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)CASE REPORT
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.
DISCUSSION
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.
CONCLUSION
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.
Disclosure
The authors declared no conflicts of interest.
REFERENCES
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(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.
(6.) Patrick AW, Campbell IW, Ashworth B, Gordon A. Primary cerebral lymphoma presenting with cranial diabetes insipidus. Postgrad Med J 1989 Oct;65(768):771-772.
(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.
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(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.
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(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.
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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: Mnayilkhursh@gmail.com
ARTICLE INFO
Article history:
Received: 24 July 2016
Accepted: 28 May 2017
Online:
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.
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 |
| Words: | 3208 |
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