Plasma cell tumor of the clivus: report of two cases

Transcription

1 Cir Cir 2012;80: Plasma cell tumor of the clivus: report of two cases Gerardo Guinto-Balanzar,* Miguel Abdo-Toro,* Norma Aréchiga-Ramos,** Roberto Leal-Ortega,** Erick Zepeda-Fernández,* and María de Jesús Nambo-Lucio*** Abstract Background: Plasma cell tumor only rarely affects the cranium and may be found as an isolated lesion or as part of multiple myeloma. In this review we present the clinical and radiological characteristics and analyze the evolution of two cases of this tumor located at the skull base, specifically in the clivus and sellar region. We also present a brief review of the literature. Clinical cases: Case #1: The patient was a 66-year-old female with a solitary plasmacytoma of the bone (the isolated form of plasma cell tumor) that was totally removed. Case #2: The patient was a 61-year-old male with the diffuse form of this disease who was submitted to subtotal removal. In both patients, adjuvant treatment based on radiotherapy and chemotherapy was proposed; however, only one patient (Case #2) accepted adjuvant treatment and had a very favorable result. Most clinical symptoms disappeared and the patient is currently alive and with a good quality of life (>3- year follow-up). The other patient (Case #1), despite the presence of the localized form of the disease, died 3 months after diagnosis. Conclusion: Early diagnosis and removal of as much of the tumor as possible, but mainly the opportune indication of adjuvant treatment with radiotherapy and chemotherapy, are the keys to management of these cases. Key words: clivus, plasma cell tumor, sellar region, skull base surgery, transsphenoidal surgery. Introduction Plasmacytomas are neoplasms characterized by monoclonal plasma cell proliferation and production of immunoglobulin G or A (commonly referred to as M protein). These lesions may present as solitary or diffuse. Extramedullary plasmacytoma (EP) and solitary bone plasmacytoma (SBP) together account for <10% of plasma tumors cells. 1 Multiple myeloma (MM) is a malignant diffuse proliferation of plasma cells and is considered to be the final stage in the progression of patients with EP and SBP. 2,3 * Neurocirugía, ** Neurología, Hospital de Especialidades, *** Hematología, Hospital de Oncología, Centro Médico Nacional Siglo XXI, México, D.F., Mexico Correspondence: Acad. Dr. Gerardo Guinto Balanzar Periférico Sur , Colonia Héroes de Padierna México, D.F., México Tel: (5255) gguinto@prodigy.net.mx Received for publication: Accepted for publication: EP is a vascularized soft tissue mass of submucosal origin without invasion to the bone marrow. It frequently affects the upper airways and sinuses (80%). It rarely appears at the skull base or the upper digestive tract and represents 1% of head and neck tumors. 4 SBP, also known as medullary plasmacytoma, is characterized by an isolated lytic lesion in the bone marrow in the absence of generalized plasmacytosis. The probability of progression to MM is different in these two varieties because it is three times more common in patients with SBP than with EP. 2,5 Plasmacytomas involving the skull are rare and most occur in the cranial vault. Only in rare cases (particularly in the SBP) does it affect the skull base and, when it does, it produces a variety of signs and symptoms often nonspecific which may cause a delay in diagnosis. 5,6 We present two cases of plasmacytomas at the skull base that were managed differently. Both patients underwent surgery. Gross total removal was achieved in one patient and, in the other patient, a partial removal. Unfortunately, one of the patients did not accept the proposed adjuvant management, which did allow us to analyze the natural history of the disease. The other patient responded favorably to adjuvant treatment. Currently, we do not know the existence of similar cases reported in Latin America. 162 Cirugía y Cirujanos

2 Plasma cell tumor of the clivus Clinical Cases Case 1 We present the case of a 66-year-old female with a clinical history of headache for 3 months characterized by oppressive bitemporal headache and diplopia. Physical examination revealed only paresis of the left VI cranial nerve. Cranial magnetic resonance imaging (MRI) with gadolinium showed the presence of a single lesion of ~ mm with invasion to the sellar region, upper clivus and sphenoid sinus (Figures 1 and 2). The remainder of the imaging studies showed no additional lesions in other bones. Complete transsphenoidal macroscopic resection of the lesion was done. Histopathological and immunohistochemical analyses revealed a plasma cell tumor (Figure 3). The patient was referred to the hematology oncology service for adjuvant treatment but refused chemotherapy and radiation treatments and died 3 months after surgery. Case 2 We present the case of a 61-year-old male with a clinical picture of 6 months evolution characterized by a moderately intensive progressive frontal headache associated with left pulsatile tinnitus. Four months later the patient developed a left temporal hemianopsia. Cranial computed tomography (CT) and MRI showed an infiltrating lesion located in the clivus and sellar region with invasion of both cavernous sinuses, and two lesions (one on each side) in the diploe of the parietal occipital region (Figures 4 and 5). A transsphenoidal subtotal resection of the lesion at the skull base was performed and histopathological analysis confirmed a plasma cell tumor. The patient underwent radiotherapy and chemotherapy. All symptoms improved after treatment and an MRI performed 3 years later showed a significant reduction in the size of the lesion in the clivus and sella turcica (Figure 6) as well as disappearance of the diploic lesions. At 3 years since diagnosis, the patient is alive with performance of usual daily activities. Discussion There are few reports of plasma cell tumors affecting the skull. Most of these tumors are located in the bones of the vault and only rarely affect the skull base. 1,4 In this study we present two cases of these tumors located in the clivus and the sella, which corresponds to EP (case 1) and cranial invasion form of MM (case 2). Figure 1. Axial cut MRI (T1 phase) with gadolinium that shows a lesion (arrow) that enhance homogeneously with contrast in the sellar region (case 1). Figure 2. Sagittal cut MRI (T1 phase) with gadolinium: tumor (arrow) invading the sellar region, sphenoid sinus and clivus (case 1). Plasma cell tumors of the skull base remain asymptomatic for a relatively long period of time. They tend to grow in clinically silent areas and, only when they reach a considerable size, cause symptoms mainly related to compression of cranial nerves and headaches. When located in the clivus (the joint of the occipital basilar apophysis and the sphenoid bone), the main symptom is diplopia due to compression of the VI cranial nerve, which has the longest path in this anatomic region. 1,4,6 Volume 80, No. 2, March-April

3 Guinto-Balanzar G et al. Figure 3. Histological examination (case 1) with light microscopy with hematoxylin and eosin showing infiltration of neoplastic plasma cells. Figure 5. Coronal cut MRI (T1 phase) with gadolinium: extra-axial tumor (arrow) in the sellar region with invasion of both cavernous sinuses (case 2). Figure 4. Sagittal cut MRI (T1 phase) with gadolinium: two lesions are shown that enhance homogeneously with gadolinium, one located in the sellar region with invasion of the sphenoid sinus and clivus and the other intradiploic located in the parietal region (arrows) (case 2). When plasmacytomas affect other regions of the skull base they may alter the function of other cranial nerves which, according to order of frequency, are II, V, VII and VIII.6,7 A rare case of compression of the posterior inferior cerebellar artery leading to a lateral medullary and bulbar syndrome characterized by dysphagia, vertigo, vomiting, paralysis of the soft palate, Horner syndrome, hypotonia, ataxia and sensitive dissociation has also been described.1,2,5 Plasma cell tumors affecting the skull base generally appear as a manifestation of MM. The presence of SBP is less common and represents <1% of all head and neck tumors.5 Figure 6. Control MRI (case 2). Shown is a decrease in lesion size in the sellar and clivus (arrow) and disappearance of the diploic lesion of the parietal dome 3 years after diagnosis. The main clinical manifestations of patients presented in this report were secondary to compression of cranial nerves (mainly II and VI), which is consistent with that reported in the literature. In none of our cases was the syndrome com- 164 Cirugía y Cirujanos

4 Plasma cell tumor of the clivus monly reported in MM found, namely, bone pain, anemia, renal failure and hypercalcemia. As a result, diagnosis was not suspected prior to surgery and both cases were operated with the possibility of being a chordoma of the clivus or an invasive pituitary adenoma. Radiological studies of plasmacytomas involving the skull base are not very specific. If located in the clivus and sellar region, the differential diagnosis of pituitary adenoma, clivus chordoma, lymphoma, metastatic adenoid cystic carcinoma, chondrosarcoma and osteosarcoma needs to be made. The presence of calcifications in the tumor may suggest the possibility of chondrosarcoma, osteosarcoma and chordoma. 8,9 On plain x-rays, plasmacytoma is usually seen as a lytic lesion with clear margins and a narrow transition zone to a nearly normal bone surrounding it. CT shows a welldemarcated tumor, occasionally with bone destruction and involvement of adjacent structures. On MRI it is demonstrated as an isointense lesion on T1 phase and moderate hyperintensity on T2 phase. These tumors generally show a significant homogeneous uptake with gadolinium. 8,9 Radiological findings mentioned were observed in our patients; however; as discussed previously, other tumors may have the same radiological characteristics. Because of this, and coupled with the rarity of this tumor at the skull base, in most cases the diagnosis is obtained through histopathology, as in the patients reported in this study. According to the diagnostic protocol of a plasma cell neoplasm, in addition to histopathological examination it is essential to have whole-body x-ray studies, serum and urine electrophoresis, complete blood count, serum calcium levels and bone marrow biopsy, all with a view to ruling out an association with MM. These studies were performed in our patients and, only in case 2, the association was confirmed. Treatment as well as prognosis are different in MM and SBP, hence the importance of establishing an accurate diagnosis. Treatment of these lesions includes complete surgical removal (within the margin of safety) in order to establish a diagnosis and to decompress the neural structures that may be affected and also to achieve tumor volume reduction. 10 Once the diagnosis has been established, the patient should be subjected to adjuvant management with radiotherapy and chemotherapy. 5,10,11 With regard to surgery, decompression of neural structures affected by the tumor in our patients resulted in clinical improvement, both in the visual field (after decompression of the optic nerves [case 2]) and the sixth cranial nerve paresis [case 1]). The main limitation of the removal of similar lesions lies in the invasion presented by difficult to access structures such as the cavernous sinus (case 2) where only a partial resection can be done. In general, these lesions are highly vascular, increasing the degree of difficulty of resection. The transsphenoidal approach, which can be assisted by endoscopy, 12 provides secure access to the sellar region and the upper and middle clivus, with low morbidity and mortality. In single lesions located within the cranial vault, excisional biopsy can be performed, whereas in multiple lesions fine needle aspirations can be done. 5,10,13 The differentiation between the isolated form of these tumors (SBP or EP) or the disseminated form of the disease (MM) is very important because the preferred treatment modality is surgery followed by radiation therapy, whereas for systemic MM chemotherapy is the preferred treatment. 7,10 Upon analyzing the cases presented in this report, it can be concluded that although surgery is helpful (especially in single lesions), it is not the main determinant prognostic factor. What actually determines prognosis is adjuvant therapy. In the particular case of these tumors infiltrating the skull base both as single lesions as in MM, treatment is based on the high radiosensitivity of these tumors where the recommended dose is Gy. 10,11 Treatment with chemotherapy consists of the administration of alkylating agents such as melphalan, cyclophosphamide or chlorambucil and prednisone administered 4 7 days every 4 6 weeks for 1 to 2 years. 2,14 The patient who underwent complete gross resection (case 1) had a more unfavorable course than the second patient where only subtotal resection was performed. The difference was that in the first case the patient refused adjuvant therapy. This fact demonstrates the aggressiveness of these lesions when left to their natural course. 10,11 It should be noted that although this case involved a localized form of plasma cell tumor and the patient underwent successful surgical removal, uncontrolled progression of the disease caused the death of the patient 3 months after diagnosis. In contrast, in case 2, although the patient had an advanced form of MM and the lesion was subtotally excised, adequate adjuvant treatment resulted in achieving highly satisfactory tumor control. Average survival of patients with MM is 3 years although there are other factors that may shorten survival including paraprotein load, renal failure, hypercalcemia, infiltration of plasma cells to other organs and development of pancytopenia refractory bone marrow cell treatment. 2,15 An estimated 15% of patients die within the first 3 months of diagnosis. The disease has a chronic evolution of 2 5 years before resulting in an acute terminal phase where the patient usually dies as a result of kidney failure and sepsis. 2 The prognosis for isolated forms is more benign: the probability of an EP progressing to MM is <30% with a 10-year disease-free period of 70%. In contrast, in SBP the likelihood of progression to MM is >50% with a 10-year disease-free period of only 16%. 1,2 Volume 80, No. 2, March-April

5 Guinto-Balanzar G et al. In conclusion, plasma cell tumors affecting the skull base rarely have nonspecific clinical and radiological findings. However, it must be considered in the differential diagnosis, especially when a lesion of the sella is associated with early involvement of cranial nerves. Not all apparently solitary plasma cell tumors of the skull base are isolated and can be the initial manifestation of MM. Clinical studies should be carried out even in the absence of radiological signs and symptoms. We recommend repeating the study after several months because of the high risk of progression from SBP to MM. In plasma cell tumors affecting the skull base, surgical removal of the tumor should be performed with margins as wide as possible, thereby reducing symptoms and establishing the diagnosis. However, patients should be subjected to radiotherapy and chemotherapy, which are the major factors for medium- and long-term disease control. References 1. Wein RO, Popat SR, Doerr TD, Dutcher PO. Plasma cell tumors of the skull base: four case reports and literature review. Skull Base 2002;12: Dimopoulas MA, Kiamouris C, Moulopoulos LA. Solitary plasmacytoma of bone and extramedullary plasmacytoma. Hematol Oncol Clin North Am 1999;13: Munshi NC, Tricot F, Barlogie B. Plasma cell neoplasms. In: De- Vita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, 6th ed. Philadelphia: Lippincott Williams & Wilkins: pp Mahale A, Ullal S, Thiagarajan D, Das S. Plasmacytoma of the base of skull A case report. Indian J Med Paediatric Oncol 2007;28: Ustuner Z, Basaran M, Kiris T, Bilgic B, Sencer S, Sakar B, et al. Skull base plasmacytoma in a patient with light chain myeloma. Skull Base 2003;13: Montalban C, Martin-Aresti J, Patier JL, Martínez-San Millan J, García-Cosio M. Intracranial plasmacytoma with cranial nerve neuropathy in multiple myeloma. J Clin Oncol 2005;23: Meyer JR, Roychowdhury S, Cybulski G, Russell EJ. Solitary intramedullary plasmacytoma of the skull base mimicking aggressive meningioma. Skull Base Surg 1997;7: Pancholi A, Raniga S, Vohra PA, Vaidya V, Prajapati A, Mansingani S. Imaging features of extramedullary plasmacytoma of skull base with multiple myeloma A rare case. Ind J Radiol Imag 2006;16: Vogl TJ, Steger W, Grevers G, Balzer J, Mack M, Felix R. MR characteristics of primary extramedullary plasmacytoma in the head and neck. Am J Neuroradiol 1996;17: Bindal AK, Bindal RK, van Loveren H, Sawaya R. Management of intracranial plasmacytoma. J Neurosurg 1995;83: Gil Z, Cohen J, Spektor S, Leider-Trejo L, Fliss D, Beasley N, et al. Recurrent anterior skull base plasmocytoma. Skull Base 2002;12: Park SH, Kim YZ, Lee EH, Kim KH. Endoscopic endonasal transsphenoidal resection of solitary extramedullary plasmacytoma in the sphenoid sinus with destruction of skull base. J Korean Neurosurg Soc 2009;46: Singh AD, Chacko AG, Chacko G, Rajshkhar V. Plasma cell tumors of the skull. Surg Neurol 2005;64: Yamaguchi S, Terasaka S, Ando S, Shinohara T, Iwasaki Y. Neoadjuvant therapy in a patient with clival plasmacytoma associated with multiple myeloma: a case report. Surg Neurol 2008;70: Susnerwala SS, Shanks JH, Banerjee SS, Scarffe JH, Farrington WT, Slevin NJ. Extramedullary plasmacytoma of the head and neck region: clinicopathological correlation in 25 cases. Br J Cancer 1997;75: Cirugía y Cirujanos