CASE REPORT
Primary Malignant Melanoma of the Sphenoid Sinus as a Crucial Differential Diagnosis of Skull Base Tumors: A Case Report
2025 年 12 巻 p. 189-195
詳細
2025 年 12 巻 p. 189-195
A 79-year-old man presented with progressive ptosis, diplopia, and headaches, which led to the diagnosis of a rare primary malignant melanoma of the sphenoid sinus. Imaging revealed extensive bone destruction and aggressive tumor behavior. The rarity of primary malignant melanoma in the sphenoid sinus complicates early detection. Despite undergoing surgical decompression, immunotherapy, and radiation therapy, the tumor rapidly recurred, necessitating supportive care. This case highlights the need for neurosurgeons to include primary malignant melanoma in the differential diagnosis of skull base tumors, particularly in the sphenoid sinus, due to its potential for aggressive local invasion and significant impact on critical neurovascular structures. Early recognition and intervention are crucial for managing this rare and aggressive malignancy effectively.
Primary malignant melanoma of the sphenoid sinus is an extremely rare condition, with less than 15 cases reported since 1986. Its nonspecific initial symptoms, such as headaches and diplopia, often lead to a delayed diagnosis. However, the disease can progress rapidly, causing severe visual deficits and functional decline.1,2) The prognosis largely depends on early detection and the extent of surgical resection, although complete removal is challenging due to the tumor's proximity to critical structures. Given its resistance to radiotherapy, early surgical intervention is crucial.1,2) This case report contributes to the limited body of knowledge, highlighting the need for early recognition of tumors near the sella turcica.
A 79-year-old man with no prior history of tumorous lesions presented with left ptosis as the initial symptom. Ten days later, he developed diplopia, which was followed by the onset of headache and vomiting 4 days later, leading to hospitalization at a local hospital. Imaging studies, including X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), revealed a tumorous lesion extending from the sphenoid sinus with significant bone destruction affecting the sella turcica and clivus. The lesion demonstrated strong contrast enhancement (Fig. 1).
Preoperative imaging.
Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) images are presented. Image A is T1-weighted (T1WI), B is T2-weighted (T2WI), and C-E are T1-weighted with gadolinium contrast (T1-Gd) in axial, coronal, and sagittal images. The tumor shows isointensity on T1WI and slightly low intensity on T2WI. It forms lobulations while filling the sphenoid sinus and extends to the sella turcica and clivus. The tumor demonstrates heterogeneous contrast enhancement, with areas in the posterior portion appearing cystic, showing isointensity on both T1 and T2 but with enhancement. Image F is non-contrast CT, G is contrast-enhanced CT, and H is the bone window. The isodense tumor fills the sphenoid sinus, with minimal residual bone at the base of the sella. However, parts of the anterior wall of the sphenoid sinus and the posterior clinoid process are destroyed, and the cortical bone of the clivus is significantly thinned.
Three weeks after the onset, the patient developed bilateral ptosis, with preserved pupillary light reflexes in both eyes, yet experienced a nearly complete loss of voluntary eye movements, resulting in functional blindness. laboratory evaluation of the hypothalamic-pituitary axis revealed partial hypopituitarism, indicated by the following values: free T3 at 1.84 pg/mL (normal range: 2.4-4.0 pg/mL), thyroid-stimulating hormone at 0.09 mIU/L (normal range: 0.610-4.230 mIU/L), and prolactin at 30.6 ng/mL (normal range: <15.0 ng/mL).
One month after the onset of symptoms, the patient became unable to eat due to persistent headaches and repeated vomiting. Suspecting metastasis to the pituitary gland or sphenoid sinus from a malignant tumor, lymphoma, or chordoma, an endonasal surgical approach was performed. Intraoperatively, the tumor was highly vascularized and predominantly composed of dark, hemorrhagic tissue suggestive of intratumoral hematoma (Fig. 2).
Intraoperative findings.
Intraoperative images are presented. The incised mucosa of the sphenoid sinus was highly vascularized and prone to bleeding. The anterior wall of the sphenoid sinus could not be identified, and a highly vascular, hemorrhagic tumor was found beneath the mucosa. The tumor was friable and dark in color, resembling a blood clot during surgery.
The anterior wall of the sphenoid sinus was destroyed and could not be identified. Two samples were sent for intraoperative rapid pathology, both of which suggested lymphoma. Therefore, the surgery was limited to mild tumor decompression. Postoperatively, there was a temporary, mild improvement in ocular movement, and the headache and nausea subsided, allowing oral intake. However, within 2 weeks, the patient experienced a recurrence of headache and nausea, and imaging revealed rapid regrowth of the tumor, filling the resection cavity (Fig. 3).
Postoperative imaging.
Postoperative images are shown. A-C: The contrast-enhanced magnetic resonance imaging (MRI) taken on postoperative day 3 shows decompression of the tumor cavity, with communication established between the cystic component posterior to the tumor. D-F: The contrast-enhanced MRI taken on postoperative day 28 shows that the resection cavity has been replaced by fluid accumulation, and rapid tumor growth has led to nasal cavity obstruction.
Permanent histopathology revealed diffuse proliferation of large atypical cells with a high nucleus-to-cytoplasm ratio against a background of fibrotic nasal or paranasal sinus mucosa. Some atypical cells exhibited nuclear pleomorphism, with melanin deposits in both the cytoplasm and stroma. Numerous mitotic figures and apoptotic bodies were observed, consistent with a small round-cell tumor (Fig. 4A). The atypical cells were positive for S-100 and HMB-45 (Fig. 4B and C), negative for cytokeratin (AE1/AE3) and leukocyte common antigen (CD45), and retained integrase interactor 1 staining; BRAF p.V600E was negative (not shown).
Histopathological findings.
Histopathological findings are presented. A: Large atypical cells with a high nucleus-to-cytoplasm (N/C) ratio show diffuse proliferation, with some cells exhibiting nuclear pleomorphism. Melanin is observed within the cytoplasm and stroma. Numerous mitotic figures and apoptotic bodies are present.
B, C: The atypical cells are positive for S-100 protein and HMB-45 markers in immunohistochemistry.
Based on these findings, a diagnosis of malignant melanoma was made. Whole-body examination, including upper and lower endoscopy and whole-body positron emission tomography-CT, ruled out a primary lesion in the trunk, leading to a diagnosis of primary malignant melanoma of the sphenoid sinus. Although a second surgery for maximal tumor resection was considered, the dermatology-oncology team advised against it, and the patient was transferred to a specialized hospital for chemotherapy with immune checkpoint inhibitors, molecular targeted therapy, and radiotherapy. Despite these efforts, the disease continued to progress, and the patient is currently receiving the best supportive care 4 months postoperatively.
Melanoma is an aggressive malignancy arising from melanocytes, typically found in the skin, mucosal surfaces, and eyes. It is characterized by rapid progression and a high potential for metastasis.1) Advances in immunotherapy and targeted treatments have improved outcomes for some subtypes, but treatment resistance and poor prognosis remain significant challenges, particularly in rare forms such as mucosal melanoma.2) Specific genetic abnormalities in malignant melanoma are known to be associated with treatment resistance and poor prognosis. NRAS mutations are linked to aggressive disease and limited responses to immune checkpoint inhibitors.3) Similarly, KIT mutations, frequently observed in mucosal melanomas, exhibit resistance to radiotherapy and variable responses to molecularly targeted therapies.4) Furthermore, CCND1 amplifications and CDKN2A deletions, commonly found in mucosal melanomas, complicate treatment strategies.5) These findings highlight the critical role of genetic profiling in guiding therapeutic decisions. Malignant melanoma is predominantly a disease of the skin and mucosa, with primary sinonasal melanomas accounting for only 0.5%-1.5% of all cases.6) Among these, primary melanomas originating in the sphenoid sinus are extremely rare, with only 11 cases reported in the literature since the first case was described by Carter et al. in 1986.6-17) This case represents the 12th reported instance. In addition to our report, we have reviewed previous case reports to summarize the initial symptoms, treatment approaches, and outcomes (Table 1).
| No. | Sex | Age | Ethnicity | Initial symptoms | Range of progress | Period to definitive diagnosis | Symptoms before surgery | Treatment | Outcome | Year |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 67 | White | Nasal stuffiness, epistaxis | N/A | 2.5 year | Nasal stuffiness, epistaxis | Excision, radiation therapy | Alive at 2.5 year | Carter et al., 1986 |
| 2 | F | 67 | N/A | Diplopia, right lacrimation, vision impairment of right eye | Sella turcica | Autopsy case | Diplopia, right lacrimation, headache, V1 trigeminal neuralgia, ptosis, bilateral visual disturbance | Radiation therapy |
Died 3 months later | Shinbori et al., 1988 |
| 3 | F | 87 | N/A | Headache, diplopia | Optic canal, cavernous sinus, middle fossa | 2 months | Headache, diplopia, dysopia | Biopsy, primary photon-beam external radiation (46 Gy) | Died 1 year later | Busaba et al., 2000 |
| 4 | F | 83 | Japanese | Headache | Sella turcica | 4 months | Headache, nasal bleeding, anosmia, dysopia, anisocoria, median fixation of the eyeball, partial hypopituitarism | Surgery | Died 6 Months later | Asano et al., 2000 |
| 5 | M | 56 | Spanish | Headache | Cavernous sinus | Several months | Headache, diplopia, ptosis | Biopsy, radiotherapy (70 Gy) | Alive at 4 years | Pino Rivero et al., 2004 |
| 6 | F | 83 | N/A | N/A | Cavernous sinus | Several weeks | Trigeminal paresthesia, ptosis, diplopia | Surgery, radiation therapy (60 Gy) | Alive 15 months after presentation | Lynch et al., 2005 |
| 7 | M | 75 | Black | N/A | Cavernous sinus, middle fossa | Several weeks | Headache, diplopia, ptosis | Biopsy, radiation therapy, chemotherapy | N/A | Batra et al., 2005 |
| 8 | F | 74 | N/A | Visual disturbance of the left eye | Sphenoid sinus, ethmoid sinus, left middle fossa | N/A | Bilateral visual disturbance, headache, ophthalmalgia, paresis of cranial nerveIII | Biopsy | Died 3 months later | Tsukahara et al., 2013 |
| 9 | M | 70 | N/A | N/A | Nasal septum, sella turcica | Several weeks | Headache, light-headedness, lassitude, bilateral blurry vision, diplopia, tonic seizure | Surgery, radiation therapy, chemotherapy | Died 7 months later | Smith SM et al., 2015 |
| 10 | M | 57 | N/A | N/A | Left side of ethmoidal sinus, left optic foramen | Several weeks | Nasal congestion, epistaxis | Surgery, radiation therapy (60 Gy), chemotherapy, immunotherapy, interferon therapy | Died 1 year later | Zhao et al., 2015 |
| 11 | F | 50 | N/A | N/A | Right side of sphenoid sinus | 2 months | Headache, epistaxis | Surgery, radiation therapy (70 Gy), Chemotherapy | Alive 10 months after presentation | Mandal et al., 2022 |
| 12 | M | 57 | N/A | N/A | Right side of cavernous sinus, clivus, sella turcica | 2 months | Headache, trigeminal paresthesia, ptosis | Surgery, radiation therapy (60 Gy) | Died 2 years later | Liu et al., 2024 |
| 13 | M | 79 | Japanese | Left ptosis | Sella turcica, clivus | 1 month | Left ptosis, headache, nausea, partial hypopituitarism bilateral oculomotor paresis, visual disturbance | Surgery, radiation therapy, immunotherapy | Alive 4 months after presentation | Present case |
| F: female; M: male; N/A: not applicable; No., number | ||||||||||
The symptoms of primary sphenoid sinus malignant melanoma often begin with nonspecific signs such as headache, nasal obstruction, and epistaxis, making early detection challenging. As the disease progresses, patients may rapidly develop symptoms resembling orbital apex syndrome, including visual field deficits, diplopia, facial pain, and ptosis. The prognosis of malignant melanoma is closely associated with the extent of the primary lesion, the completeness of surgical resection, and the occurrence of distant metastases. Early and appropriate surgical intervention is crucial for symptom relief and improving prognosis.11)
Reports of primary malignant melanoma of the sella turcica,18) metastatic melanoma to the pituitary gland,19) and metastatic melanoma to pituitary adenomas20) highlight the increasing prevalence of endonasal surgeries. Reporting such rare cases of malignant melanoma in this region is significant for expanding the knowledge of neurosurgeons and for considering the still undefined treatment strategies.11,21) Mucosal-origin melanoma is known to be resistant to radiotherapy and follows an aggressive course among sinonasal tumors.22) Given the involvement of critical structures such as cranial nerves and the internal carotid artery within the cavernous sinus and the favorable outcomes of stereotactic radiotherapy for intracranial melanoma,18) it is imperative to continue accumulating case reports of melanoma in the skull base region.
Primary malignant melanoma in the sphenoid sinus is an uncommon and challenging condition. Although case reports are gradually expanding our understanding, it remains a diagnosis that neurosurgeons should consider, especially in patients presenting with symptoms like headaches or double vision. Due to the rapid progression of symptoms, which can significantly impact daily living, it is important to include this rare disease in the differential diagnosis of sella turcica-related tumors requiring timely treatment.
Involving an otolaryngologist is highly recommended in such scenarios, as their expertise can aid in early and precise diagnosis, particularly when the disease has progressed. In this case, the tumor was thought to originate within the sella turcica, so only neurosurgical intervention was performed. However, reflecting on the situation, seeking input from an otolaryngologist could have provided a more thorough evaluation and treatment plan. Endoscopic assessments by an otolaryngologist may have identified potential sinonasal involvement, contributing to more targeted imaging and biopsy efforts. This interdisciplinary approach can enhance diagnostic accuracy, expedite intervention, and improve overall patient outcomes.
A written informed consent form was provided by the patient for the use of the data for the present manuscript.
Author Takakazu Kawamata is one of the Editorial Board members of the Journal. This author was not involved in the peer-review or decision-making process for this paper.
There are no conflicts of interest.
