Department of Internal Medicine (A.G., E.A.R.), University of Brescia, 25125 Brescia; and Endocrine Unit, Division of Medicine (M.G., M.D.), Carlo Poma Hospital, 46100 Mantova, Italy
Address all correspondence and requests for reprints to: Dr. Andrea Giustina, Endocrine Section c/o 2a Medicina, Spedali Civili, 25125 Brescia, Italy. E-mail: giustina{at}master.cci.unibs.it
Pituitary masses are diagnosed with increasing frequency due to the progressive refinement of endocrine tests and imaging procedures. Pituitary adenomas are the most common cause of a mass in the sella, accounting for up to 1015% of intracranial neoplasms (1). However, when dealing with abnormal intrasellar masses, a number of different etiologies are possible: germ cell tumor, gliomas, meningiomas, metastatic tumors, vascular lesions, granulomatous, and infectious and inflammatory processes (2).
Lymphomas originating in the parasellar region have been anedoctically reported to be among the most unusual causes of sellar masses. However, during the last decade there have been an increasing number of isolated reports describing new cases of pituitary lymphomas, including a Clinical Case Seminar recently published in JCEM (3). The aim of this report is to put in a clinical perspective all the available data on primary pituitary lymphomas (i.e. without other localization of the disease) described so far, including the features of a recent and unpublished case observed by us.
Here, we show that pituitary lymphomas are not a simple clinical curiosity but a precise, and emerging, entity likely heterogeneous in origin with possible specific risk and pathogenetic factors and distinct clinical features. We also provide elements for the clinician for the differential diagnosis and treatment of pituitary lymphomas. Finally, prognostic and outcome data on affected patients are given in this article. All these elements are put in perspective in the attempt to help endocrinologists in the understanding of pituitary lymphomas and in being prepared to deal with what we think is an emerging clinical entity.
Epidemiology
Intracranial tumors. The frequency of tumors of the central nervous system (CNS) ranges between 3.8 and 5.1 per 100,000 subjects. In the United States, CNS tumors constitute the fourth cause of death in males aged 3554 yr. In Europe, those tumors account for only 2% of all deaths due to cancer (4). On the other hand, pituitary tumors account for about 10% of intracranial neoplasms and have an annual incidence in the general population of about 25 per million (5). Primary CNS lymphoma (PCNSL) is now thought to constitute 3% of all intracranial neoplasms (6).
Intracranial lymphomas. Non-Hodgkins lymphoma (NHL) may involve the CNS either as a primary tumor or after spreading from an established systemic lymphoma. This occurs in 529% of patients with systemic lymphoma during the natural history of the disease and is usually associated with progressive widespread systemic disease (7). PCNSL is a less commonly encountered clinical entity and is defined as lymphoma limited to the cranial-spinal axis without systemic disease. In the past, PCNSL was considered a rare disorder, accounting for 12% of all cases of NHL and fewer than 5% of all cases of primary intracranial neoplasm (7). This frequency has largely increased because of the increasing number of patients with congenital and iatrogenic immunosuppression and acquired immunodeficiency syndrome (AIDS) (8). However, recent data also show an increase in the incidence of primary intracranial malignant lymphomas in immunocompetent individuals (6).
Lymphomas of the pituitary. As far as this last localization
is concerned, 38 cases of hypophyseal lymphoma were found in an autopsy
series of 165 patients (about 23%) who died of hematological
malignancies, although there was no mention of hypopituitarism during
life (9). Recently, some authors have carried out a
clinicopathological examination of brain tissue taken postmortem from
patients with PCNSL to determine the topographic involvement of the
CNS. The pituitary gland was involved in 5 of 22 cases (about 25%) and
particularly the posterior but not anterior lobe (10). In
a recently reported series of 1120 patients undergoing transphenoidal
surgery for sellar masses from January 1981 through May 1998 only a
single lymphoma was diagnosed (less than 1) (2).
Recently, several cases of PCNSL, presenting as pituitary tumor, have
been described. The total number of cases reported in some detail in
the literature is now 24, specifically 14 cases of apparently primary
pituitary lymphoma (2, 3, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) and 10 cases of
secondary localization or infiltration of the sella turcica (10, 23, 24, 25, 26, 27, 28, 29, 30, 31). Our analysis of the main clinical features of primary
pituitary lymphomas is based on the detailed description available in
the literature (Medline search, proceedings of international meetings)
of 13 cases [11 available as full papers (2, 3, 11, 13, 14, 15, 16, 17, 18, 19, 22) and 2 as abstracts (12, 20)]. In fact, for one
case (21) there is no possibility to obtain from the
literature an adequate characterization, which was not the scope of the
original publication reporting the case. Conversely, for the case
observed by us, and reported so far only in abstract form
(20), some details have been added to the present
analysis.
Age- and sex-linked incidence. The annual incidence of malignant lymphomas ranges from 89 per 100,000, with about 75% due to NHL. The male to female ratio is greater than 1.11.3:1 for NHL. The slightly higher number of males with NHL is constant at any age and for all histological kinds. For NHL there is a first incidence peak at the age of 10, a decrease at about 20 yr of age, and a progressive increase until the age of 70 (32). PCNSL can appear at all ages, with peak incidence between the 6th and 7th decade in nonimmunodepressed subjects (33). In these subjects the male to female ratio is 3:2, whereas more than 90% of AIDS patients are males and of younger age (32).
Pituitary tumors are generally benign tumors, although they may show histological evidence of invasion of the capsule or into the surrounding structures. The peak incidence occurs between the ages of 30 and 60 yr, being somewhat earlier in women than men because of the greater frequency of prolactinomas in young women (5).
Lymphocytic hypophysitis has been reported to be predominantly a disease of females, frequently associated with pregnancy or presenting during the postpartum period (in the literature, this association was found in 63% of female patients) (34). The mean age of presentation in females is 35 yr whereas in males it is one decade later (35, 36).
Primary pituitary lymphomas have been predominantly observed in
males (male of female ratio is 2:1) (Fig. 1). The peak incidence of the disease
occurs around the 6th decade of age (Fig. 1
). The mean age of the
patients described so far is 59.46 ± 17.16 yr (mean ±
SD). The age of higher incidence of NHL of the
pituitary is similar to cerebral lymphomas in general as it is the male
prevalence. In the only patients with AIDS reported so far (Table 1
and Ref. 11), the
pituitary lymphoma appeared at a younger age than in the remaining
population, reflecting a similar decrease in the age range of cerebral
NHL in immunodepressed subjects.
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Among the established or hypothetical risk factors for pituitary lymphomas are AIDS, pituitary adenomas, and lymphocytic hypophysitis.
AIDS and other immunodeficiency states. The main reason for the increase in cases of PCNSL in immunodeficient subjects is the AIDS epidemic, and it is probably due to the improved survival of AIDS patients. Two and one half percent of AIDS patients develop PCNSL (37). In autopsy studies involvement of the pituitary has been reported as a result of direct spread from adjacent structures or metastasis from extra neural sites. The tendency of primary central nervous lymphomas to grow in the brain may be explained by the decreased immune surveillance normally found within the CNS. Thus, PCNSL in the patients with AIDS may be the result of a process of uncontrolled Epstein-Barr virus (EBV)-induced B lymphocyte proliferation with possible subsequent neoplastic transformation in an immunologically privileged site in a patient with baseline impaired immune surveillance (7).
Lymphocytic hypophysitis. There has been one previous report suggesting lymphocytic hypophysitis to be a likely risk factor for the development of pituitary lymphoma (22). This possibility is also suggested by the case observed by us (20). Therefore, even with the caution suggested by the limited clinical evidence so far, it can be hypothesized, by analogy with other endocrine gland lymphomas (38), that lymphocytic hypophysitis (17) may be potentially a risk factor for pituitary lymphomas. Prospective studies on the outcome of patients with hypophysitis are needed to possibly confirm this hypothesis.
Pituitary adenomas. Patients with pituitary adenomas were reported to have an increased risk of second malignancies, including lymphoma (39). Furthermore, lymphoma cells possess endocrine hormone receptors, and growth of both T and B lymphoma cells can be stimulated by PRL and other pituitary hormones (40) (a local concentration of pituitary hormones may favor the growth of lymphoma cells). On the other hand, the breaching of the blood brain barrier by the pituitary tumor may also allow easy access of the lymphoma cells to an immunologically privileged site for rapid proliferation (19).
Pathogenesis
Several cases of PCNSL as a concomitant or secondary malignancy following intracerebral or extracerebral neoplasms are on record (41). Often, the preceding tumors had been of high malignancy and treated by chemotherapy and/or radiotherapy thought to have carcinogenic effects on hematopoietic cells (42, 43), possibly associated with genetic predisposition. This explanation is also likely to apply to malignant brain tumors occurring after radiotherapy of benign tumors. However, in the cases reviewed by us and in the patient observed by us no radiotherapy was recorded in the clinical history and therefore, it cannot be implicated in the development of pituitary lymphomas.
Two specific pathogenetic pathways for pituitary lymphomas may be hypothesized:
Hypophysitis in immunocompromised/immunocompetent patients. A policlonal lymphocytic inflammation (mixed T- and B-cell population) may undergo monoclonal expansion with subsequent malignant transformation, possibly triggered by an infectious agent. In fact, transient "sentinel" brain lesions have been observed in immunocompetent subjects to precede PCNSL, and histologically they included inflammatory T cells (44). Because almost all PCNSLs of immunocompromised patients contain genome of the oncogenic EBV (45), it is conceivable that polyclonal inflammatory disorders due to EBV or another herpes virus may undergo monoclonal conversion. In a previous study (22) as well as in the case of pituitary lymphoma by us observed (20) there were histological signs of inflammatory lesion even if there was not previous history of hypophysitis. Moreover, subclinical, smouldering preexisting inflammation cannot be excluded in other cases. It is interesting to hypothesize that what could take place at the pituitary level is an already well described phenomenon at the thyroid level with Hashimotos thyroiditis (HT). Histological features of HT include, as in lymphocitic hypophysitis, diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphillic change, or squamous metaplasia in the epithelial cells (38). An etiologically important role of HT in the development of thyroid mainly B-cell lymphomas has been confirmed by epidemiological studies (46).
Pituitary adenomas. The role of pituitary adenomas in the pathogenesis of pituitary lymphomas is far to be clear, and, therefore, the possible links between these two clinical entities are somewhat hypothetical and not yet proven.
Possible pathogenetic pathways for intraadenomatous lymphoma development include monoclonal growth of T cell-infiltrates, expression of adenoma-specific adhesion molecules, and the mitogenic potential of some pituitary hormones. The expression of mutated adhesion molecule on adenomatous pituitary cells may act as lymphocyte "homing" signals to the adenoma tissue. Lymphoma development could be stimulated by hormones produced by the adenoma. Several hormones [PRL (47, 48), GH (49, 50, 51), and gonadotropins (19, 52, 53)] released by either normal or adenomatous pituitary are known to have mitogenic effects both on lymphoma cells and on normal human lymphocytes.
Clinical presentation
Hypopituitarism. Pituitary lymphomas, similar to
pituitary adenomas, may present with symptoms of anterior pituitary
hormone dysfunction. The developing hypopituitarism associated with
expanding pituitary masses frequently follows a characteristic sequence
involving initially diminished gonadotropin secretion, followed by GH,
TSH, and ACTH deficiency (54). Although this is the
classic order of deficiency, variation in the order of pituitary
hormone failure may occur (55). More than 50% of patients
with primary pituitary lymphomas showed at the time of diagnosis
clinical and/or laboratory evidence of pituitary hypofunction. At the
time of diagnosis five patients (16, 17, 18, 19, 20) showed global
anterior hypopituitarism, whereas three patients had partial
hypopituitarism (3, 13, 15): three had hyperprolactinemia
(13, 15, 17) pointing to a secondary hypopituitarism
presumably due to pituitary stalk compression. Of the patients with
anterior pituitary failure, five also had diabetes insipidus (Table 1).
Therefore, these heterogeneous endocrine findings may suggest different
origins of the lymphoproliferative tissue: extrapituitary (with
hypopituitarism due to pituitary stalk compression or without
hypopituitarism); posterior
hypophysis (with diabetes insipidus); and anterior pituitary
(partial or global anterior pituitary failure).
Neurological findings. Together with hypopituitarism,
the neurological signs and symptoms are those of expanding intracranial
masses with headache, diplopia, and visual field defects and cranial
nerve involvement. Fifty percent of patients with pituitary lymphoma
had visual field defects. Varying degrees of optic chiasm involvement
have been described. Two of 13 patients had bitemporal hemianopsia.
Extension of the pituitary tumor into either the optic nerve or the
optic tracts caused blindness in one patient; overall, three patients
had variable degrees of optic nerve involvement (Table 1). Headache
seems to be the most common neurological presenting symptom for
expanding lymphomas of the pituitary (about 75% of patients) and
results from erosion of the bony sella turcica or stretching of the
diaphragma sellae. No single typical pain pattern is found in pituitary
lymphoma-associated headaches, because not only occipital and
retro-orbital headaches but also bitemporal patterns have been reported
(Table 2
). Cranial nerve involvements due to the pituitary lymphoma
extending laterally into the cavernous sinus have been reported (about
40% of the patients). These findings may also have a more insidious
onset, with variable presentations ranging from diminished abduction of
the ipsilateral eye due to sixth nerve involvement to diplopia
associated with ocular motor nerve compression, or facial pain if the
first and second branches of the trigeminal nerve are affected.
Interestingly, among the neurological signs, the involvement of the
optic chiasm (14, 19) or even of the optic nerve seems not
to have negative prognostic significance (Table 3
).
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Histologically, lymphomas of the CNS and sella resemble
systemic lymphomas. They are almost always NHLs. Most PCNSLs are
high-grade immunoblastic or diffuse large-cell type with a B-cell
immunophenothype. Despite the high-grade histopathological features,
many PCNSLs are arrested at relatively mature stages of differentiation
(56, 57). PCNSLs are largely clonal on the basis of their
monotypic expression of either - or
-light chain
immunoglobulin. Molecular studies have also demonstrated consistent
profiles of light-chain and heavy-chain immunoglobulin gene
rearrangements in primary, recurrent, and metastatic CNS lymphomas.
Unfortunately, not in all cases of primary pituitary lymphomas reported
in the literature is detailed histological description given. However,
of those patients for whom the results of the histological examination
are available (Table 4
), 54% had diffuse
B cell-large lymphoma whereas 24% had T-cell lymphoma of high
malignancy (Fig. 2). In two cases
(20, 22), signs of inflammation were described (Table 4
).
In two patients (16, 19) (Table 4
), coexisting adenomatous
tissue has been found with positive immunoassay for either TSH (and
chromogranin) (Ref. 16 and Table 4
) or FSH (50% of cells)
(Ref. 19 and Table 4
).
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The differential diagnosis includes pituitary and
nonpituitary sellar and parasellar masses. Pituitary tumors may vary a
lot in presentation. Clinical findings depend largely on whether the
tumors are hormone secreting or clinically nonfunctioning, on the size
and pattern of tumor growth, and on whether normal pituitary is
disrupted (54). Nonsecreting pituitary tumors typically
appear with visual compromise, including impairment of the visual
fields and decreased acuity, signs of hypopituitarism, and nonspecific
symptoms such as headache. Modest hyperprolactinemia secondary to
hypothalamic-pituitary stalk compression is common (2).
Pituitary lymphomas as many nonpituitary sellar and parasellar masses,
and similar to pituitary adenomas, may present with symptoms of
anterior pituitary hormone dysfunction. These symptoms include gonadal
dysfunction, secondary hypothyroidism, and, less often, clinical
adrenal cortical insufficiency. Hyperprolactinemia, which may be
asymptomatic or accompanied by hypogonadism, is often found at
presentation of lesions of the sellar region. Clinical diabetes
insipidus at presentation is highly suggestive of a nonpituitary
etiology of a sellar or parasellar mass (2). Diabetes
insipidus may result from involvement or compression of the pituitary
stalk, hypothalamus, or paraventricular region of the third ventricle
by the lesion. In the patients examined by us, diabetes insipidus was
not particularly frequent (less than 50% of patients) but a factor,
when present, associated with poor prognosis. Therefore, based on
clinical presentation, differential diagnosis of pituitary lymphomas is
not easy at best. Severe headache without GH hypersecretion and
coexisting signs of hypopituitarism with diabetes insipidus and/or
cranial nerve involvement should prompt the clinical suspect of a
pituitary lymphoma (but they do not exclude other causes of sellar
masses). As many as 25% of patients with nonpituitary sellar or
parasellar masses have impairment of cranial nerves II, III, IV, and VI
(2). Headache is often a prominent symptom in patients
with large tumors that produce ventricular dilatation. Similar to
pituitary adenomas, many nonpituitary sellar masses may present with
hypopituitarism. Differential diagnosis is difficult on magnetic
resonance imaging (MRI) (Fig. 3). The
sellar region enlargement is suggestive of a pituitary lesion, but the
eroded bone is not particularly helpful in differential diagnosis.
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The differential diagnosis of primary vs. secondary pituitary lymphomas may include a complete neurological staging, including cerebrospinal fluid examination and ophtalmological evaluation with slit-lamp examination to exclude vitreous or retinal involvement. In addition, an abdominopelvic CT scan and bone marrow biopsy may be obtained to exclude systemic lymphoma.
In the series of patients with pituitary lymphomas examined by us, only in one case was the presumptive diagnosis lymphoma of the brain. In the large majority of cases presumptive diagnosis was pituitary adenoma. Confirmation of diagnosis was most frequently obtained with surgery (10 cases).
Treatment and outcome
Neurosurgery.
In PCNSL, in general the role of neurosurgery is that of allowing the histopathological diagnosis mainly via a stereotactic biopsy. In the case of primary pituitary lymphomas the role of neurosurgery seems more important because the mass is, among all other cerebral sites, the easiest to reach via the transphenoidal approach. The clinical presentation of pituitary lymphomas may be similar to that of pituitary invasive macroadenomas. Those pituitary adenomas often cause compression of the optic chiasm and neurological deficits as well as most of primary pituitary lymphomas at presentation. We suggest that in these cases the neurosurgical removal of the mass effect (even if the resection could not be complete) may have a double advantage: to improve the clinical conditions and to allow the histopathological diagnosis. Seldom, particularly when the growing invasive mass does not involve the optic chiasm (lateral and/or inferior expansion), neurosurgical intervention is not performed because it is considered unable to obtain a complete removal of the mass and, therefore, radiation therapy is directly administered. We suggest that in the presence of such masses at least a transphenoidal biopsy should be obtained before any other interventions: this may allow a better (chemotherapy) treatment in case the mass is histopathologically diagnosed as pituitary lymphoma. In the experience obtained so far, pituitary lymphomas presented as large pituitary masses. This finding does not exclude that in the future smaller pituitary lymphomas may be diagnosed; therefore, speculatively, if the pituitary mass is not very large and there is no visual or neurological deficit, it might be appropriate to follow-up the patient and repeat short-term (e.g. three months) MRI and send the patient to the surgeon if a rapidly growing mass is observed. This clinical chance (follow-up) may always be taken with caution due to the almost invariably aggressive features of pituitary lymphomas.
Radiotherapy.
Radiotherapy has been the primary
therapy for PCNSL for many years. Radiation increases survival from 4
months with surgery alone to 1218 months with whole brain
radiotherapy (60). The Radiation Therapy Oncology Group
prospectively studied 41 patients treated with 40 Gy whole brain,
followed by a 20-Gy focal boost. A response was seen in 62% of
patients, but the median survival was only 12.2 months. The addition of
a boost to the area of bulky disease did not improve intracranial
disease control or survival (60). In the examined series
of patients, half of them have been given radiation therapy (Table 2).
Chemotherapy.
Because PCNSL is histologically
similar to systemic NHL, it seemed reasonable to try systemic lymphoma
regimens for PCNSL. To date, no conventional systemic lymphoma regimen
has proved effective against PCNSL. Two multicentered prospective
trials tested preirradiation cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP) or cyclophosphamide, doxorubicin,
vincristine, and dexamethasone, followed by whole brain
radiotherapy (61, 62). CHOP is the optimal combination
regimen for the treatment of advanced systemic NHL.
CHOP/cyclophosphamide, doxorubicin, vincristine, and dexamethasone
failed to produce sustained remissions in PCNSL, and median survival
rates were no better than with brain radiotherapy alone. High-dose
methotrexate was found to be the only independent treatment-related
factor that improves outcome (63). This has led to
experimentation with different regimes, none of which have been studied
in sufficient detail to determine an optimal approach. However,
chemotherapy alone can produce sustained remissions in some patients,
including the elderly population. Considerable improvements in survival
have been accomplished by the addition of chemotherapy to cranial
radiotherapy. In addition, many patients achieve substantial
disease-free survival with chemotherapy alone, and survival is superior
to that with radiotherapy alone (60). About half of the
patients with pituitary lymphoma received chemotherapy, only in three
cases (3, 13, 17) without cranial radiation. Regimens used
were slightly or clearly different in the various cases reported so far
(Table 2). Therefore, the data available do not allow any conclusions
on the best chemotherapy regimen for pituitary lymphomas outcome.
However, due to the overall good response to chemotherapy, every
patient with pituitary lymphoma should be considered for this option as
the first line of therapy. Subsequent cranial radiotherapy may or may
not be necessary depending on the patients clinical condition, age,
and response to initial chemotherapy.
Outcome. Overall, pituitary lymphomas seem to have a better prognosis with respect to all PCNSLs. Approximately 70% of the examined patients had survived quite long (>6 months, where adequate follow-up is available) after the diagnosis, whereas in patients with cerebral lymphomas survival is often less than 6 months (although the improvement of treatment has led to an improved survival also for PCNSL, in general). As in all other malignancies, early diagnosis has to be considered the key to achieve a better outcome. In fact, among cerebral lymphomas, pituitary ones are those that allow the easiest and less invasive diagnostic approach due to the possibility of transphenoidal approach. As mentioned above, when the lesion is already too large to allow complete neurosurgical removal, we propose to obtain in any case as early as possible a sample of the sellar occupying lesion, even only with a minimally invasive transphenoidal biopsy.
Prognostic factors
PCNSL is an important lethal complication in AIDS patients. The presence of prior opportunistic infections, risk factors for AIDS, ethnicity, gender, duration of symptoms before diagnosis, and race did not influence survival. PCNSL is a neoplasm with a very poor prognosis and short survival even with CNS radiation therapy. Also for pituitary lymphomas, which seem to have a better prognosis than PCNSL in general, AIDS seems to be a negative prognostic factor. From the review of all the available reports of pituitary lymphomas it seems that the lesions that certainly or possibly derive from preexisting pituitary adenomas are among those with a better prognosis. Whether the apparently better prognosis of those pituitary lymphomas is due to the intrinsic characteristics of the lesions or to a better response to treatment it remains to be established.
Conclusions
Primary pituitary lymphomas are an emerging clinical entity with an increasing number of well described cases in the last decade (3, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22), as well as reported in a large series of pituitary masses (2). This report is, to our knowledge, the first attempt to put together all the available information on this subtype of cerebral lymphoma, the main peculiarities of which are pathogenesis, clinical presentation, and even prognosis. The data reported so far suggest that pituitary lymphomas are not a unique clinical entity but that they may represent the final presentation of different processes with either hypophyseal or extra hypophyseal origin. We think that the most interesting lines of research in this field will be the understanding of the fine pathogenetic mechanisms that lead to this disease and consequently the reason of the apparently better prognosis with respect to cerebral lymphomas in general. Finally, further information from additional cases of primary pituitary lymphomas need to be collected to validate the data obtained so far and the interpretations given by us before they can be translated into the clinical practice.
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We thank Dr. A. Bertuzzi, S. Fazion, G. C. Pascal, M. L. Spina, F. Smerieri, R. Caudana, and L. Ventura for invaluable help in the clinical work; and Dr. P. Iuzzolino and S. Turazzi for help characterizing the case of pituitary lymphoma. We are indebted to Dr. P. Iuzzolino for kindly providing histopathology pictures and to Dr. R. Caudana and F. Smerieri for the MR imaging pictures. A.G. and M.D. are also indebted to Prof. G. Romanelli for scientific advice and fruitful discussion. M.G. is indebted to Prof. A. Velardo for scientific guidance. A.G. is supported by funds of Ministero Universitá e Ricerca Scientifica e Tecnologica, Regione Lombardia, and University of Brescia.
Footnotes
Abbreviations: AIDS, Acquired immunodeficiency syndrome; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CNS, central nervous system; CT, computed tomography; EBV, Epstein-Barr virus; HT, Hashimotos thyroiditis; MRI, magnetic resonance imaging; NHL, non-Hodgkins lymphoma; PCNSL, primary CNS lymphoma.
Received January 5, 2001.
Accepted June 6, 2001.
References