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Primary Hypothalamic Lymphoma in an Adult Male: A Case Report and Literature Review.

Primary central nervous system (CNS) lymphomas form 0.85-2.0% of all primary brain tumors. (1) The most common location of primary CNS lymphomas is the periventricular area. (2) The hypothalamus is one of the rare locations of lymphoma in adults. Other lesions that can involve the hypothalamus are chordoid glioma, pituitary mass, metastasis, and meningioma. (3)


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.


(1.) Yasargil MG. Primary CNS non-Hodgkin lymphoma and primary intracranial sarcoma. In: Microneurosurgery. Stuttgart, New York: Georg Thieme Verlag; 1996. P. 375-378.

(2.) Lanzieri CF, Sabato U, Sacher M. Third ventricular lymphoma: CT findings. J Comput Assist Tomogr 1984 Aug;8(4):645-647.

(3.) Pomper MG, Passe TJ, Burger PC, Scheithauer BW Brat DJ. Chordoid glioma: a neoplasm unique to the hypothalamus and anterior third ventricle. AJNR Am J Neuroradiol 2001 Mar;22(3):464-469.

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(5.) Alic L, Haid M. Primary lymphoma of the brain: a case report and review of the literature. J Surg Oncol 1984 Jun;26(2):115-121.

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(7.) Chourmouzi D, Boulogianni G, Delaroudis S, Drevelegas A. Hypopituitarism due to hypothalamic B-cell lymphoma. JBR-BTR 2005 May-Jun;88(3):116-117.

(8.) Bolanowski M, Kuliszkiewicz-Janus M, Sokolska V. Diffuse malignant lymphoma type B with optic chiasm infiltration, visual disturbances, hypopituitarism, hyperprolactinaemia and diabetes insipidus. Case report and literature review. Endokrynol Pol 2006 Nov-Dec;57(6):642-647.

(9.) Rudnik A, Larysz D, Blamek S, Larysz P, Bierzynska-Macyszyn G, Wlaszczuk P, et al. Primary pituitary lymphoma. Folia Neuropathol 2007;45(3):144-148.

(10.) Akhaddar A, Baite A, Naama O, Elmostarchid B, Safi L, Boucetta M. Hypothalamic lymphoma with symptoms mimicking pituitary apoplexy. Intern Med 2009;48(6):491-492.

(11.) Biasiotta A, Frati A, Salvati M, Raco A, Fazi M, D'Elia A, et al. Primary hypothalamic lymphoma in a patient with systemic lupus erythematosus: case report and review of the literature. Neurol Sci 2010 Oct;31(5):647-652.

(12.) Coulter I, Garrioch S, Toft A. An atypical cause of trigeminal neuralgia and panhypopituitarism. Br J Radiol 2010 Dec;83(996):1087-1089.

(13.) Takasu M, Takeshita S, Tanitame N, Tamura A, Mori M, Fujihara M, et al. Case report. Primary hypothalamic third ventriclular Burkitt's lymphoma: a case report with emphasis on differential diagnosis. Br J Radiol 2010 Feb;83(986):e43-e47.

(14.) Chan TW, Hoskins P. Panhypopituitarism secondary to hypothalamic involvement in a woman with diffuse large B-cell lymphoma. J Clin Oncol 2010 Apr;28(11):e165-e166.

(15.) Fadoukhair Z, Amzerin M, Ismaili N, Belbaraka R, Latib R, Sbitti Y, et al. Symptomatic hypopituitarism revealing primary suprasellar lymphoma. BMC Endocr Disord 2010 Nov;10:19.

(16.) Layden BT, Dubner S, Toft DJ, Kopp P, Grimm S, Molitch ME. Primary CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus. Pituitary 2011;14(2): 194-197.

(17.) Schwingel R, Reis F, Zanardi V, Queiroz L, Franca M Jr. Atypical sites of lymphoma in the central nervous system. Arq Neuropsiquiatr 2011 Jun;69(3):566-567.

(18.) Quigg TC, Haddad NG, Buchsbaum JC, Shih CS. Hypothalamic obesity syndrome: rare presentation of CNS+ B-cell lymphoblastic lymphoma. Pediatr Blood Cancer 2012 Nov;59(5):930-933.

(19.) Broussalis E, Kraus J, Kunz AB, Luthringshausen G, McCoy M, Muss W, et al. Cerebral localized marginal zone lymphoma presenting as hypothalamic-pituitary region disorder. Case Rep Neurol 2011 May;3(2):129-135.

(20.) Antic D, Smiljanic M, Bila J, Jankovic S, Todorovic M, Andjelic B, et al. Hypothalamic dysfunction in a patient with primary lymphoma of the central nervous system. Neurol Sci 2012 Apr;33(2):387-390.

(21.) Papanastasiou L, Pappa T, Dasou A, Kyrodimou E, Kontogeorgos G, Samara C, et al. Case report: Primary pituitary non-Hodgkin's lymphoma developed following surgery and radiation of a pituitary macroadenoma. Hormones (Athens) 2012 Oct-Dec;11(4):488-494.

(22.) Malaise O, Frusch N, Beck E, Servais S, Caers J, Caers J, et al. Panhypopituitarism and diabetes insipidus in a patient with primary central nervous system lymphoma. Leuk Lymphoma 2012 Dec;53(12):2515-2516.

(23.) Yang J, Zhao N, Zhang G, Zheng W. Clinical features of patients with non-Hodgkin's lymphoma metastasizing to the pituitary glands. Oncol Lett 2013 May;5(5):1643-1648.

(24.) Sklar EM, Schatz NJ, Glaser JS, Sternau L, Seffo F. Optic tract edema in a meningioma of the tuberculum sellae. AJNR Am J Neuroradiol 2000 Oct;21(9):1661-1663.

(25.) Makhdoomi R, Nayil K, Rayees A, Kirmani A, Ramzan A, Khalil MB, et al. Primary CNS lymphoma in immunocompetent : a review of literature and our experience from Kashmir. Turk Neurosurg 2011 Jan;21(1):39-47.

(26.) Gerstner ER, Carson KA, Grossman SA, Batchelor TT. Long-term outcome in PCNSL patients treated with high-dose methotrexate and deferred radiation. Neurology 2008 Jan;70(5):401-402.

Humam Nisar Tanki [1], Khursheed Nayil Malik [1], Rumana Makhdoomi [1] *, Shaheen Feroz [2] * and Altaf Umar Ramzan [1]

[1] Department of Neurosurgery, Sheri-Kashmir-Institute of Medical Sciences, Kashmir, India

[2] Department of Radiology, Sheri-Kashmir-Institute of Medical Sciences, Kashmir, India

* Corresponding author:


Article history:

Received: 24 July 2016

Accepted: 28 May 2017


DOI 10.5001/omj.2018.63

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.
                        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
                         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.
                          secondary adrenal

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

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

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

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,

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
                               and DI.

Schwingel et al. (17)   Pineal, hypothalamic    Non-Hodgkin lymphoma.
2011, 1 case (51/m)          lesions. CT

Quigg et al. (18)        Cytogenetic studies    B-cell lymphoblastic
2011, 1 case              CSF-mixed-lineage           lymphoma.
(toddler)                   leukemia gene

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

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.
                          hypothalamus and

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,

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,

Chourmouzi et al. (7)      Insidious onset          Surgery only.
2005 1 case               global pituitary            Improved.

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)
                                                 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,

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.

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

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

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,

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,

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.
                         Polydipsia (10 lt),
                         polyphagia, optical

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
                                                 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

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

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
                                                 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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