Acta Neurochir (2008) 150:921–924 DOI 10.1007/s00701-008-0012-8
SHORT ILLUSTRATED REVIEW
Intrasellar plasmacytoma: an unusual presentation of multiple myeloma E. Yaman & M. Benekli & U. Coskun & K. Sezer & B. Ozturk & A. O. Kaya & R. Yildiz & O. Uluoglu & S. Buyukberber
Received: 11 October 2007 / Accepted: 13 May 2008 / Published online: 23 August 2008 # Springer-Verlag 2008
Abstract Introduction Plasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities. Literature review We reviewed the pertinent literature and discuss here in the light of an illustrative case of our own. Discussion A 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain. Further studies confirmed the diagnosis of multiple myeloma. The patient was successfully treated with radiotherapy followed by systemic chemotherapy. Because they have different therapeutic implications, extramedullary plasmacytomas involving pituitary gland should be considered in the differential diagnosis of a nonfunctioning pituitary mass. Keywords Pituitary mass . Plasmacytoma . Multiple myeloma E. Yaman : M. Benekli : U. Coskun : B. Ozturk : A. O. Kaya : R. Yildiz : S. Buyukberber (*) Department of Medical Oncology, Gazi University Faculty of Medicine, Besevler, Ankara, Turkey e-mail:
[email protected] K. Sezer Department of Endocrinology and Metabolic Diseases, Mersin University Faculty of Medicine, Mersin, Turkey O. Uluoglu Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey
Introduction Multiple myeloma is a neoplastic disorder arising from plasma cells in the bone marrow. Plasma cell tumors, plasmacytomas, are uncommon in the brain and occur usually in the leptomeningels with or without parenchymal involvement. Extramedullary plasmacytomas are very rarely located in the sella and can be misdiagnosed as a nonfunctioning pituitary adenoma. We reviewed the literature to find similar cases of intrasellar plasmacytomas and report an illustrative case with multiple myeloma who presented with a sellar plasmacytoma behaving like a pituitary adenoma.
Literature review A literature search was performed using Medline database in PubMed (http://www.ncbi.nlm.nih.gov/sites/entrez/). The keyword combinations used for this search were “myeloma” or “plasmacytoma” and “sella” or “hypophysis” or “pituitary”. Identified reports were evaluated meticulously to compose this review.
Analysis The search up to September 2007 revealed 21 previous reports describing patients with a solitary plasmacytoma or multiple myeloma presenting with sellar mass. The patients’ characteristics are summarized in Table 1. The mean age of patients was 55.8 years (range, 35–70). Twelve were women and nine were men. The majority of patients (66.7%) presented with headache. Other common symptoms included diplopia (57.1%) and visual loss (9.5%).
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Table 1 Clinical features of the patients reported in the literature Case Age Sex Symptom
Cranial nerve involved
Treatment
Outcome
Authors
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
65 62 64 73 47 47 57 44 66 42 42 62 34 50 58
M F F F M M M M M M M M F F F
Left III Right III, IV I Left III, IV, VI Right III, IV, VI Left III, VI Left III, IV Left III Left IV None Left VI Left III, IV Left III, IV Left VI None Right VI partial Right V partial Left VI, VII
RT RT RT Unknown Unknown RT + CT RT + CT Unknown RT RT RT + CT Unknown RT RT RT
Progression to MM Progression to MM Progression to MM MM at presentation MM at presentation Progression to MM MM at presentation Progression to MM Plasmacytoma Progression to MM Progression to MM MM at presentation Plasmacytoma Plasmacytoma Plasmacytoma
Sanchez et al. [17] Poon et al. [16] Urbanski et al. [21] Vallat et al. [22] Hornedo et al. [8] Vaquero et al. [23] Kerty et al. [12] Estopian et al. [4] Evans et al. [5] Bitterman et al. [2] Harrison et al. [7] Dhahani et al. [3] Jacuet et al. [9] Losa et al. [13] Juneat et al. [10]
16 17 18 19 20 21 22
51 75 53 57 65 57 70
F F F F F F F
Unknown Right III, IV, VI None Right VI Left VIII Right V partial None
RT + CT RT + CT RT Unknown RT RT + CT + PBSCT RT + CT
Plasmacytoma MM at presentation Plasmacytoma Plasmacytoma Plasmacytoma MM at presentation MM at presentation
Bindal et al. [1] Kanoh et al. [11] Mandagere et al. [14] Weber et al. [24] McLaughin et al. [15] Sinnot et al. [20] Our case
Headache, diplopia Headache, visual loss Diplopia Diplopia Ptosis Diplopia Headache, diplopia Headache, visual loss Headache, diplopia Headache, left eye pain Headache, blurred vision Headache, diplopia Craniofacial pain Diplopia Headache, diplopia, facial dumbness Diplopia Headache, diplopia Headache Headache, diplopia, visual loss Headache, hearing loss Headache, facial numbness Headache
MM Multiple myeloma, RT radiotherapy, CT chemotherapy, PBSCT peripheral blood stem cell transplantation
Cranial nerve palsies were present in 17 of 21 (81%) patients. Most commonly involved nerves were abducent (38%), trochlear (38%), and oculomotor (38%) nerves. Radiologically, all tumors mimicked a nonfunctioning pituitary adenoma with sellar destruction. Unfortunately, there was no information about hypopyhsial hormonal profile in five patients. In four patients, hypopyhsial hormone abnormalities were detected. As in our patient, two patients had hyperprolactinemia. In one patient, both adrenocorticotropic hormone (ACTH) and thyrotropinreleasing hormone were elevated, and in the other patient, primary hypothyroidism was observed. In five patients, the initial diagnosis was of a chromophobe adenoma; however, after detailed pathological evaluation with immunohistochemical and electron microscopic studies, the diagnosis of plasmacytoma was made. After initial surgical intervention, radiotherapy was administered in ten (48%) patients, and both chemotherapy and radiotherapy were administered in five (24%) patients. In one patient, autologous stem cell transplantation was performed after chemotherapy and radiotherapy. There was no information about treatment in five patients. Six of these 21 patients were known to have multiple myeloma at the time of diagnosis. In the follow-up, eight patients did not develop multiple myeloma and behaved clinically as a solitary plasmacytoma, while seven patients progressed to myeloma during follow-up.
Illustrative patient A 70-year-old white woman presented with a history of headache and diplopia. She denied any other neurological symptoms. Her complaints started approximately 7 months previously. She had a history of a pathological fracture of right humerus 2 months previously attributed to senile osteoporosis. On admission, physical and neurological examinations were normal. She had a mild anemia with a hemoglobin level of 11.5 g/dl. Blood chemistry analyses were normal. Serum prolactin level was slightly elevated at 48 ng/ml, but other hypophysial hormones were within normal limits. Magnetic resonance imaging (MRI) of the brain showed a 5×3.5×3.5-cm mass destroying the floor of sella and infiltrating the clivus and sphenoid sinus. The tumor had spread to the posterior ethmoid sinuses, causing posterior displacement of both carotid arteries. The lesion was isointense with a dense contrast enhancement on T1weighted images (Fig. 1). The presumptive diagnosis was of a nonfunctioning pituitary adenoma, and transsphenoidal gross excision was performed. The histopathology of the biopsy specimen showed a pituitary adenoma. Immunohistochemistry (IHC) stainings were not performed. Three months later, the patient was re-admitted with headache and diplopia. Her physical examination showed diplopia without any other pathological findings. Sellar MRI showed a new mass measuring 5×5 cm in diameter, with
Intrasellar plasmacytoma
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Fig. 1 T1-weighted images of a coronal view and b sagittal view of the MRI scan of the brain showing pituitary mass lesion with destruction of the sellar floor on the first admission (arrows)
destruction of floor of sella and extension into the sphenoid sinus. The lesion had dense contrast enhancement. There was no evidence of endocrine dysfunction with normal anterior pituitary hormones. The mass was excised via a transsphenoidal approach. Histopathological examination of the tumor showed a plasmacytoma with diffuse positive staining for CD138 and kappa light chain. Re-examination of the previous specimen showed the same architecture and staining pattern. Serum protein electrophoresis detected a monoclonal gamma peak with IgG kappa type M protein on serum immunofluorescence electrophoresis. Urine was negative for Bence–Jones proteinuria. Beta 2 microglobulin level was 3.2 mg/dl. Bone radiographs revealed diffuse lytic lesions involving the skull, left radius, right femur, right humerus, and vertebral column. Bone marrow biopsy showed plasma cell infiltration. The diagnosis of multiple myeloma with involvement of the pituitary gland was made. Radiation therapy was given to the sella and the boney areas at risk of fracture. Subsequently, systemic chemotherapy consisting of melphalan and prednisone was given for 6 cycles. The patient remains in remission 22 months after the therapy.
Discussion A plasmacytoma involving the pituitary gland is exceedingly rare. Most common tumors of hypophysis are pituitary adenomas, whereas plasma cell dyscrasias rarely involve the hypopysis [6]. No instance of pituitary involvement was reported in the series of Silverstein et al. of 273 patients with multiple myeloma and neurological involvement, 3% of whom presented with an intracranial mass [19]. Sellar plasma cell tumors can mimic nonfunctioning pituitary macroadenomas clinically and radiologically, and the light microscopic appearances may be indistinguishable from those of an immature plasmacytoma, unless specific IHC stainings are performed. In the largest series of sellar masses reported up to date, 47 of 1,937 cases were misdiagnosed as an adenoma [18]. Headache, diplopia, and visual disturbances were the most common presenting symptoms. The majority of the patients had intact anterior pituitary function, as in our patient. Differentiation of the cause of a sellar mass is of importance because treatment and prognosis differ accordingly.
Table 2 Immunohistochemical analysis for sellar tumors Tumor
S- Cytokeratin Vim EMA Chr Syn CEA TTF- GCDFP- GFAP βCD CD Immunoglobulins Pituitary 100 A 1 15 HCG 138 79a (kappa or lambda) hormones (GH, FSH, LH, ACTH, TSH)
Pituitary adenoma Craniopharyngioma Meningioma Chordoma Plasmacytoma Germ cell tumor Metastatic tumors
± − − − − ± −
± − ± ± − − −
± ± ± ± − − ±
± − ± ± − − −
± ± ± ± ± − −
± − − − − − −
+ − − − − − −
− − − − − − ±
− − − − − − ±
− − − − − − ±
± − − − − − −
± − − − − ± −
− − − − ± − −
− − − − ± − −
− − − − ± − −
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Craniopharyngioma, meningiomas, chordoma, germ cell tumors, and metastatic epithelial tumors can all cause an intrasellar mass. Although a plasmacytomas are rare causes of a sellar mass, they should be always kept in mind. Moreover, poorly differentiated plasma cells sometimes resemble those of an adenoma. Another important problem is the removal of inflammatory mucosal cells that can also contain reactive plasma cells. When an increased plasma cell ratio is detected, a detailed examination for systemic myeloma manifestations must be done. Histopathological examination is required for a definitive diagnosis. Unfortunately, light microscopic examination may not always be useful in the diagnosis of a sellar masse, and immunohistochemical analysis is the ‘gold standard’ method for definitive diagnosis. The stainings, which are helpful in differential diagnosis of sellar masses, are summarized in Table 2. We demonstrated diffuse positive staining of tumor cells with CD138 and kappa light chains in our patient. Immunohistochemical staining and electron microscopic examinations aid in the differential diagnosis so that staining for the pituitary hormones and alpha subunit must be done in every patient to confirm the diagnosis of an adenoma. A solitary plasmacytoma involving the pituitary gland without systemic myelomatous dissemination is rare. Therefore, a search for an occult myeloma must be performed in these patients. In our patient, there was no clinical suspicion at first admission. The patient’s serum protein, albumin, creatinine, and calcium levels were in normal limits. A diagnosis of plasmacytoma and coexistent myeloma was made only after recurrence of the pituitary mass. Approximately 50% of plasmacytomas progress to overt multiple myeloma in 10-year follow-up, and 10% of them recur with a plasmacytoma. Because treatment and prognosis differ, it is important to detect concurrent multiple myeloma. In conclusion, although multiple myeloma involving pituitary gland is rare, it must be considered in the differential diagnosis of a nonfunctioning pituitary mass. A hypophysial mass with a normal anterior pituitary hormonal profile should alert the physician to the possibility of a diagnosis other than a chromophobe adenoma.
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Comment This is interesting short review of the differential diagnosis of pituitary masses. I believe it is a paper that is worth being added to the current literature as a reminder that not all pituitary masses are adenomas. Siviero Agazzi
