1. Case Study 54
Edward D. Plowey

2. Case History
The patient is a 56 year old woman with recent onset seizure-like spells.
The patient has no significant past-medical history.
The patient underwent an MRI study of the brain.

3. Question 1
Describe the findings in the following MRI images:

4. T2 FLAIR T1
T1 + C
T1 + C

5. Answer
Two left middle cranial fossa lesions show small amounts of vasogenic edema. T2 isointense to hypointense (larger, medial lesion). The larger medial lesion shows T1 hyperintensity. Both of these lesions demonstrate avid, homogenous contrast enhancement and dural tails, consistent with meningiomas.

6. Question 2
Formulate a differential diagnosis for these lesions.

7. Answer
The differential diagnosis of this lesion includes: Meningiomas Hemangiopericytomas / Solitary fibrous tumor nodules Melanocytomas Metastatic tumors

8. Question 3: Intraoperative Consultation
The patient was taken to the operating room for left frontal craniotomy and resection of the tumors.
The surgeons noted good resection planes and dark pigmentation in the extra- axial tumors. A gross photograph of the medial tumor is shown:
An intraoperative consultation was performed on the lateral tumor. Identify the pertinent findings in the virtual slide of the intraoperative smear preparation.

9. Diff-Quick Stained Touch Prep (Lateral Tumor)

10. Answer
The intraoperative smear shows a cellular neoplasm with delicate vasculature and extravasated erythrocytes. The epithelioid cells show prominent tapered cytoplasmic stretching which contrasts with the usual pulled-taffy effect in meningothelial cells. High power views show frequent binucleate cells and occasional coarse pigment-containing cells with eccentric nuclei (pigmented macrophages). A few cells have prominent nucleoli, but mitotic figures are difficult to find. Nucleoli and cytoplasmic granules are better appreciated on the Diff-Quick stained touch prep.
Question 4: What is your Intraoperative Diagnosis?

11. Answer Intraoperative diagnosis: A. Neoplastic.
B. Melanocytic neoplasm, defer to permanents for further classification.

12. Question 5: Permanent Sections
Describe the relevant findings on the following virtual permanent section slides of the two excised tumors: Lateral tumor Medial Tumor

13. Answer
A section of the lateral tumor shows sheets of epithelioid cells with granular cytoplasm and round nuclei with nucleoli. Mitotic figures are difficult to identify and there is no significant cellular anaplasia or necrosis. No brain invasion is seen. A few macrophages with coarse pigment are seen in areas with small fresh hemorrhages. The lateral tumor itself shows no significant pigment.
In contrast, the medial tumor shows fascicles of spindled cells and peripheral areas with prominent melanin pigment. The medial tumor also shows a paucity of mitotic figures, no significant anaplasia or necrosis and no brain invasion.

14. Question 5
What immunostains will you order to confirm your diagnostic impressions?

15. Answer Melanocyte differentiation markers, including EMA CD34
Useful immunostains include the following:
Melanocyte differentiation markers, including
Melan A (click to view virtual slides Tumor #1, #2)
EMA
CD34
Pankeratin
Ki67 (click to view virtual slides Tumor #1, #2)

16. Question 6
What information do the special stains convey? What is the final diagnosis?

17. Answer
Melanocyte differentiation markers Melan A, HMB45 and S100 are diffusely and strongly positive.
Immunostains for EMA, CD34 and pankeratin are negative, confirming that the tumors are not meningiomas, HPC/SFT or metastatic carcinomas.
Ki67 immunostains demonstrate very low proliferative indices in both tumors.
Final Diagnosis: MELANOCYTOMAS, WHO GRADE 1.

18. Discussion
Melanocytomas are benign tumors of meningeal melanocytes that are treated with surgical excision. Elevated prevalence of mitotic figures and brain invasion suggest the possibility of more aggressive clinical behavior (recurrence). Progression of melanocytoma to malignant melanoma is the subject of a rare case report (Roser et al., 2004). Primary CNS malignant melanoma is diagnosed with the presence of anaplasia, brisk mitotic activity, necrosis and brain invasion (Brat and Perry, 2007). This diagnosis is made when metastasis from a primary systemic melanoma is ruled out. Melanocytomas most commonly involve regions with the highest densities of leptomeningeal melanocytes, including the posterior fossa, cervical spinal cord and bases of the temporal lobes. Melanocytomas/melanocytosis of the middle cranial fossa may be associated with an ipsilateral nevus of Ota.

19. References
Brat DJ and Perry A. (2007). Melanocytic lesions. In WHO classification of tumours of the central nervous system. Eds. Louis DN, Ohgaki H, Wiestler OD and Cavenee WK. Lyon, France: International Agency for Research on Cancer.
Roser F, Nakamura M, Brandis A, Hans V, Vorkapic P, Samii M. (2004). Transition from meningeal melanocytoma to primary cerebral melanoma. Case report. J Neurosurg. 101: