| Abstract|| |
A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL) of pituitary was made. Our patient's condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.
Keywords: Intravascular large B-cell lymphoma, lymphoma, pituitary
|How to cite this article:|
Anila K R, Nair RA, Koshy SM, Jacob PM. Primary intravascular large B-cell lymphoma of pituitary. Indian J Pathol Microbiol 2012;55:549-51
| Introduction|| |
Intravascular large B-cell lymphoma (IVLBCL) is considered to be a rare type of extra-nodal large B-cell lymphoma in the World Health Organization (WHO) classification. It is characterized by the selective growth of lymphoma cells within the lumina of capillaries with exception of larger arteries and veins.  The first case of IVLBCL was described by Pfleger and Tappeiner  in 1959. Two clinical variants have been described, Western and Asian forms. The neurologic and dermatologic signs described as specific to IVLBCL in Western countries are due to occlusion of capillaries by neoplastic cells in these organs. In addition, a considerable number of patients with IVLBCL present with nonspecific clinical manifestations including fever, malaise, pancytopenia, and hepatosplenomegaly associated with hemophagocytic syndrome. These cases are considered as Asian variant of IVLBCL because of their relatively high prevalence in Asian countries. 
| Case Report|| |
A 68-year-old woman presented with altered sensorium and fever for the past 2 months. She also had nonspecific complaints of fatigue, sleep disturbance, polyuria, and polydypsia for the past two months. Her laboratory investigation showed anemia and thrombocytopenia. Her erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) values were raised. Biochemical evaluation showed hypopitutarism with decreased cortisol (4.8 μg/dl), leutinising hormone (0.12 miu/ml), follicle stimulating hormone (1.55 miu/ml), and thyroid stimulating hormone (0.97 miu/l) levels. Her serum prolactin value was within normal limits. She also had electrolyte imbalance with hyponatremia and hypomagnesaemia.
Her HIV, HbsAg, and HCV status were negative. An ultrasound examination of abdomen was done which failed to pick up any significant abnormality. Computed tomography (CT) and magnetic resonance imaging (MRI) of brain showed a mass lesion in sella measuring 1.3 × 1.3 × 1.1 cm [Figure 1]. There was involvement of the infundibular stalk also. With a radiological diagnosis of pituitary macro adenoma the patient was taken up for trans-sphenoidal biopsy. The tissue from the sellar mass measured 0.5 × 0.2 × 0.2 cm. A bone marrow study was also done.
|Figure 1: Mid-sagittal postcontrast images of the brain showing an enhancing pituitary mass lesion with enhancing altered signal intensity replacing the fatty marrow in the adjacent clivus suggestive of involvement|
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Sections from sellar mass showed pituitary tissue with tumor cells lodged mainly within the lumina of small vessels. The tumor cells were large with prominent nucleoli [Figure 2]. Immunohistochemistry showed tumor cells to be positive for CD20, CD5, MUM-1, and bcl2 [Figure 3]a-d. Tumor cells were negative for CD10 and bcl6. A CD31 immunostaining was done to highlight the intravascular location of tumor cells [Figure 4]. With the histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma of pituitary was given. Bone marrow biopsy was studied with hematoxylin and eosin (H and E) and CD20 immunostaining which failed to reveal involvement by IVLBCL.
|Figure 2: Section from pituitary shows tumor cells within vascular lumens (H and E, ×400)|
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|Figure 3: (a) Tumor cells are positive for CD 20 (IHC, ×400). (b) Tumor cells are positive for CD 5 (IHC, ×400). (c) Tumor cells are positive for MUM-1 (IHC, ×400). (d) Tumor cells are positive for Bcl2 (IHC, ×400)|
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|Figure 4: CD 31 staining highlights the intravascular location of tumor cells (IHC ×400)|
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| Discussion|| |
IVLBCL is an unusual subtype of extra-nodal large B-cell lymphoma that generally is a systemic disease with a predilection for skin and CNS involvement. Although there are several case reports and studies of IVLBCL in the literature, according to our knowledge, this is the first reported case of primary IVLBCL of pituitary. Apart from the sellar mass a detailed examination of our patient failed to reveal any lymphadenopathy or organomegaly. A bone marrow study was also normal. We came across two case reports of intravascular lymphoma involving pituitary in the literature. But both these cases were not primary pituitary lymphoma. In one case there was no histopathological confirmation of the involvement of pituitary. In this particular case the patient had IVLBCL of breast along with a sellar mass. On initiation of therapy the sellar mass decreased in size; hence the authors had concluded the pituitary mass to be IVLBCL.  In another case report of intravascular lymphoma of natural killer (NK) cell type the authors have demonstated disseminated disease at autopsy wherein pituitary was also involved but the patient had not presented with a sellar mass.  Lymphomas of the pituitary are rare. Radiological differentiation from an adenoma of pituitary is virtually impossible. Hence histopathological evaluation is essential for diagnosis.
The symptoms in patients with IVLBCL are mainly due to occlusion of the small vessels in the organs affected by tumor cells. Rare cases have been described in immunosuppressed patients, including patients with AIDS or after transplantation. There has been a case report of IVLBCL in Kaposi sarcoma lesions in a patient with AIDS.  Rarely, vascular channels within cutaneous hemangiomas might exhibit IVL.  Hematologic findings include pancytopenia, isolated anemia, thrombocytopenia or leucopenia, and autoimmune hemolytic anemia and diffuse intravascular coagulation. In our case the patient had anemia and thrombocytopenia. The bone marrow involvement can be subtle and can be missed if careful screening is not done.
There are two case reports of pituitary lymphoma presenting with PUO and hypopitutarism in the literature. , In our case also the patient had fever resistant to treatment for a period of 2 months and biochemical evaluation showed hypopituitarism. Several disease processes can manifest themselves as fever and a sellar mass, including lymphomas. Surgical biopsy is necessary to make a diagnosis and distinguish this process from the more common pituitary adenoma. Intravascular large B-cell lymphoma is often not diagnosed sufficiently early due to the exclusive intravascular growth pattern of the tumor cells. The very poor prognosis in these patients is partly due to frequent delays in diagnosis and initiation of therapy due to their extraordinary presentation. Since vessels of all organs may be affected, many different signs can be observed. The affinity of IVLBCL to vascular structures may be due to defect in homing receptors on the neoplastic cells such as lack of CD29 and CD54. 
According to a study by Murase et al. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10 negative IVLBCL.  However they concluded that there was no significant difference in prognosis between CD5 positive and CD5 negative IVLBCL. In our case CD20, CD5, MUM-1, and bcl2 were positive. Bcl6 and CD10 were negative. According to WHO, almost all cases of CD10 negative IVLBCL are MUM-1 positive. Occasional case of intravascular T-cell or NK-cell lymphoma have been reported.  It is better to consider such cases as a different entity separate from IVLBCL.
IVLBCL has a fulminant clinical course. The initiation of an intensive diagnostic work-up is of utmost importance in the diagnosis of this entity since a potentially curative therapeutic option is available, but only if the diagnosis is made at an early stage of the disease. We would also like to highlight that pyrexia of unknown origin (PUO) is a common feature in these cases. Our patient unfortunately succumbed to her disease before therapy could be initiated.
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Rekha A Nair
Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]