine 100 mg/[m.sup.2] (post-radiation)) followed by consolidation therapy of one cycle of whole-brain radiotherapy (40 Gy to the whole brain, 2 Gy/day x 20 days). The patient was put on methylprednisolone 60 mg/day to reduce cerebral edema. After commencement of treatment and as edema subsided there was a significant improvement in his cognition and headache. At three-month follow-up, he was doing well and repeat scans showed noticeable regression of the lesion.
Primary CNS lymphoma is a rare malignant primary CNS neoplasm comprising 0.85-2.0% of all primary brain tumors and 0.2-2.0% of malignant lymphomas. (1) The incidence of primary CNS lymphomas is increasing relative to gliomas and meningiomas probably due to increasing number of transplant and patients with acquired immunodeficiency syndrome. (4) Primary CNS lymphomas usually present with signs of focal mass lesion in 61% of patients, neuropsychiatric signs in 43%, features of raised intracranial pressure in 33%, and seizures in 14% of patients. (4,5) Seizures are less common than with other types of brain tumors probably because primary CNS lymphoma involves predominantly subcortical white matter rather than epileptogenic gray matter. The lesion is commonly located in the periventricular region, especially around the lateral ventricles. Other sites involved are the thalamus, basal ganglia, corpus callosum, cerebellum, and spine. CNS lymphoma presenting as a unique, solitary mass located in the hypothalamic, and/or third ventricular region is very unusual. Only a few cases have been reported [Table 1]. (6-23)
Our patient presented with memory disturbances and irritability because of the hypothalamic involvement. There were no raised intracranial pressure symptoms. Other lesions that involve the hypothalamus and third ventricular region include pituitary macroadenomas, craniopharyngiomas, meningiomas, metastases, optic and hypothalamic pilocytic astrocytomas, Rathke cleft cysts, hamartomas of the tuber cinereum, chordoid glioma, and granulomatous diseases such as sarcoid, tuberculosis, and eosinophilic granuloma. (13)
Pomper et al, (3) reported that chordoid gliomas located in the region of the hypothalamus and anterior third ventricle are ovoid in shape and well circumscribed. They also reported that vasogenic edema seen in these gliomas might help to distinguish them from meningiomas. (3) As tuberculosis is a very common entity in Asia, it was considered among the differential diagnosis in our patient. However, our patient's CSF was negative for markers of tuberculosis. Metastasis from a primary tumor can also sometimes involve the hypothalamic region, however, in our patient, preliminary screening for primary tumor by CT scan of the chest, abdomen, and pelvis was negative. The possibility of neurosarcoidosis, which often involves the meninges, cranial nerves, hypothalamus, and infundibular stalk should also be considered in such type of settings as it occasionally presents as a focal extra-axial or parenchymal mass. (24,25)
CT scan shows lymphomas to be iso- to hyperdense lesions. This feature is because of their hypercellularity. Also, lymphomas are homogenously enhancing lesions. Diffusion-weighted magnetic resonance imaging (MRI) shows restricted diffusion because of the hypercellularity of the lesion.
The most common histopathological subtypes seen in the CNS are large B-cell lymphoma. The cells are LCA positive (a leukocyte marker) and CD20 positive. Treatment options for primary CNS lymphoma (PCNSL) include corticosteroids, chemotherapy, and radiation. Resection of PCNSL is not a viable treatment option except in those with brain herniation due to mass effect. (25,26) Although PCNSL is a potentially curable brain tumor in an immunocompetent patient; the best treatment strategy has yet to be defined. Current treatment options include biopsy with corticosteroids, radiation therapy, and chemotherapy. Many PCNSLs respond to corticosteroid sensitively but will relapse rapidly when used alone. Whole-brain radiation therapy alone does not produce remissions but is usually combined with chemotherapy as consolidation therapy, but we should be aware of treatment-related neurotoxicity, especially in elderly patients. Our patient was finally diagnosed subsequent to biopsy. He responded well to the initial chemotherapy and subsequent whole-brain radiation therapy. Today, he is in complete resolution in terms of clinical appearance and MRI imaging.
Lymphoma should be included in the differential diagnosis of lesions involving the hypothalamic/ third ventricular area. Imaging and stereotactic tissue biopsy are of immense help when establishing the diagnosis. Chemoradiotherapy is the treatment of choice.
The authors declared no conflicts of interest.
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Humam Nisar Tanki , Khursheed Nayil Malik , Rumana Makhdoomi  *, Shaheen Feroz  * and Altaf Umar Ramzan 
 Department of Neurosurgery, Sheri-Kashmir-Institute of Medical Sciences, Kashmir, India
 Department of Radiology, Sheri-Kashmir-Institute of Medical Sciences, Kashmir, India
* Corresponding author: Mnayilkhursh@gmail.com
Received: 24 July 2016
Accepted: 28 May 2017
Caption: Figure 1: (a) Non-contrast computed tomography (CT) of the head showing a hyperdense suprasellar mass. (b) Contrast-enhanced CT showed uniform enhancement of the mass.
Caption: Figure 2: Non-contrast T1-weighted axial magnetic resonance imaging (MRI) of the brain showed an (a) isointense suprasellar mass, (b) post-contrast axial and (c) coronal view of MRI showed solid enhancing lesion in suprasellar region (hypothalamic area). (d) Diffusion-weighted images and (e) apparent diffusion coefficient images showing area of restricted diffusion within the mass.
Caption: Figure 3: Photomicrograph showing CD20 positive lymphoma cells, magnification = 40 x.
Table 1: Case reporting of central nervous system lymphoma located in the hypothalamic and/or third ventricular region. Author/ year/ Investigations/ Histopathology No. of cases radiological findings Patrick et al. (6) Lesions in the Fusiform cells of 1989 1 case (30/f) thalamus, cerebellum, histiocytic type-- cingulate gyri, and cerebral lymphoma. hypothalamus. Cerebral spinal fluid (CSF) total protein (1060 mg/L). Chourmouzi et al. (7) Computed tomography Round B-cell 2005 1 case (CT) head revealed 3 lymphoma. cm lobulated suprasellar- hypothalamic mass. Bolanowski et al. (8) Magnetic resonance Lymphoma malignum 2006 1 case (55/m) imaging (MRI)-optic lymphocytic diffusum chiasm infiltration, type B II A. Renal third ventricle tissue showed diffuse compression, malignant lymphomas pituitary gland with regional normal. lymphonodulitis. Hypothyroidism, secondary adrenal insufficiency, hypogonadism, hyperprolactinemia. Rudnik et al. (9) MRI-intrasellar mass Pituitary gland 2007 1 case (37/m) (5 x 4 cm), wide tissue with Large sella, enclosing B-cell malignant hypothalamic lymphoma. infindibulum, optic chiasm, cavernous, and sphenoid sinus, elevated III ventricle. Akhaddar et al. (10) CT/ brain MRI-36 mm Malignant large 2009 1 case (30/F) hypothalamic mass, B-cell lymphoma suprasellar extension (CD20+). and optic chiasm infiltration. Biasiotta et al. (11) Mass lesion in Malignant large 2010 1 case (67/m) hypothalamus. B-cell lymphoma. Coulter et al. (12) MRI-hypothalamic mass Diffuse large B-cell 2010 1 case (63/m) posterior to optic lymphoma. chiasm, floor of III ventricle, extension to infundibulum, Meckel's cave. Takasu et al. (13) 2.8 cm, hypo-hyper Burkitt's lymphoma. 2010 1 case (71/m) intense mass in hypothalamus, third ventricle. CSF culture, staining negative. Chan et al. (14) 2.0-1.8 cm Brain biopsy & 2010 1 case (50/f) suprasellar mesenteric node- hypothalamic mass. diffuse large B-cell Abdominal CT-bulky lymphoma. adenopathy in mesentery, external iliac nodes, mediastinum, Retroperitoneum. Fadoukhair CT-hyperdense mass in Large B-cell et al. (15) 2010 suprasellar region. lymphoma. 1 case (26/f) MRI-enhancing suprasellar mass (9 x 6 mm), thickening of pituitary stalk. Layden et al. (16) MRI-bilateral Large-cell lymphoma. 2011, 1 case (50/m) symmetric hypothalamic lesions extending to optic tracts and chiasma. CT chest -pericardial, pleural effusion. Panhypopituitarism and DI. Schwingel et al. (17) Pineal, hypothalamic Non-Hodgkin lymphoma. 2011, 1 case (51/m) lesions. CT abdomen-splenic lesion. Quigg et al. (18) Cytogenetic studies B-cell lymphoblastic 2011, 1 case CSF-mixed-lineage lymphoma. (toddler) leukemia gene rearrangement. Broussalis MRI-hypothalamic Marginal zone B-cell et al. (19) 2011 lesion extending to lymphoma. 1 case (57/m) mesencephalon, anterior commissure, mammillary bodies. MRI spectroscopy- depressed NAA and elevated choline peak. CT-mediastinal nodes (peribronchial). Antic et al. (20) Focal infiltration of Non-Hodgkins diffuse 2012, 1 case (60/f) hypothalamus and large B-cell lymphoma lateral ventricles, (L5-S1 mass). also L5-S1 mass. Hen et al. 2012, Enhancing dumbell Diffuse large B-cell 1 case (48/m) lesion, 2.4 x 1.2 cm, malignant lymphoma. involving hypothalamus and pituitary. Papanastasiou MRI-pituitary adenoma Chromophobe pituitary et al. (21) 2012 with inhomogeneous adenoma. Diffuse 1 case (60/f) enhancement extending large B-cell non- into suprasellar Hodgkin's lymphoma. region, compressing the optic chiasm and invading left cavernous sinus, pons. Malaise et al. (22) 2.7 cm left Diffuse large B-cell 2012, 1 case (57/m) thalamopedoncular primary cerebral lesion, mass effect lymphoma. on left lateral, third ventricles, hypothalamic and pituitary invasion. Yang et al. (23) Pt 1, MRI-small Pt 1-lymphatic plasma 2013 2 cases nodular lesion under cell lymphoma Pt 2- (20/m, 26/m) hypothalamus (tuber Burkitt's ALL. cinereum) caused by lymphoma. Pt 2-hypophyseal fossa small, high signals from posterior pituitary lost. Author/ year/ Clinical profile Treatment/outcome No. of cases Patrick et al. (6) Thirst, secondary Intranasal 1989 1 case (30/f) amenorrhoea, cranial desmopressin acetate diabetes insipidus, nasal spray. paraesthesia lower Steroids. Died after limbs, unsteady gait, 26 months. ataxic, spasticity, hyperreflexia. Chourmouzi et al. (7) Insidious onset Surgery only. 2005 1 case global pituitary Improved. failure/ hypopituitarism. Bolanowski et al. (8) Lymph node Seven cycles of 2006 1 case (55/m) enlargement, cyclophosphamide bitemporal cncovin (vincristine) hemianopsia, diabetes prednisone (COP) insipidus (DI) with (cyclophosphamide, hypopituitarism vincristine, (weakness, prednisone). hypotension, dry Intraspinal 12 skin, constipation, cycles-(cytarabine, and impotence). Mtx, prednisone). Bilateral kidney Radiotherapy-36 mass, hydrothorax, Gy-20. hydro dihydroxyanth- retroperitoneum. racinedione- intrapleurally. Died. Rudnik et al. (9) Headaches, worsening Endoscopic surgery 2007 1 case (37/m) visual acuity/ chemotherapy- bilateral blurred cyclophosphamide vision, bilateral hydroxydaunomycin visual field defects, (doxorubicin) and bilateral optic oncovin(vincristine) nerve atrophy. prednisone (CHOP) (cyclophosphamide, vincristine, adriamycin, prednisone). Whole- brain radiotherapy (RT)-40 Gy. Improved. Akhaddar et al. (10) Headaches, fever, Refused adjuvant 2009 1 case (30/F) dizziness, worsening treatment. Died. vision, polydipsia, polyuria, dehydration. Biasiotta et al. (11) Difficulty in speech, methotrexate therapy. 2010 1 case (67/m) disorientation, Died. memory loss, seizures and DI, systemic lupus erythematosus (SLE) -30 years. Coulter et al. (12) Syncope, night Not mentioned. 2010 1 case (63/m) sweats, anorexia, postural hypotension, allodynia affecting trigeminal nerve. Panhypopituitarism. Takasu et al. (13) General fatigue, Endoscopic biopsy, 2010 1 case (71/m) disoriented, weakness whole-brain RT of 43 of right arm, DI. Gy-24 sessions + boosters of 12 Gy (10). Chan et al. (14) Night sweats and CHOP chemotherapy, 2010 1 case (50/f) weight Loss, Craniotomy--biopsy. personality changes, Desmopressin for DI, ate and drank ad For central nervous libitum. system (CNS)-high- dose methotrexate ifosfamide, carboplatin, etoposide. Fadoukhair Infertility, Prednisolone 60 mg/ et al. (15) 2010 amenorrhea and day. Stereotactic 1 case (26/f) galactorrhea, biopsy. Died. weakness, headaches, nausea and vomiting, shaking chills, night sweats, weight loss, diplopia. Layden et al. (16) Chest pain, Brain biopsy-primary 2011, 1 case (50/m) hallucinations, CNS B-cell lymphoma. paranoia, polyuria, Chemotherapy. Disease polydypsia, garbled remission. and slurred speech, disorientation. Schwingel et al. (17) Third nerve palsy, Chemotherapy Died 2011, 1 case (51/m) axillary large-cell shortly. non-Hodgkin lymphoma. Quigg et al. (18) Hyperphagia and Induction and 2011, 1 case obesity. Both consolidation (toddler) improved. chemotherapy. Broussalis Olfactory Antidepressants, et al. (19) 2011 hallucination, desmopressin acetate, 1 case (57/m) diplopia, frontal L-thyroxine and cephalgia, short- dimethicone, term memory hydrocortisone, and dysfunction, lack of risperidone. Three appetite, left cycles of cladribine. ptosis, hyperthyreosis, depression. Polydipsia (10 lt), polyphagia, optical hallucinations, illusions. Antic et al. (20) Intense back, left Intravenous (IV), 2012, 1 case (60/f) leg pain, sleep intrathecal disturbances, methotrexate. malaise, nausea/ Improved. vomiting, central DI. Hen et al. 2012, Headache, DI, normal Transnasal- 1 case (48/m) vision. DI and transsphenoidal headache resolved Biopsy. Six cycles IV following therapy. high-dose methotrexate-based regimens, one cycle whole-brain RT. Papanastasiou Generalized muscle Craniotomy and RT. et al. (21) 2012 weakness, headache, Optic nerve 1 case (60/f) right eyelid ptosis. decompression. Amenorrhea, vision Radiotherapy 46 Gy. impairment in right Sublabial eye. transsphenoidal surgery-recurrence. Malaise et al. (22) Confusion, urinary Corticosteroids, IV 2012, 1 case (57/m) incontinence, cytarabine, polyuria, polydypsia, methotrexate, whole/ weight loss, ataxia, brain RT (39 Gy), and paresis of desmopressin oculomotor nerve III. 10 [micro]g/2 days, Central intrathecal hypogonadotropic cytarabine. Improved. hypogonadism and central hypothyroidism. Yang et al. (23) Both had DI. Body Patient 1/0.1 mg 2013 2 cases aches, high fever, desmopressin acetate (20/m, 26/m) weight loss, trade name DDAVP, polyuria, polydipsia, CHOP. Cranial proteinuria. radiation. Patient 2/EPOCH/itoxantrone, cytrabine, and 100 mg/d thalidomide.
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|Title Annotation:||CASE REPORT|
|Author:||Tanki, Humam Nisar; Malik, Khursheed Nayil; Makhdoomi, Rumana; Feroz, Shaheen; Ramzan, Altaf Umar|
|Publication:||Oman Medical Journal|
|Article Type:||Case study|
|Date:||Jul 1, 2018|
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