Multicentric giant cell tumor: metachronous central and peripheral involvement.
Giant cell tumors are rare in the head and neck region. The most frequently involved sites of giant cell lesions in the head and neck are the maxilla and mandible, whereas the sphenoid and temporal bones are rarely involved. This tumor is usually located in the long bones of limbs. Reparative granuloma and brown tumor of hyperparathyroidism must be included in the differential diagnosis. Here we report the clinical and radiologic findings of a multicentric giant cell tumor with skull base involvement in a female patient. This case report demonstrates the similar pathophysiology of peripheral and central giant cell tumors.
Giant cell tumor (GCT) was first described in 1953 as a reactive lesion to an intraosseous hemorrhage following trauma to the jaw. (1) It is rare in the head and neck region and is reported as 0.00011% in a population-based, retrospective study. (2) In more than 60% of cases, the tumor is seen in female patients, and it is more prevalent in patients less than 30 years of age. (3,4) Central GCTs, although rare, are challenging for head and neck surgeons because of a high recurrence rate, potential metastases, and the difficulty of total removal. (3)
Peripheral and central GCTs have some differences. For example, peripheral tumors are associated with a higher age of occurrence, and they arise from the soft tissue outside the cortex. (5) It is important to note, however, that both types of GCTs have a similar cellular phenotype, and there is no significant difference in histology. Therefore, similar pathophysiology has been assumed. (5)
Here we describe a multicenteric GCT in a female patient, a finding that demonstrates the similar pathophysiology of peripheral and central GCTs.
A 30-year-old woman with a known case of recurrent peripheral GCT was referred to our otolaryngology clinic because of progressive right-sided nasal obstruction. She had a history of recurrent GCTs of the limbs. Her problem had begun 11 years earlier with pain in her right wrist. Histopathologic examination of the osteolytic lesion showed a bone tumor with vascular stroma, spindle-shaped stromal cells, and multinucleated giant cells, demonstrating GCT of the right radius.
By the time we saw the patient, she had experienced multiple recurrences and had undergone four surgeries on her right hand. The pathologic examinations of the surgically obtained specimens were all in favor of GCT except one that was interpreted as an aneurysmal bone cyst because of the presence of vascular spaces and osteoclastic granuloma. However, in the subsequent recurrence, GCT was again pathologically confirmed, and reexamination of the previous pathologic specimen showed that a misdiagnosis had occurred.
The patient also had shoulder involvement and a huge (9 x 2 cm) tumor with erosion of the head, neck, and diaphysis of the left humerus seen on x-rays. This histopathologically confirmed metachronous GCT recurred twice, and because the glenohumeral joint was involved, the joint was replaced with a prosthesis. She had also developed a sacral tumor on the right side (5 x 4 cm) involving the intrapelvic region, spinal canal, and sacral nerve root. The tumor had been managed with angiography/embolization, surgical debulking, and adjuvant regional radiotherapy.
Our patient lived in the city of Mashhad (in the northeast of Iran), was married, had a normal pregnancy and labor when she was 21 years of age, and no significant medical history other than GCT. She did not smoke cigarettes or drink alcohol. Her family history was negative for GCT.
The patient underwent a thorough physical examination (i.e., head, neck, and systemic). Multiple scars on her right wrist and left shoulder were apparent. On rhinoscopy and nasal endoscopy, a submucosal bulging on the left side of the nasopharynx and sphenoid sinus was seen. Other head and neck structures including her eyes and ears were found to be normal. The serum concentrations of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 24-hour urine calcium and phosphorus were all within the normal range. Parathyroid scintigraphy was also normal.
On computed tomography (CT) with intravenous contrast, a large, soft-tissue nasopharyngeal mass with extension into and erosion of the sphenoid sinus walls, pterygoid plates, and sella turcica and protrusion into the middle cranial fossa was found (figures 1 and 2). The infraorbital fissure was involved on the right side.
Complete resection was impossible because of the involvement of the skull base and cavernous sinus. The patient underwent tumor debulking by endoscopic sinus surgery, and after histopathologic confirmation of GCT, she received radiotherapy. At the 14-month follow-up, there had been no recurrence.
[FIGURE 1 OMITTED]
The head and neck region is a rare site for a GCT (2% of all GCTs). (6,7) The most frequently involved sites of giant cell lesions in the head and neck are the maxilla and mandible, whereas the sphenoid and temporal bones are rarely involved. (8) The higher prevalence of giant cell lesions in the maxilla and mandible may be due to a higher prevalence of trauma to these regions. In our patient with multicentric GCT, who showed systemic involvement, the maxilla and mandible were intact--a finding that is incompatible with previous reports. The reason this tumor is more prevalent in females in their third decade of life has not yet been established. (5)
This tumor usually appears in imaging studies as a well-circumscribed, lytic lesion surrounded by little or no sclerosis. It may break through the cortex and invade the soft tissue. In our patient, although the sphenoid sinus wall was thinned by the tumor, it did not break through the intracranial fossa.
Aneurysmal bone cyst, chondroblastoma, dermoid cyst, chondrosarcoma, giant cell reparative granuloma, and pigmented villonodular synovitis are the most important entities that should be included in the radiologic differential diagnosis. (7,9) These cannot be differentiated radiologically, so histologic examination is the best way to make a diagnosis. Nevertheless, histopathologic studies sometimes may be misleading, as in our case, when one of the pathologic specimens was mistakenly identified as an aneurysmal bone cyst rather than a GCT. Giant-cell-containing lesions of the jaw that can be mistaken for each other histologically include GCT, giant cell granuloma, cherubism, and fibrous dysplasia of the jaw. (10,11) Therefore, this tumor requires a high index of clinical suspicion, and obtaining a histologic diagnosis may be extremely difficult when the tumor has atypical features.
No single histopathologic finding predicts aggressive behavior, and metastasis has been reported in tumors with a bland morphology. (12) Increased mitotic figures (20 or more per high-power field), necrosis, monomorphism, spindling of cells, abundant eosinophilic cytoplasm, and large nuclei with nucleoli and myxoid stroma may suggest a worse clinical outcome. (13) However, the clinical course is the determining factor for aggressiveness and malignant behavior.
GCT has a high recurrence rate, which may be related to the type of treatment: It recurs in 30 to 50% of patients treated solely by an intralesional surgical approach and in 8% with marginal therapy. (14) Our case emphasizes the high failure rate of local resection of tumor. Other treatment modalities such as radiotherapy and adjuvant chemotherapy can be considered when complete surgical excision may cause unacceptable functional deficits; however, malignant sarcomatoid transformation in rare cases can be a major problem. (15,16)
[FIGURE 2 OMITTED]
Systemic treatments such as calcitonin and interferon have been proposed. Calcitonin was administered to our patient with no success, however. Recurrent GCTs are assumed to carry a higher risk for malignancy than primary ones. (16)
In summary, the case presented in this article involved a multicentric GCT arising in an upper limb, the sacrum, and the sphenoid sinus. This tumor has not been previously described at these sites of involvement and distribution. This case demonstrates the similar pathophysiologic characteristics of peripheral and central GCTs. In these cases, systemic treatments such as interferon or calcitonin may be a better choice than surgical excision, (17) although further study is needed to prove their efficacy.
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From the Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran.
Corresponding author: Amir A. Sazgar, MD, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Imam Khomeini Medical Complex, Dr. Gharib Ave., Keshavarz Blvd., Tehran, Iran. Email: email@example.com