18 December 2024 - Case of the Month #545
All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Month page. To subscribe or unsubscribe to Case of the Month or our other email lists, click here.
Thanks to Dr. Valeria Barresi, University of Verona, Verona, Italy for contributing this case and discussion and to Dr. Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA for reviewing the discussion.
Case of the Month #545
Clinical history:
A 32 year old woman with a clinical history of complex partial type seizures underwent brain MRI, which showed a 2 cm solid cystic lesion without contrast enhancement in the left temporal lobe. Although the lesion remained stable over a one year follow up, the patient underwent surgery due to an increased frequency of seizures. The lesion was completely removed and the patient is in good health with no evidence of recurrence one year after surgery.
Microscopic images:
What is your diagnosis?
Diagnosis: Multinodular and vacuolating neuronal tumor, CNS WHO grade 1
Test questions (answer at the end):
Which of the following features supports the diagnosis of multinodular and vacuolating neuronal tumor (MVNT)?
Discussion:
Multinodular and vacuolating neuronal tumor (MVNT) is a novel tumor type first included in the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) among neuronal tumors (Pathologica 2022;114:447). It mostly affects adults, with a median reported age of 42 years at the time of diagnosis (range 5 - 71 years), with few reports in children. The predominant location is within the deep cortical ribbon or superficial white matter of the temporal lobes (75 - 80%), followed by the frontal lobes and then the parietal and occipital lobes (Brain Pathol 2013;23:515). Patients affected by MVNT typically present with seizures of the complex partial type but this tumor can also be diagnosed incidentally. Magnetic resonance imaging may show characteristic clustering of T2-FLAIR hyperintense nodules in the deep cortex and superficial white matter in the absence of mass effect, edema and contrast enhancement (Acta Neuropathol 2018;135:485). The main histological features of MVNT are the presence of nodules, which can be better appreciated at low magnification, as well as vacuolization of both the tumor cells and matrix. Nodules typically appear pale in contrast to the surrounding matrix and contain monomorphic neuronal tumor cells that display pericellular / cytoplasmic vacuolization, amphophilic or eosinophilic cytoplasm and round vesicular nuclei with distinct nucleoli. Mitoses, microvascular proliferation and necrosis are absent.
MVNT enters the differential diagnosis with other neuronal or glioneuronal tumors that share a preferential location in the temporal lobe and presents clinically with seizures, mainly gangliocytoma, ganglioglioma and dysembryoplastic neuroepithelial tumor (DNET) . Similar to gangliocytoma and ganglioglioma, MVNT lacks or has a weak expression of NeuN in neuronal cells and may show CD34 staining in ramified neural elements. However, in contrast to these tumors, MVNT does not feature dysmorphic or multinucleated neuronal cells and lacks Rosenthal fibers and eosinophilic granular bodies. In addition, neuronal cells in the MVNT display an incompletely mature neuronal phenotype with synaptophysin, nonphopshorylated 200 KDa NFP and MAP2 positivity, co-occurring with Olig2 immunostaining. Although DNET is also characterized by a nodular pattern, its pathognomonic histological feature consisting of NeuN positive cells floating in a mucoid matrix is not observed in MVNT. Finally, although MAPK pathway activating abnormalities have been identified in MVNT, ganglioglioma and DNET, these mostly consist of small indels and hotspot mutations in MAP2K1 or mutations in BRAF other than p. V600E in MVNT, BRAF p. V600E mutations or BRAF fusions in ganglioglioma and FGFR1 alterations in DNET.
MVNT is classified as CNS WHO grade 1, owing to its indolent behavior. Disease progression or recurrence has not been reported after total resection in any case and the tumor residues remain stable after partial or subtotal resection.
Test question answer:
C. Low power nodules and vacuolization of both the tumor cells and matrix. The main histological features of MVNT are the presence of nodules, which can be better appreciated at low magnification, as well as vacuolization of both the tumor cells and matrix. Answer A is incorrect because although MVNT features MAPK signaling abnormalities, including BRAF mutations, the BRAF p. V600E mutation has not been reported in any cases thus far. Answer B is incorrect because MVNT is characterized by the presence of monomorphic neuronal cells, whereas dysmorphic or multinucleated cells are seen in gangliocytoma or in the ganglionic component of ganglioglioma. Answer D is incorrect because MVNT is a benign, indolent tumor with no recurrence risk after surgery; in accordance, mitoses have not been identified in any of the reported cases.
All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Month page. To subscribe or unsubscribe to Case of the Month or our other email lists, click here.
Thanks to Dr. Valeria Barresi, University of Verona, Verona, Italy for contributing this case and discussion and to Dr. Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA for reviewing the discussion.
Website news:
(1) New Board of Reviewers appointments: Dr. Megan Parilla was recently appointed to our Board of Reviewers for Molecular Pathology. Dr. Reggie Thomasson was appointed to our Board of Reviewers for Transfusion Medicine.
(2) Our cancer precursor project is intended to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (now 1,218) and their precursors (now 175). Read the latest essays by Dr. Pernick, including Cancer Precursor Project – Breast Cancers with Precursor Lesions, Part 6a.
(3) Worldwide Directory of Pathologists: Make sure your profile is current by visiting pathologyoutlines.com/directory. Contact Dr. Pernick with questions or suggestions at Nat@PathologyOutlines.com.
Visit and follow our Blog to see recent updates to the website.
(1) New Board of Reviewers appointments: Dr. Megan Parilla was recently appointed to our Board of Reviewers for Molecular Pathology. Dr. Reggie Thomasson was appointed to our Board of Reviewers for Transfusion Medicine.
(2) Our cancer precursor project is intended to better understand how cancer arises by compiling a regularly updated spreadsheet of all distinct human cancers (now 1,218) and their precursors (now 175). Read the latest essays by Dr. Pernick, including Cancer Precursor Project – Breast Cancers with Precursor Lesions, Part 6a.
(3) Worldwide Directory of Pathologists: Make sure your profile is current by visiting pathologyoutlines.com/directory. Contact Dr. Pernick with questions or suggestions at Nat@PathologyOutlines.com.
Visit and follow our Blog to see recent updates to the website.
Case of the Month #545
Clinical history:
A 32 year old woman with a clinical history of complex partial type seizures underwent brain MRI, which showed a 2 cm solid cystic lesion without contrast enhancement in the left temporal lobe. Although the lesion remained stable over a one year follow up, the patient underwent surgery due to an increased frequency of seizures. The lesion was completely removed and the patient is in good health with no evidence of recurrence one year after surgery.
Microscopic images:
What is your diagnosis?
Click here for diagnosis, test question and discussion:
Diagnosis: Multinodular and vacuolating neuronal tumor, CNS WHO grade 1
Test questions (answer at the end):
Which of the following features supports the diagnosis of multinodular and vacuolating neuronal tumor (MVNT)?
- BRAF p. V600E mutation
- Dysmorphic or multinucleated neuronal cells
- Low power nodules and vacuolization of both the tumor cells and matrix
- Mitoses
Discussion:
Multinodular and vacuolating neuronal tumor (MVNT) is a novel tumor type first included in the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) among neuronal tumors (Pathologica 2022;114:447). It mostly affects adults, with a median reported age of 42 years at the time of diagnosis (range 5 - 71 years), with few reports in children. The predominant location is within the deep cortical ribbon or superficial white matter of the temporal lobes (75 - 80%), followed by the frontal lobes and then the parietal and occipital lobes (Brain Pathol 2013;23:515). Patients affected by MVNT typically present with seizures of the complex partial type but this tumor can also be diagnosed incidentally. Magnetic resonance imaging may show characteristic clustering of T2-FLAIR hyperintense nodules in the deep cortex and superficial white matter in the absence of mass effect, edema and contrast enhancement (Acta Neuropathol 2018;135:485). The main histological features of MVNT are the presence of nodules, which can be better appreciated at low magnification, as well as vacuolization of both the tumor cells and matrix. Nodules typically appear pale in contrast to the surrounding matrix and contain monomorphic neuronal tumor cells that display pericellular / cytoplasmic vacuolization, amphophilic or eosinophilic cytoplasm and round vesicular nuclei with distinct nucleoli. Mitoses, microvascular proliferation and necrosis are absent.
MVNT enters the differential diagnosis with other neuronal or glioneuronal tumors that share a preferential location in the temporal lobe and presents clinically with seizures, mainly gangliocytoma, ganglioglioma and dysembryoplastic neuroepithelial tumor (DNET) . Similar to gangliocytoma and ganglioglioma, MVNT lacks or has a weak expression of NeuN in neuronal cells and may show CD34 staining in ramified neural elements. However, in contrast to these tumors, MVNT does not feature dysmorphic or multinucleated neuronal cells and lacks Rosenthal fibers and eosinophilic granular bodies. In addition, neuronal cells in the MVNT display an incompletely mature neuronal phenotype with synaptophysin, nonphopshorylated 200 KDa NFP and MAP2 positivity, co-occurring with Olig2 immunostaining. Although DNET is also characterized by a nodular pattern, its pathognomonic histological feature consisting of NeuN positive cells floating in a mucoid matrix is not observed in MVNT. Finally, although MAPK pathway activating abnormalities have been identified in MVNT, ganglioglioma and DNET, these mostly consist of small indels and hotspot mutations in MAP2K1 or mutations in BRAF other than p. V600E in MVNT, BRAF p. V600E mutations or BRAF fusions in ganglioglioma and FGFR1 alterations in DNET.
MVNT is classified as CNS WHO grade 1, owing to its indolent behavior. Disease progression or recurrence has not been reported after total resection in any case and the tumor residues remain stable after partial or subtotal resection.
Test question answer:
C. Low power nodules and vacuolization of both the tumor cells and matrix. The main histological features of MVNT are the presence of nodules, which can be better appreciated at low magnification, as well as vacuolization of both the tumor cells and matrix. Answer A is incorrect because although MVNT features MAPK signaling abnormalities, including BRAF mutations, the BRAF p. V600E mutation has not been reported in any cases thus far. Answer B is incorrect because MVNT is characterized by the presence of monomorphic neuronal cells, whereas dysmorphic or multinucleated cells are seen in gangliocytoma or in the ganglionic component of ganglioglioma. Answer D is incorrect because MVNT is a benign, indolent tumor with no recurrence risk after surgery; in accordance, mitoses have not been identified in any of the reported cases.
