Sellar solitary plasmacytoma progressing to multiple myeloma: a case report and literature review.

Sellar plasmacytoma is a rare cause of sellar lesions. Preoperative diagnosis remains a challenge. We present a 34-year-old Chinese woman with a 25-day history of headache and diplopia. A physical examination revealed incomplete left abducens nerve palsy. The initial diagnosis was invasive pituitary adenoma. The patient's condition deteriorated suddenly the day before the arranged operating date, with the hemoglobin level declining from 113 to 70 g/L. The operation was cancelled and further studies confirmed the diagnosis of sellar solitary plasmacytoma that progressed to multiple myeloma. After undergoing radiotherapy, high-dose chemotherapy, and autologous peripheral blood stem cell transplantation, complete remission was achieved on 4 years follow-up. We reviewed the pertinent literature and reached the following conclusions: sellar plasmacytomas with development of multiple myeloma on follow-up more likely happened in men than in women; and if the sellar plasmacytoma does not compress the cranial nerve, transsphenoidal resection should be cautious because the systemic treatment with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation may be more effective with little invasion.

INTRODUCTION

Plasma cell neoplasm is characterized by the neoplastic proliferation of a single clone of plasma cells, which can present as a single lesion (solitary plasmacytoma) or as multiple lesions (multiple myeloma, MM).[1] Plasmacytomas are infrequently located in the brain and occur usually in the leptomeninges with or without parenchymal involvement.[2] And sellar plasmacytoma mimics other sellar mass clinically and radiologically, especially the pituitary adenoma, which leads to high misdiagnosis preoperatively and even postoperatively.[3] However, therapy strategies and prognosis differ from each sellar mass. We present an illustrative case of a patient with sellar plasmacytoma suddenly progressing to MM and review the pertinent literature.

METHODS

To identify studies for inclusion in this review, 2 authors independently searched PubMed, the Cochrane Central Database of Controlled Trials, and Embase for relevant studies published up to November 2013. The search was limited to studies conducted in humans. No language restriction was imposed. Search terms were individualized for each database. Search terms used included [“plasmacytoma” OR “multiple myeloma” OR “solitary plasmacytoma” OR “Plasma cell neoplasm”] AND [“sellar lesion” OR “sella turcica” OR “sellar mass” OR “sellar” OR “sellar tumor” OR “skull” OR “cranial”]. We also searched the proceedings of major relevant conferences, trial databases, the reference lists of identified trials, and major reviews. Informed consent was obtained from the patient.

CASE REPORT

A previously healthy 34-year-old woman was referred to our department on February 2010 with a 25-day history of headache and diplopia. A physical examination revealed incomplete left abducens nerve palsy. No systemic symptoms and signs were detected. Blood tests revealed normal biochemical, pituitary hormonal, and hematological parameters on admission. Magnetic resonance imaging (MRI) showed an irregular intrasellar mass with suprasellar and parasellar extension. Relatively low intensity on T1-weighted images and iso-intensity on T2-weighted images, with nonuniform enhanced characteristics were found (Figure 1). Computed tomography (CT) scanning of the brain showed diffuse and irregular bony destruction of the sellar area (Figure 2). The initial diagnosis was invasive pituitary adenoma. The clinical situation deteriorated suddenly the day before the arranged operating date, with progressing pale and severe retro-orbital pain of the left eye. Emergency blood test revealed moderate anemia (hemoglobin 70 g/L, reference 110–155 g/L), hypercalcemia (3.20 mmol/L, reference 2.25–2.75 mmol/L), and renal impairment. The operation was cancelled immediately. A bone scan showed sellar hypermetabolic lesion and proliferative changes throughout the skeleton (Figure 3). λ Serum light chain (3.3 g/L, reference 0.9–2.1 g/L) was high, and the ratio of k/λ serum light chain was 0.55, below the reference range (1.47–2.95). Urine test of Bence-Jones proteins was positive. Serum beta-2 microglobulin level was high (9.97 mg/L, reference 1.28–1.95 mg/L). A final diagnosis of sellar solitary plasmacytoma progressing to MM (λ type) was made. Localized irradiation (40–50 Gy) for sellar plasmacytoma and high-dose vincristine, adriamycin, dexamethasone chemotherapy (vincristine, doxorubicin, and dexamethasone) followed by autologous peripheral blood stem cell transplantation (APBSCT) were undertaken. The patient was followed up for 4 years with no symptoms or signs, and bone marrow aspiration revealed complete remission. Brain MRI revealed that the sellar tumor mass had significantly shrunk (Figure 4).

FIGURE 1

T2-weighted images of (A) axial view and T1-weighted images of (B) sagittal view of the MRI scan reveal an irregular mass in the sella turcica with soft tissue intensity. The mass extends into the parasella somewhat heterogeneously enhanced by Gd on (C) coronal view (arrows).

FIGURE 2

Bone window of an (A) axial CT scan demonstrates the bony irregular destruction of the sphenoid compared to the normal (B) image of the skull (arrows).

FIGURE 3

Single-photon emission CT scan of the entire body shows the presence of a hypermetabolic mass lesion in the sella turcica (A) and changes of proliferation throughout the skeleton, which exhibited strong FDG uptake (B).

FIGURE 4

T2-weighted images of (A) axial view and T1-weighted images of (B) sagittal view of the MRI scan reveal that the sellar tumor mass had shrunk (arrows).

DISCUSSION

We present a 34-year-old Chinese woman with initial diagnosis of invasive pituitary adenoma. The day before the scheduled date of surgery, she suddenly felt pale and had a severe headache; subsequent workups confirmed the diagnosis of sellar solitary plasmacytoma that progressed to MM suddenly. If the operation was carried out, moderate anemia might manifest as excessive bleeding during the operation, which would result in improper treatment. Fortunately, after correction of the diagnosis, the patient underwent radiotherapy (RT) for sellar plasmacytoma and high-dose chemotherapy and APBSCT for MM, and was alive with complete remission on a 4-year follow-up.

A review in 2012 collated all reported cases of plasmacytoma involving the sella turcica to that date by Khan et al.[4] We add to these cases already reported in the literature, with that our patient, to review a total of 31 cases (Tables 1–3). In this review, we conclude the features of sellar plasmacytoma with or without association with MM.

TABLE 1

Reports of Sellar Plasmacytoma Associated With Overt or Silent MM at Presentation

TABLE 3

Reports of Sellar Plasmacytoma without Development of MM on Follow-up

Incidence

Sellar mass is the third highest incidence of brain tumor, and pituitary adenoma occupies most of the lesion revolving the region. The presentation of plasmacytoma as a cranial or intracranial lesion is quite sparse, and it is even more rare a presentation that revolves the sella.[32] No instance that was reported in the series of Silverstein and Doniger[33] of 273 patients with MM regarded the sella turcica.

Pathology

The origin of sellar plasmacytoma may be the surrounding bone or the mucosa within the petrous or the sphenoid bone.[10] The electron microscopic study reveals the characteristic of extramedullary plasmacytoma is the parallel and convolutional r-ER in cytoplasm, and that may help to differentiate it from round-cell pituitary adenoma.[34]

Clinical Manifestation

In the series of the 31 cases mentioned above, the mean age was 56.7 years, ranging from 34 years to 75 years. The ratio between men and women was 15/16, it seems that sellar plasmacytomas with the development of MM on follow-up more likely happened in men than in women (men 6; women 3). Without the development of MM, sellar plasmacytomas seem to happen more often in women than in men (men 2; women 7); however, a high risk of developing MM or another isolated plasmacytoma was reported by Holland et al.[35] The chief complaints included headache (71.0%) and diplopia (61.3%) in most of the patients. Other complaints included visual loss or blurred vision (12.9%), ptosis (9.7%), facial pain or numbness (9.7%), and hearing loss (3.2%). The cranial nerves in most of the reported cases were affected (82.1%). The most commonly affected nerve was the abducens nerve (46.4%), followed by the oculomotor nerve (35.7%), the trochlear nerve (32.1%), the optic nerve (7.1%), and trigeminal nerve (7.1%). Some may manifest with multiple metastatic deposits and have an aggressive course.[4] The majority of the patients had intact anterior pituitary function, as in our own patient.

Classification

According to the report of Khan et al,[4] sellar plasmacytomas are divided into 3 categories: the first category includes patients with primary MM, who secondarily developed a plasmacytoma (Table 1); the second category includes patients who manifest with a sellar plasmacytoma initially and progress to MM on follow-up (Table 2); the third category includes patients who present with a solitary sellar plasmacytoma without evidence of MM (Table 3).

TABLE 2

Reports of Sellar Plasmacytoma With Development of MM on Follow-up

Diagnosis

Most cases were misdiagnosed preoperatively as the radiological appearance was undistinguishable from other pituitary masses. Even after surgery, some extreme rarity without systemic manifestations can lead to misdiagnosis.[20] The typical manifestation of sellar plasmacytomas include headache, cranial nerve palsy, and sellar bony destruction without gross anterior pituitary hormonal imbalance.[4,29] When the development of MM takes place, evidence of anemia, hypercalcemia, renal dysfunction, Bence-Jones proteinuria, plasma cell infiltration of the bone marrow biopsy, and positive serum protein electrophoresis detection may strengthen the diagnosis.

According to the subgroup of the Guidelines Working Group of the UK Myeloma Forum,[36] recommended diagnostic criteria for sellar solitary plasmacytoma are as follows: a single sellar mass of the clonal plasma cells; histologically normal marrow aspirates and trephine biopsies; normal results on skeletal surveys, including the radiology of long bones; anemia, hypercalcemia, or renal impairment due to plasma dyscrasia; and high-serum or urinary level of monoclonal immunoglobulins. When the last 2 points are taken together, it should be diagnosed as sellar plasmacytoma associated with MM.

Differentiation of the cause of a sellar mass is important because treatment and prognosis differ accordingly. The most common lesion of the sella remains pituitary adenoma. Other entities include gliomas, meningiomas, craniopharyngiomas, Rathke’s cleft cysts, epidermoids, chordomas, germ cell tumors, metastatic tumors, vascular lesions and granulomatous, and infectious or inflammatory processes.[37-39] Most sellar plasmacytomas mimic the clinical and radiological characteristics of pituitary adenoma and lead to misdiagnosis at admission. However, cranial nerve palsies occur at a later stage of the development of pituitary adenoma, which presents more often with pituitary hormone imbalance. On contrast, oculomotor impairments of sellar plasmacytoma present at the initial presentation, some isolated oculomotor symptoms progress rapidly, and sellar bony destructions with minimally disturbed anterior pituitary function are always revealed. Fukai et al[3] considered the lack of sellar enlargement, the lateral extension into the cavernous sinus, and the bony erosion differed from that of pituitary adenoma. Furthermore, total body exploration, with positron emission tomography, might be helpful for making a differential diagnosis. However, histopathological examination is required for a definitive diagnosis, especially the “gold standard method” of immunohistochemical analysis.[2]

Treatment

The most important step in the management of these patients is correct diagnosis. Transsphenoidal resection of the sellar mass should be made to establish the diagnosis and release the symptoms.[3] Once the diagnosis of sellar plasmacytoma is made, RT is the most common treatment.[5] And close follow-up and RT are the primary treatments designed to prevent the progression of solitary plasmacytoma to MM.[40,41] Once the diagnosis of sellar plasmacytoma with MM is made, systemic treatment must begin immediately. Prompt and appropriate RT and chemotherapy followed by APBSCT may improve the outcomes with a median survival of 5 years.[42] In these 31 cases, 92.4% of patients underwent RT either alone or with other modalities. Chemotherapy was administered to 57.7% of the patients. APBSCT was received by 15.4% of the patients, including our own patient.

Prognosis

Approximately 50% of plasmacytomas progress to overt MM in 10-year follow-up, and 10% of them recur with a plasmacytoma.[2] Recent studies using interphase fluorescent in-situ hybridization indicate that all MM cells harbor chromosome abnormalities.[43] Monosomy of chromosome 13, which presents in 85% of all MMs, is associated with an adverse prognosis.[44]

CONCLUSION

Sellar plasmacytomas with the development of MM on follow-up are more likely to happen in men than in women. If the sellar plasmacytoma does not compress the cranial nerve, transsphenoidal resection should be cautious, because the systemic treatment with RT, chemotherapy, and APBSCT may be more effective with little invasion.