A Hidden Metastasis with a Bloomy Rind Sign: Carcinomatous Meningitis from Metastatic Lung Adenocarcinoma with Unusual Cranial Nerve Involvement

Abstract

Carcinomatous meningitis, also known as leptomeningeal metastasis, is a rare and often under-recognized manifestation of advanced cancer. It occurs when malignant cells invade the leptomeningeal layers surrounding the brain and spinal cord, leading to a range of neurological symptoms. It remains a diagnostic challenge due to its nonspecific clinical presentation and the complexity of distinguishing it from other neurological conditions. Our case report highlights a rare and unique presentation of carcinomatous meningitis in a patient with an underlying, previously undiagnosed malignancy. The patient initially presented with left-sided facial pain, decreased sensation over the left side of the face, drooling of saliva, and coughing while eating, which raised suspicion for possible posterior fossa lesion. Magnetic resonance imaging (MRI) of the brain with contrast revealed fusiform thickening of the left trigeminal nerve, which was suggestive of a granulomatous lesion. FLAIR also showed bloomy Rind sign. CSF studies showed atypical malignant cells. A multidisciplinary team was set up and endoscopic transnasal transsphenoidal biopsy was done, which was reported as metastatic adenocarcinoma from a primary lung lesion which was confirmed later by PET CT scan. This case emphasizes the importance of considering leptomeningeal metastasis in patients with unexplained neurological signs and symptoms. Multidisciplinary collaboration, including neurosurgery, oncology, and radiology, is essential for accurate diagnosis, staging, and treatment planning. While the prognosis remains poor, early intervention can potentially improve quality of life and extend survival in selected cases.

 

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Keywords

bloomy Rind sign - carcinomatous meningitis - lung adenocarcinoma - malignancy

Introduction

Carcinomatous meningitis (CM) aka leptomeningeal metastasis (LM) is an uncommon and typically late complication of cancer with poor prognosis and limited treatment options. Several clinical series have estimated LM to occur in 4 to 15% of patients with solid tumors, 7 to 15% of patients with lymphomas, 5 to 15% of patients with leukemias, and 1 to 2% of patients with primary brain tumour.[1] The clinical presentation of CM is highly variable, often mimicking other neurological conditions, making it challenging to diagnose early. Better systemic control of a cancer may delay the occurrence of LM; however, once LM is established, the prognosis of the patients is poor and the median survival is around 8 weeks (range: 4–11 weeks).[2] This case highlights the complexity of diagnosing and managing CM, emphasizing the need for a multidisciplinary approach for optimal patient care.

 

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Case Report

A 47-year-old female, with no known comorbidities and no previous hospital admissions, presented with complaints of left facial pain for the past 3 months over V2 and V3 dermatomes. The pain was sharp and shooting in nature, accompanied by diminished sensation over the left half of the face, including touch, temperature, and pain sensations. Additionally, the patient reported difficulty chewing food and coughing while eating. On neurological examination, the patient exhibited diminished sensation over the left V2 and V3 dermatomes to pain, touch, and temperature. The uvula was deviated to the right, and there was atrophy with deviation of the tongue to the left, suggesting involvement of the lower cranial nerves. There was no papilledema, and extraocular movements were full in all directions. Facial symmetry was preserved, with no signs of cortical (lobar) involvement. Higher mental functions were grossly intact, cerebellar signs were absent, and spino-motor examination was within normal limits. Clinical examination revealed features suggestive of probable posterior fossa lesion with cranial nerve involvement. An MRI of the brain was performed, which showed fusiform and striated enhancement of the cisternal and cavernous segments of the left trigeminal nerve, with extension into Meckel's cave ([Fig. 1A]) and the mandibular (V3) division via the foramen ovale ([Fig. 1E]). The lesion further extends along the foramen rotundum into the maxillary division ([Fig. 1D]), with involvement noted in the sphenopalatine foramen, pterygomaxillary fissure, and infratemporal fossa. MRI also revealed STIR hyperintensity and post-contrast enhancement of the left masseter, medial, and lateral pterygoid muscles. FLAIR hyperintensity was noted on an anterior brainstem surface ([Fig. 1F, G]). Bilateral thickening and enhancement of the facial and vestibulocochlear nerves were noted ([Fig. 1B]), although the patient did not report any symptoms related to these nerves. The MRI was suggestive of a granulomatous lesion, with a differential diagnosis including neurosarcoidosis or IgG4-related disease.

Fig. 1 (A) MRI of the brain contrast showed fusiform and striated enhancement of the cisternal and cavernous segments of the left trigeminal nerve, with extension into Meckel's cave. (B) Showing bilateral facial and vestibulocochlear nerve involvement. (C) Ophthalmic division (V1) involvement. (D) Maxillary nerve (V2) involvement and extension through the foramen rotundum. (E) Mandibular nerve (V3) involvement and extension through the foramen ovale. (F) Band-like FLAIR hyperintensity without abnormal enhancement noted along the anterior brainstem surface—blooming Rind sign. It is rare and a characteristic sign for lung adenocarcinoma, and can help in diagnosing. (G) Band-like FLAIR hyperintensity noted along the lower midbrain and upper pons. (H) PET CT showing avidly irregular lobulated lesion in the anterior segment of the left upper lobe. (I) Chest X-ray anteroposterior view – Normal X-ray.

A lumbar puncture was subsequently performed, revealing cerebrospinal fluid (CSF) findings of elevated protein (108.8 mg/dL), normal CSF glucose (40 mg/dL), and a raised white blood cell count (48 cells/μL), predominantly neutrophils. Cultures and stains for viruses, bacteria, and fungi were negative, but cytology was positive for malignant cells ([Fig. 2A–C]).

Fig. 2 (A) CSF cytology—atypical malignant cells with pleomorphism. (B) CSF cytology—atypical cells showing vacuolation. (C) CSF cytology—atypical cell with variable nucleoli size. (D) Histopathology image showing marked atypia with tumor cells (HE × 400). (E) Histopathology image showing necrosis admixed with the tumor cells (HE × 400). (F) Immunohistochemistry—positive immunostaining with TTF1 (× 400). (G) Immunohistochemistry—positive immunostaining with Napsin A (× 400).

In the absence of other systemic symptoms, MRI reports, and cytological examination and in order to confirm the histopathological diagnosis and guide further management, a surgical biopsy was planned. Patient underwent endoscopic transnasal transsphenoidal biopsy of lesion. Histopathological examination confirmed the presence of a metastatic lesion from an unknown primary ([Fig. 2D, E]). Immunohistochemistry revealed positive markers for CK, CK7, CK19, TTF1, and Napsin A ([Fig. 2F, G]), while negative results were obtained for calretinin, CK20, and GATA3, which confirmed the lung as the primary source of the malignancy. A subsequent PET CT scan showed an FDG-avid lobulated lesion in the left upper lobe of the lung (SUVmax ∼9.4), likely primary lung carcinoma ([Fig. 1H]), and FDG-avid dural thickening along the left cavernous sinus, extending to the prepontine cistern. Leptomeningeal enhancement is seen in the bilateral parietal cortex and quadrigeminal cistern. FDG-avid sclerotic lesions are seen in D3, D5, S1, S2 vertebrae, and bilateral ribs and mildly FDG-avid mediastinal and hilar nodes.

A multidisciplinary team was involved and she was started on palliative systemic chemotherapy (Inj Pemetrexed and Inj Carboplatin) every 21 days and weekly intrathecal chemotherapy (Inj Methrotrexate + Inj Cytarabine + Inj Hydrocort) until CSF cytology was negative, and daily whole brain radiation (30 GY in 10 fractions). She showed clinical and symptomatic improvement, with reduced facial pain and improved swallowing noted after the first cycle of chemotherapy. Next-generation sequencing was done, which revealed an epidermal growth factor receptor (EGFR) mutation. She was discharged in stable condition.

 

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Discussion and Comprehensive Review of Literature

CM, or LM, is a rare and often insidious complication of advanced cancer. Most common malignancies associated with LM are breast carcinoma (12–35%), lung carcinoma (10–26%), malignant melanoma (5–25%), gastrointestinal tumors (4–14%), and cancers of unknown primary (1–7%).[3] Diagnoses other than meningeal cancer were considered in most patients at the time of admission due to a varied range of clinical signs and symptoms.

Various mechanisms for the spread of tumor cells to the leptomeninges have been described by different authors. These include hematogenous metastasis to the choroid plexus, which is rare, and primary hematogenous spread through leptomeningeal vessels. Tumor dissemination can also occur via Batson's venous plexus. Among the most commonly described mechanisms is the retrograde spread of tumor cells along perineural lymphatics and nerve sheaths. Another proposed route involves centripetal extension along perivascular lymphatics, allowing tumor cells to reach the leptomeninges from distant sites without gross parenchymal metastasis.[1] [3] In our case, imaging revealed characteristic perineural spread of the lesion, with extension along the trigeminal nerve and further involvement around neural foramina, such as the foramen ovale and foramen rotundum ([Fig. 1D, E]), consistent with dissemination via perineural lymphatic channels.

Molecular and immunological investigations by Boire et al reveal the upregulation of complement component 3 (C3) in LM, suggesting that C3 plays a critical role in facilitating the spread of cancer to the meninges.[4] C3 contributes to the promotion of cancer cell growth in the leptomeningeal space. By interacting with tumor cells, C3 alters the CSF environment, enabling cancer cells to thrive and invade the leptomeninges. It impairs the function of tight junctions within the choroid plexus, which is crucial for maintaining the blood–CSF barrier. This disruption facilitates the movement of tumor cells into the CSF, which affects the composition of CSF and thus creates an environment conducive to tumor growth. The altered CSF composition, resulting from C3 activation, helps tumor cells to adapt, proliferate, and invade the leptomeningeal space.[4]

The patient presents with a range of neurological signs and symptoms in CM typically localize to one or more of three anatomical compartments: the cerebral hemispheres, the posterior fossa and cranial nerves, and the spinal cord or nerve roots. Any or all of these regions may be affected, contributing to the diverse and often multifocal clinical presentation.

Retrospective evaluation revealed two notable findings suggestive of CM: involvement of multiple anatomical sites along the neuroaxis, and a clear mismatch between the extensive neurological signs and the relatively mild subjective symptoms. This dissociation is often seen in meningeal malignancy, where widespread involvement may precede significant clinical complaints.[5]

Neuroimaging plays an important role in supporting a clinical suspicion of LM and in ruling out alternative causes of neurological symptoms. Likewise, CSF analysis is essential to exclude infections or other nonmalignant processes. However, it is crucial to emphasize that the diagnosis of LM cannot rely solely on abnormal imaging findings—it must always be interpreted in conjunction with the patient's overall clinical presentation.[6]

CSF studies often reveal mild pleocytosis with elevated protein and hypoglycorrhachia. In cases of profound hypoglycorrhachia, infectious etiologies should be considered, particularly bacterial and fungal meningitis.[7] While CSF cytology is considered the gold standard for diagnosing LM, it has limited sensitivity—positive in only 54% of cases on first sampling and may remain negative in up to 14% even after three attempts.[8] [9] Serial CSF sampling is recommended when clinical suspicion is high, as initial cytology can be falsely negative. MRI of the brain and contrast shows leptomeningeal enhancement and hydrocephalus, which are the typical features of LM. A few case studies have reported that FLAIR hyperintensity along the brainstem surface, in the absence of abnormal enhancement, is a rare but characteristic finding in meningeal carcinomatosis.[10] We called this characteristic layer of hyperintensity a “bloomy Rind sign”, likely due to the relatively short symptom duration of 3 months. It results possibly from tumor infiltration, cytotoxic oedema, and microinfarction. This sign has been previously reported in lung adenocarcinoma with EGFR mutations.[11] In our case also, the patient had lung adenocarcinoma with a positive EGFR mutation and demonstrated FLAIR hyperintensity along the anterior brainstem surface. While this imaging finding may aid in the diagnosis of CM from lung adenocarcinoma, it is not confirmatory.

The purpose of treatment of LM is twofold[1]: to prolong survival and[2] to ameliorate or stabilize neurologic signs and symptoms which are producing or may lead to serious neurologic disability.[9] Current therapies involve intrathecal pharmacotherapy, systemic pharmacotherapy, and radiotherapy. Intrathecal therapy is widely used; however, studies have shown that there is limited penetration into solid tumor lesions.[12] The strategic management of such cases is highly individualized and largely dependent on the location of the primary lesion, histopathological subtype, immunohistochemistry profile, and molecular characteristics, including specific mutations. Therefore, a case-based approach is most appropriate when dealing with rare presentations such as this.

 

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Conclusion

Carcinomatous meningitis is a rare but devastating complication of systemic malignancies, often presenting with nonspecific and multifocal neurological symptoms that challenge timely diagnosis. This case underscores the critical importance of integrating clinical, radiological, and cytological data for accurate identification and management. The presence of FLAIR hyperintensity over the anterior brainstem surface—described here as the “bloomy Rind sign”—may serve as a subtle yet valuable imaging clue, especially in patients with lung adenocarcinoma and EGFR mutations. While not definitive, such findings should prompt further investigation and raise early suspicion for leptomeningeal spread. A multidisciplinary approach remains essential to optimize care, improve quality of life, and tailor treatment in these complex presentations.

 

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Conflict of Interest

None declared.

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Publication History

Article published online:
22 July 2025