Tumor-to-tumor metastasis of small cell carcinoma of presumed pulmonary origin to a sphenoid ridge meningioma: A diagnostic pitfall in preoperative systemic evaluation

Abstract

Background:

Tumor-to-tumor metastasis (TTM) to a meningioma is rare. Atypical meningioma-like lesion with systemic cancer risk factors warrants evaluation for metastatic disease before resection.

Case Description:

An 80-year-old man with a smoking history and pulmonary emphysema presented with progressive cognitive decline. Magnetic resonance imaging showed a rapidly enlarging left sphenoid ridge dural-based mass with heterogeneous enhancement and extensive peritumoral edema. Chest radiography revealed a right upper paramediastinal opacity, but chest computed tomography and systemic staging were not performed before craniotomy. Histopathology demonstrated metastatic small cell carcinoma within a meningothelial meningioma, confirming TTM. Postoperative imaging supported small cell carcinoma of presumed pulmonary origin. Despite radiotherapy and chemotherapy, leptomeningeal dissemination developed, and the patient died 15 months after surgery.

Conclusion:

In older smokers with abnormal chest radiograph and atypical meningioma-like lesions, systemic malignancy should be evaluated before resection. When surgery is necessary, the operative goal should prioritize tissue diagnosis and decompression.

INTRODUCTION

Tumor-to-tumor metastasis (TTM) is defined as true metastatic growth of one neoplasm within a histologically distinct recipient neoplasm.[2,17] Meningiomas are among the most common intracranial recipient tumors, and breast and lung cancers are frequent donor malignancies.[6,10-12,14,19] However, metastasis of small cell carcinoma to a meningioma is exceptionally rare, with only a few cases reported.[1,3,5,7,9]

Preoperative recognition of TTM is challenging because dural metastases and metastatic components within meningiomas may mimic conventional meningiomas. Rapid interval growth, heterogeneous enhancement, disproportionate peritumoral edema, intratumoral hemorrhage or necrosis, and systemic cancer risk factors should prompt reconsideration of the preoperative diagnostic pathway and evaluation for an underlying malignancy.[1,4,5,9,13] Recognition of possible metastatic disease before surgery may influence systemic staging, prognostic assessment, multidisciplinary treatment planning, and the objectives and extent of neurosurgical intervention.

We report this case to highlight the importance of integrating atypical intracranial imaging findings with systemic cancer clues when evaluating and planning treatment for presumed meningioma.

CASE PRESENTATION

In February 2024, an 80-year-old man was referred to our department due to progressive cognitive decline. Brain magnetic resonance imaging (MRI) at a local clinic approximately 7 months earlier had demonstrated an extra-axial tumor arising from the left sphenoid ridge and measuring 25 × 21 mm in maximum axial dimensions [Figure 1a]. Follow-up MRI demonstrated enlargement of the lesion to 38 × 31 mm [Figure 1b]. Contrast-enhanced T1-weighted imaging showed heterogeneous enhancement, including a focal intratumoral area with an enhancement pattern distinct from that of the surrounding tumor [Figure 1c]. He was referred to our department for further evaluation and treatment.

Figure 1:

Serial preoperative neuroimaging and angiographic findings. (a) Initial fluid-attenuated inversion recovery (FLAIR) magnetic resonance image (MRI) obtained at a local clinic shows a left sphenoid ridge extra-axial mass measuring 25 × 21 mm in maximum axial dimensions (white arrow), with peritumoral edema (white arrowhead). (b) Follow-up FLAIR MRI obtained 7 months later shows enlargement of the mass to 38 × 31 mm in maximum axial dimensions (white arrow), accompanied by increased peritumoral edema (white arrowhead). (c) Contrast-enhanced T1-weighted MRI shows heterogeneous enhancement of the tumor (white arrow), including a focal intratumoral area with an enhancement pattern distinct from that of the surrounding tumor (white arrowhead). (d) FLAIR MRI obtained on admission shows extensive peritumoral edema involving the adjacent left frontal and temporal lobes (white arrow). (e and f) Axial and coronal contrast-enhanced T1-weighted MRI obtained on admission show a 46 × 33 × 33 mm dural-based mass centered on the left sphenoid ridge, with heterogeneous but predominantly strong enhancement (white arrows). (g and h) Digital subtraction angiography shows tumor blush in the left sphenoid ridge region (white arrow). The rapid interval growth, extensive peritumoral edema, and heterogeneous enhancement raised concern for high-grade meningioma, dural metastasis, or a meningioma harboring a metastatic component.

On admission, his Glasgow Coma Scale score was 14 (E4V4M6). He was able to state his name and date of birth but was disoriented to place. He had no aphasia, headache, seizures, visual disturbance, diplopia, facial sensory disturbance, dysphagia, other cranial nerve deficits, motor weakness, or sensory deficits. His medical history included pulmonary emphysema and hypertension. He was a former smoker with a 38-pack-year history, having smoked 20 cigarettes/day from 20 to 58 years of age and quit smoking 22 years before presentation. He reported no cough, sputum production, hemoptysis, dyspnea, weight loss, or loss of appetite.

MRI performed on admission demonstrated a 46 × 33 × 33 mm dural-based extra-axial mass centered on the left sphenoid ridge [Figure 1d-f]. Although the lesion had a meningioma-like appearance, it showed several features atypical for a conventional benign meningioma: rapid interval growth, heterogeneous enhancement with a focal intratumoral area showing an enhancement pattern distinct from that of the surrounding tumor, and extensive peritumoral edema involving the adjacent left frontal and temporal lobes. Digital subtraction angiography demonstrated tumor blush in the left sphenoid ridge region [Figure 1g and h]. The preoperative differential diagnosis included high-grade meningioma, solitary fibrous tumor, dural metastasis, and a meningioma harboring a metastatic component.

Preoperative chest radiography demonstrated an abnormal opacity in the right upper paramediastinal region [Figure 2a]. This abnormality was not further characterized before surgery. Neither chest computed tomography (CT), positron emission tomography-CT, nor serum tumor marker testing was performed, and the operation proceeded without systemic staging despite the inclusion of metastatic disease in the differential diagnosis. Despite the unresolved possibility of metastatic disease and the absence of systemic staging, craniotomy and maximal safe resection were undertaken because of progressive cognitive decline, interval tumor enlargement, and extensive peritumoral edema.

Figure 2:

Thoracic and systemic imaging findings before and after craniotomy. (a) Preoperative upright chest radiograph shows an abnormal opacity in the right upper paramediastinal region (black arrow). This finding was not further evaluated with chest CT before craniotomy. (b) Postoperative axial contrast-enhanced chest CT obtained with mediastinal window settings demonstrates a central right upper-lobe lesion obstructing the right upper-lobe bronchus (white arrow), with enlarged mediastinal lymph nodes consistent with cN2 disease (white arrowheads). Because the lesion was confluent with adjacent post obstructive atelectasis, its margins could not be reliably delineated for separate size measurement. (c) The corresponding axial CT image obtained with lung-window settings shows the central lesion and associated right upper-lobe atelectasis (white arrow). (d) Coronal lung-window CT further demonstrates the craniocaudal extent of the combined lesion-atelectasis complex (white arrow). (e) Postoperative contrast-enhanced abdominal CT shows a 15 × 12 mm hypoattenuating lesion in the pancreatic-tail, clinically considered to represent pancreatic metastasis (white arrow). Together with the histopathological identification of metastatic small cell carcinoma within the resected intracranial tumor, these thoracic and systemic imaging findings supported a clinical diagnosis of small cell carcinoma of presumed right upper-lobe pulmonary origin, staged as cTxN2M1c (stage IVB).

A left pterional craniotomy was performed with drilling of the sphenoid ridge and temporal base. After dural opening, the tumor was found to protrude from the Sylvian fissure. Grossly, the lesion was heterogeneous, with very soft and highly hemorrhagic areas admixed with firm fibrous components. The initial frozen-section specimen was nondiagnostic; an additional specimen raised suspicion for metastatic carcinoma but did not provide a definitive diagnosis.

The Sylvian fissure was opened to delineate the tumor-brain interface. The tumor was densely adherent to the adjacent arachnoid and brain surface, and a clear dissection plane was absent along portions of the temporal and frontal bases. Piecemeal internal decompression was performed, followed by controlled aspiration with a Cavitron Ultrasonic Surgical Aspirator after partial mobilization. The cistern was opened, and the optic nerve was identified. At the superior aspect of the lesion, the tumor-brain interface was indistinct. Because perforating branches of the left middle cerebral artery were considered to be at risk, further aggressive dissection was avoided. Maximal safe subtotal resection was completed, leaving a small residual capsular component. Postoperative chest CT demonstrated a central right upper lobe lesion obstructing the right upper-lobe bronchus, with post obstructive atelectasis [Figure 2b-d]. Because the lesion was confluent with the atelectatic lung, its margins could not be reliably delineated for separate size measurement. Enlarged mediastinal lymph nodes were consistent with cN2 disease. Abdominal CT showed a 15 × 12 mm hypoattenuating pancreatic-tail lesion considered metastatic [Figure 2e].

Histopathological examination demonstrated two intermingled tumor components [Figure 3a and b]. The recipient tumor consisted of bland meningothelial cells with a whorled architecture and a Ki–67 labeling index of <1%. The second tumor component, intermingled within the meningioma, consisted of densely proliferating small atypical cells with scant cytoplasm, hyperchromatic nuclei, and a high nuclear-to-cytoplasmic ratio. The metastatic cells were positive for synaptophysin [Figure 3c], showed nuclear positivity for INSM1 [Figure 3d], were focally positive for chromogranin A, and had a markedly high Ki-67 labeling index [Figure 3e]. The meningioma component showed nuclear positivity for progesterone receptor [Figure 3f]. These findings established a diagnosis of metastatic small cell carcinoma within a meningothelial meningioma, consistent with TTM.

Figure 3:

Histopathological and immunohistochemical findings of tumor-to-tumor metastasis. (a) Hematoxylin and eosin staining at ×40 magnification shows two intermingled tumor components within the same lesion: Relatively pale meningothelial meningioma tissue with a whorled architecture (arrow) and densely cellular nests of metastatic small cell carcinoma (arrowheads). (b) Hematoxylin and eosin staining at ×100 magnification shows small atypical cells with a high nuclear-to-cytoplasmic ratio and hyperchromatic nuclei, consistent with metastatic small cell carcinoma (arrowheads), admixed with bland eosinophilic meningothelial tumor cells (arrow). (c) The metastatic small cell carcinoma component shows cytoplasmic positivity for synaptophysin (arrowheads), whereas the adjacent meningothelial component is negative (arrow). (d) The metastatic component shows nuclear positivity for INSM1 (arrowheads), whereas the adjacent meningioma component is negative (arrow). (e) Ki-67 immunostaining demonstrates a markedly high labeling index in the metastatic small cell carcinoma component (arrowheads), whereas the meningioma component shows a low labeling index (arrow). (f) The meningothelial meningioma component shows nuclear positivity for progesterone receptor (arrow), whereas the metastatic small cell carcinoma component is negative (arrowheads). Taken together, these findings support the diagnosis of metastatic small cell carcinoma within a meningothelial meningioma, consistent with tumor-to-tumor metastasis. Scale bars = 500 μm in (a) and 200 μm in (b-f).

Early postoperative contrast-enhanced MRI demonstrated a residual enhancing lesion measuring 12 × 24 mm along the left middle cerebral artery [Figure 4a]. Serum pro-gastrin-releasing peptide was markedly elevated at 1,250 pg/mL, whereas neuron-specific enolase was 10.1 ng/mL. These findings supported, but did not independently establish, a pulmonary primary.

Figure 4:

Postoperative intracranial imaging course. (a) Early postoperative contrast-enhanced T1-weighted magnetic resonance image (MRI) obtained after maximal safe subtotal resection shows a residual enhancing lesion measuring 12 × 24 mm along the left middle cerebral artery (white arrow). (b) Follow-up contrast-enhanced T1-weighted MRI obtained 7 months after surgery, following whole-brain radiotherapy and systemic chemotherapy, shows interval shrinkage of the residual enhancing lesion without evidence of local progression (white arrow). Because the residual enhancing lesion was small and irregular, with margins indistinct from adjacent postoperative and treatment-related changes, reliable independent size measurement was not possible. (c) Contrast-enhanced T1-weighted MRI obtained 13 months after surgery shows new leptomeningeal enhancement around the brainstem, consistent with leptomeningeal dissemination (white arrow). (d) Contrast-enhanced T1-weighted MRI obtained at the same time shows ventricular enlargement consistent with hydrocephalus (white arrowheads). These findings show initial intracranial control of the residual lesion after adjuvant therapy, followed by leptomeningeal dissemination and hydrocephalus during subsequent disease progression.

Bronchoscopic biopsy was not performed because histopathological examination of the resected intracranial tumor had already demonstrated metastatic small cell carcinoma. On the basis of the intracranial pathological findings and postoperative thoracic and abdominal CT findings, the patient was clinically diagnosed with cTxN2M1c, stage IVB small cell carcinoma of presumed right upper-lobe pulmonary origin, with intracranial and pancreatic metastases. The pulmonary primary lesion was not pathologically confirmed.

Whole-brain radiotherapy at a dose of 30 Gy in 10 fractions was selected due to the preoperative 4.6 cm lesion, residual enhancement along the left middle cerebral artery, and concern for microscopic intracranial disease associated with small cell carcinoma. This was followed by four cycles of carboplatin and etoposide. Immune checkpoint inhibitor therapy was not administered; the contemporaneous medical records did not document a specific reason for its omission.

At 7 months after surgery, contrast-enhanced MRI demonstrated interval reduction of the residual intracranial enhancement without local progression [Figure 4b]. Reliable measurement was not possible because the residual enhancement was small, irregular, and indistinct from adjacent postoperative and treatment-related changes. Surveillance CT obtained approximately 3.5 months after completion of first-line chemotherapy showed enlargement of the presumed pulmonary primary lesion, mediastinal nodal metastases, and the pancreatic-tail metastasis. The treating team considered this a platinum-sensitive relapse, and four additional cycles of carboplatin and etoposide were administered. Subsequent CT showed no further enlargement.

Thirteen months after surgery, the patient developed a decreased level of consciousness. Contrast-enhanced MRI demonstrated leptomeningeal dissemination around the brainstem and hydrocephalus [Figure 4c and d]. A lumboperitoneal shunt did not improve his neurological status. He received palliative care and died 15 months after surgery.

DISCUSSION

Preoperative diagnostic pitfall

The central lesson of this case is the failure to integrate three converging preoperative red flags: An older former smoker with pulmonary emphysema, an abnormal chest radiograph, and a rapidly enlarging dural-based mass with heterogeneous enhancement and extensive edema. In this context, the chest radiographic abnormality should have prompted chest CT before craniotomy. The absence of respiratory symptoms did not exclude the possibility of pulmonary malignancy. Moreover, including metastasis in the differential diagnosis was insufficient because it did not lead to additional systemic workup or alter operative planning. We, therefore, regard the initial diagnostic pathway as a preoperative diagnostic and management pitfall rather than an unavoidable discovery of a previously unsuspected malignancy.

This distinction is clinically important. Preoperative identification of a suspicious thoracic malignancy would not necessarily have precluded intracranial surgery, because the lesion measured 4.6 cm, caused progressive cognitive decline, and was associated with extensive peritumoral edema. However, it could have enabled multidisciplinary assessment of systemic disease burden, neurological urgency, expected prognosis, and the appropriate method of tissue diagnosis before craniotomy. In this patient, symptomatic mass effect would likely still have justified open surgery, but the operative objective should have been framed as tissue diagnosis and symptom-relieving decompression rather than definitive meningioma resection. Recognition of probable metastatic disease could also have supported a conservative operative endpoint once sufficient tissue and adequate decompression had been obtained, avoiding further arachnoid, cisternal, or neurovascular dissection whenever technically feasible. Once the additional frozen-section specimen raised suspicion for metastatic carcinoma and the dissection plane became unsafe near the middle cerebral artery perforators, further aggressive dissection was not justified.

Imaging and pathological diagnosis

Conventional imaging cannot reliably distinguish TTM from an ordinary meningioma; however, rapid growth, heterogeneous or compartmentalized enhancement, disproportionate edema, hemorrhage, necrosis, and atypical perfusion or spectroscopic findings should raise suspicion for a metastatic component.[1,4,5,9,13] In the present case, the combination of rapid enlargement, a focal intratumoral enhancement pattern distinct from that of the surrounding tumor, and extensive edema was not specific for TTM but was sufficiently atypical to justify systemic evaluation for a malignant dural lesion before definitive resection.

TTM should be distinguished from a collision tumor. TTM requires true metastatic growth within a histologically distinct neoplastic recipient tumor, whereas a collision tumor consists of adjacent independent neoplasms without evidence that one has metastasized to the other.[2,17] In this case, the small cell carcinoma component was embedded within a meningothelial meningioma, satisfying the pathological definition of TTM.

Published cases and biological context

PubMed/MEDLINE was searched from database inception through July 1, 2026, using terms related to meningioma (“meningioma,” “intrameningioma,” and “intra-meningioma”), TTM (“tumor-to-tumor metastasis,” “intrameningioma metastasis,” and “metastasis to meningioma”), and pulmonary small cell carcinoma (“small cell lung carcinoma,” “small-cell lung cancer,” “oat cell carcinoma,” “bronchogenic carcinoma,” and “undifferentiated carcinoma”). The reference lists of relevant articles were also screened. We included reports in which metastasis of small cell carcinoma of pulmonary origin to a meningioma was established histopathologically or, when intracranial tissue was unavailable, supported by compelling clinical and radiological evidence. Non-small cell histologies, direct invasion, collision tumors, and insufficiently characterized reports were excluded from the study.

Four previously published cases were identified[1,3,5,7] and are summarized together with the present case in Table 1. Chambers et al. reported a historical autopsy case without modern immunohistochemical confirmation.[3] Allam et al. and Danisman et al. reported histopathologically confirmed surgical cases,[1,5] whereas Georgiou et al. described a clinically and radiologically diagnosed case without intracranial tissue confirmation.[7] Including the present case, the patients were 67–80 years old, four of the five were male, and the median age was 72 years. These numbers are too small to support demographic inferences but reinforce the need to consider systemic malignancy in older patients with risk factors for lung cancer and atypical meningioma-like lesions.

Table 1:

Published cases of small cell lung carcinoma metastatic to meningioma and the present case of small cell carcinoma of presumed pulmonary origin.

Meningiomas may provide a favorable recipient environment due to their rich vascularity, slow growth, low metabolic demand, and collagen- and lipid-rich stroma. Cell adhesion molecules and related pathways may further facilitate metastatic implantation.[8,9,15] Nevertheless, neither meningioma grade nor histological subtype reliably predicts TTM.[18,19]

Oncological course and leptomeningeal dissemination

Recognition of TTM redirected management toward systemic staging and treatment. The residual intracranial lesion initially regressed after whole-brain radiotherapy and chemotherapy, but systemic disease progressed, and leptomeningeal dissemination developed 13 months after surgery. This clinical course likely reflected the aggressive biology of small cell carcinoma. A contribution from surgery cannot be excluded: the Sylvian fissure and cistern were opened, and the lesion was internally decompressed piecemeal. A retrospective study of conventional brain metastases reported an association between piecemeal resection and a higher risk of leptomeningeal dissemination than en bloc resection or stereotactic radiosurgery.[16] However, those data do not specifically address TTM within a meningioma; en bloc resection was not technically safe in this case, and there was no direct evidence of intraoperative tumor-cell spillage. Therefore, a causal relationship cannot be established.

Limitations

This report has several limitations. First, the presumed pulmonary primary lesion was not pathologically confirmed because bronchoscopic biopsy was not performed. Second, no preoperative chest CT was available; therefore, the preoperative radiographic opacity could not be directly correlated with the postoperative central right upper-lobe lesion. Third, our critique of the preoperative decision-making process is retrospective and cannot fully reconstruct all contemporaneous clinical considerations. Fourth, only a few comparable cases have been reported, limiting conclusions regarding characteristic imaging findings or clinical outcomes. Despite these limitations, the intracranial pathological findings and postoperative systemic imaging findings strongly support TTM involving small cell carcinoma of presumed pulmonary origin, and the preoperative diagnostic pathway provides a clinically relevant neurosurgical lesson.

CONCLUSION

The essential lesson of this case lies not in its rarity alone. In an older smoker with an abnormal chest radiograph and a rapidly enlarging, heterogeneously enhancing dural-based mass with marked peritumoral edema, chest CT, and systemic evaluation for malignancy should be completed before definitive resection under a presumptive diagnosis of meningioma whenever clinically feasible. When surgery remains necessary due to mass effect or neurological deterioration, recognition of probable metastatic disease should shift the operative goal toward tissue diagnosis and symptom-relieving decompression rather than presumed definitive meningioma resection. Histopathological examination remains essential for identifying TTM and guiding oncological management.

Ethical approval:

The Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship:

This work was supported by JSPS KAKENHI Grant Numbers JP26K19826 (to S.Y.) and JP25K12362 (to A.U.).

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that artificial intelligence-assisted technology was used to assist with language editing and manuscript organization. All content was critically reviewed and revised by the authors, who take full responsibility for the final manuscript. No images were generated or manipulated using artificial intelligence.

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