British Journal of Neurosurgery, April 2015; 29(2): 298–302 © 2015 The Neurosurgical Foundation ISSN: 0268-8697 print / ISSN 1360-046X online DOI: 10.3109/02688697.2014.967752
Primary sellar melanocytic tumor mimicking hemorrhagic pituitary macroadenoma: Case report and literature review Heng-Jun Zhou, Ren-Ya Zhan, Yue-Hui Ma, Fei Cao & Xiu-Jue Zheng
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P. R. China
hypopituitarism, and may mimic hormonally inactive pituitary macroadenoma both clinically and radiologically.12 They include intrasellar and suprasellar lesions as well as benign and malignant types. Trans-sphenoidal surgery was mentioned 13 times in 9 cases as the first choice, whereas only 2 surgeries achieved complete resection4,10 and 3 surgeries only took biopsies due to extensive bleeding.3,8,11 Most cases with incomplete resection were approved for adjuvant radiotherapy.2,5,9,11 However, the appropriate subsequent therapy for patients with complete resection has not been clearly defined4,10 (Table I). We report a case of a Chinese man with a primary sellar melanocytic tumor who developed progressive bitemporal hemianopsia, visual loss, and pituitary insufficiency. He was treated with transfrontal surgery, and was followed up after 7 years.
Abstract Primary melanocytic tumors of the central nervous system (CNS) are rare lesions, but primary sellar tumors are rarer. Only 10 cases have been reported, and they are often misdiagnosed as pituitary macroadenoma. We report the case of a 54-yearold Chinese man who developed progressive bitemporal hemianopsia and visual loss. Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk that was suspected of being a hemorrhagic pituitary macroadenoma. Because of the atypically giant, hemorrhagic, and upward-growing lesion, an initial trans-sphenoidal approach failed, and subsequent transfrontal craniotomy was adopted to achieve macroscopically complete resection. Histopathologic findings revealed a benign melanocytic tumor. Despite an extensive search, no other primary or secondary site was found. Considering the relatively benign lesion, effective surgery, and potential significant consequences of radiotherapy, the patient received no further treatment and is still alive at the 7-year follow-up. Primary sellar melanocytic tumors are exceptional lesions that are difficult to diagnose before operating and/or obtaining pathological findings. The pathological classification and extent of surgical resection may play a key role in the prognosis. Once this type of lesion is suspected, the transfrontal approach may achieve preferable exposure and resection. Complete surgical resection may be sufficient for relatively benign lesions; otherwise, stereotactic fractionated radiotherapy is indicated. More cases should be reported to improve the treatment strategy.
Case report History and examination In May 2006, a 54-year-old Chinese man presented at our department with progressing visual deterioration for 2 years. He had a 4-year history of diabetes mellitus and it was controlled through diet. Ophthalmological examination revealed bitemporal hemianopsia and reduced visual acuity that was more apparent in his right eye (visual acuity: right eye, 0.2; left eye, 0.6). General examination of the patient was otherwise unremarkable. Endocrinological evaluation revealed borderline hypogonadism (luteinizing hormone [LH] ⫽ 0.8 mIU/mL [normal, 0.8–7.6]; follicle-stimulating hormone [FSH] ⫽ 0.7 mIU/mL [normal, 0.7–11.1]), prominent hypothyroidism (thyroid stimulating hormone [TSH] ⫽ 0.58 mIU/ mL [normal, 0.40–4.00]; free T4 ⫽ 3.86 pmol/L [normal, 10.30–24.45]), and normal adrenocorticotropic hormone level (ACTH [8:00 a.m.] ⫽ 31.1 pg/mL [normal, 0.0–46.0]; ACTH [4:00 p.m.] ⫽ 17.9 pg/mL [normal, 0.0–23.0]). The prolactin level was prominently decreased (prolactin ⫽ 1.1 ng/mL [normal, 2.5–17.0]). Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk. On
Keywords: melanocytic tumor; primary; pituitary macroadenoma; sellar; transfrontal
Primary melanocytic tumors of the central nervous system (CNS) are rare lesions, accounting for less than 0.1% of all brain tumors, which arise from melanocytes of the leptomeninges.1 Primary sellar melanocytic tumors are rarer, and only 10 cases have been reported in the literature.2–11 These lesions can cause progressive tumor syndrome and
Correspondence: Xiu-Jue Zheng, Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, P. R. China. E-mail: [email protected] Received for publication 16 April 2014; accepted 14 September 2014
298
35/F
47/M
37/F
25/F
63/F 61/F
82/F
54/M
Copeland et al.4
Aubin et al.2
Uematsu et al.15
Albrecht et al.12
Scholtz and Siu8 Classen et al.17
Jellinger et al.14
Current case
M, male; F, female; VL, visual loss; VFD, visual field defect; T1WI, T1-weighted images; T2WI, T2-weighted images; HyperI, hyperintense; HypoI, hypointense; Gd, gadolinium; TFSR, transfrontal surgical resection; TSSR, transsphenoidal surgical resection; TSB, trans-sphenoidal biopsy; RT, radiotherapy; CT, chemotherapy.
Alive (7 yr) Follow up (2 yr) No TSB ⫹ TFSR (complete)
— —
Deceased (3 mo) — — —
RT RT (54 Gy) beam RT TSSR (incomplete) TSB ⫹ TSSR (incomplete) TSSR (incomplete)
Alive (24 mo)
37/F Neilson and Moffat6
VFD, VL (2 weeks)
HyperI rim surrounding a slightly HypoI center on T1WI and the opposite on T2WI. Minor Gd enhancement of the rim. Amenorrhea, VFD, VL (4 yr) HyperI on T1WI and T2WI. Intense, homogeneous Gd enhancement. Headache, Diplopia (4 weeks) HypoI on T1WI. Intense Gd enhancement of the rim. VFD, Hypopituitarism HypoI on T1WI and HyperI on T2WI. Intense, homogeneous (2 months) Gd enhancement. Ophthalmoplegia Homogeneous Gd enhancement. (4 months) VFD, VL (2 yr) HyperI wide band surrounding a HypoI center on T1WI and the opposite on T2WI. Intense Gd enhancement of the wide band.
No No TSSR (incomplete)
Alive (24 mo)
TSSR (incomplete) (8 mo) and TSSR (incomplete) (10 mo) RT (40.4 Gy) No TSSR (complete)
RT (60 Gy) TSSR (incomplete)
Deceased (16 mo)
No
—
— —
Hypopituitarism (3 yr) VFD, VL, retro-orbital pain (18 months) VL (several weeks) 62/M 54/M Vezzosi et al.11 Hayward13
Oligomenorrhea, galactorrhea HyperI on T1WI and HypoI on T2WI (3 yr) Hypopituitarism, headache HyperI on T1WI and HypoI on T2WI (6 months)
TSB
TSSR and CT (incomplete) Deceased (41 mo) (18 mo) — Alive (3 mo) No TSSR (complete)
Deceased (3 yr) Deceased (2 wk) — — No No No TSB
Subsequent strategy Operation (extent) MRI Clinical symptoms (duration) Age (years)/ Sex (M/F) References
Table I. Clinical features of primary sellar melanocytic tumors reported in the literature.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Regrowth or recurrence strategy (extent) (time)
Fllow-up status (time after operation)
Primary sellar melanocytic tumor
299
T1-weighted imaging, the lesion appeared as a hyperintense wide band surrounding a hypointense narrow center, mimicking a cloud (Fig. 1A). There was high-contrast enhancement of the wide band after gadolinium administration (Fig. 1B). On T2-weighted imaging, the lesion appeared as a hypointense wide band with a heterogeneous center (Fig. 1C). Based on the clinical and radiological features, the lesion was assumed to be an atypical hemorrhagic pituitary macroadenoma, and trans-sphenoidal surgery was initially performed.
Operation An initial trans-sphenoidal approach failed due to the atypically giant, hemorrhagic, and upward growing lesion, and subsequent transfrontal craniotomy was performed. The lesion appeared fibrous, rigid, and brownish-black with rich intratumoral hemorrhage (Fig. 2A; see Supplemantary Video to be found online at http://informahealthcare.com/doi/abs/ 10.3109/02688697.2014.967752, which shows the approach of transfrontal craniotomy for resecting the primary sellar melanocytic tumor). Careful surgical operation was performed through the first and second gaps, offering adequate tumor exposure and blood control, making macroscopically complete resection possible. The optic chiasm, hypothalamus, and hypophyseal stalk were completely preserved (Fig. 2B).
Pathological findings Neuropathological examination disclosed pleomorphic cells with abundant brown to black cytoplasmic pigment in a granular pattern arranged in a cordonal or trabecular pattern. Hemorrhagic areas were noted. The lesion was immunopositive for S-100 protein, HMB-45 (Fig. 3), and vimentin, and immunonegative for pituitary hormones, cytokeratin, and glial fibrillary acidic protein (GFAP). Approximately 1–2% of the cells expressed the proliferation marker, Ki-67. No other primary or secondary melanocytic site was found during an extensive search that included dermatological and ophthalmological examinations; computed tomography (CT) scanning of the chest, abdomen, and pelvis; and positron emission tomography (PET) scanning. Based on all of these findings, a primary sellar benign melanocytic tumor was finally diagnosed.
Postoperative course In the postoperative period, the patient’s vision and bitemporal hemianopsia improved (visual acuity: right eye, 0.4; left eye, 0.8). Considering the relatively benign lesion, effective surgery, and potential significant consequences of radiotherapy, the patient received no further treatment. Follow-up MRI performed 1-month post surgery revealed no residual tumor, and local meningeal thickening could still be observed (Fig. 2B); however, the tumor recurred in the 2-year review (Fig. 2C) and was found to have grown very slowly by the 7-year follow-up (Fig. 2D,E). Presently, the patient is still alive and is currently experiencing his initial symptoms.
Discussion Primary sellar melanocytic tumors are very rare. Only 10 cases have been reported thus far (Table I). Based on clinical
300
R.-Y. Zhan et al.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Fig. 1. MRI before surgery showing an intrasellar and suprasellar clouded lesion. (A) Coronal T1-weighted image showing a hyperintense wide band surrounding a hypointense narrow center, mimicking a cloud. (B) Coronal T1-weighted image after gadolinium administration showing the high-contrast-enhanced wide band. (C) Coronal T2-weighted image showing a hypointense wide band with a heterogeneous center.
Fig. 2. Intraoperative and postoperative long-term follow-up results of the patient. (A) Intraoperative image showing a fibrous, rigid, and brownishblack lesion with rich intratumoral hemorrhage. (B) Sagittal T2-weighted image performed 1 month post surgery showing no residual tumor, with local meningeal thickening. The optic chiasm, hypothalamus, and hypophyseal stalk are completely preserved. (C) Axial T1-weighted image showing that the lesion recurred at the 2-year follow-up. (D) and (E) Coronal T1-weighted image showing that the lesion grew slowly by the 5-year and 7-year follow-ups.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Primary sellar melanocytic tumor
Fig. 3. Immunohistochemical photograph of the melanocytic tumor showing diffuse staining for HMB-45 with prominent brown melanin pigments 400⫻.
and radiological features, atypical pituitary macroadenoma is initially assumed, and the very rare sellar melanocytic tumor is only considered after obtaining pathological findings. These tumors mainly develop in the posterior fossa, usually ventral to the brainstem or adjacent to the foramen magnum.1 They may also be found on the inferior surfaces of the frontal, temporal, and occipital lobes. Their affinity for these sites may be attributed to the physiological concentration of leptomeningeal melanocytes at these locations. Thus, sellar melanocytic tumors may originate from melanocytes in the meningeal lining of the sellar floor or in the diaphragma sellae.10 No evidence-based guidelines exist for the diagnosis of primary sellar melanocytic tumors. Combined with the Hayward proposition,13 the following factors are meaningful: no malignant melanoma outside of the CNS, involvement of the sellar leptomeninges, and a single sellar lesion. Thus, a primary sellar melanocytic tumor is established only after exclusion of secondary metastatic disease from a cutaneous, mucosal, or retinal primary tumor, in addition to histopathologic confirmation of the sellar lesion.14 Primary sellar melanocytic tumors are always detected because of a progressive tumor syndrome with impairment of the visual field and anterior pituitary dysfunction. Unlike previously reported cases, our patient had a very long duration of symptoms before admission. The prolactin level was prominently decreased, a finding that was contrary to the most normal-level cases7,10 and high-level cases.2,3 After a macroscopically complete resection was performed through transfrontal craniotomy, the patient had a very long follow-up time. The MRI signal of sellar melanotic lesions, either primary or metastatic, is always confused with atypical hemorrhagic pituitary macroadenoma. There is a dipole–dipole interaction between unpaired electrons of the stable organic free radicals of melanin and water protons. This results in shortening of both T1 and T2 relaxation times, thereby producing
301
hyperintensity in T1-weighted images and hypointensity in T2-weighted images.15 The shortening of the relaxation time is proportional to the melanin content of the tumor.16 Intratumoral hemorrhage produces heterogeneous signals on T1 and T2 sequences depending on the duration of the bleeding. Our MRI data are consistent with most reported cases; meanwhile, Rousseau et al.,7 Jacob et al.,5 and Vezzosi et al.11 described different T1 and/or T2-weighted imaging results (Table I). We speculate that the differences may be related to the distribution of melanocytes or intratumoral hemorrhage. Also, sellar melanoma in those studies mostly appeared as an oval or snowman-like shape on MRI. However, our case showed cloud-like proliferation, with wide band enhancement and a heterogeneous center, very rare features that have never been reported before. Although the relevant criteria for discriminating between benign and malignant categories have not been recognized unanimously, Rousseau et al.7 considered some pathological criteria that may be valuable for classifying melanocytic proliferations. The benign categories always contain monomorphic cells with regular, oval, or bean-shaped nuclei and small, regular nucleoli. The mitotic index is usually low without necrosis, hemorrhage, or CNS invasion. In contrast, the malignant categories are prone to contain pleomorphic, atypical cells. They contain hyperchromatic, enlarged nuclei and large, multiple nucleoli. The mitotic index is usually very high with necrosis and hemorrhage. The pathological findings of our patient indicated a slow proliferative ratio with benign biological behavior: pleomorphic cells with abundant brown to black cytoplasmic pigment arranged in a cordonal or trabecular pattern; and very low expression of proliferation marker Ki-67. Nonetheless, the lesion also displayed some malignant MRI and pathological features: a cloud shape, high-contrast enhancement, invasive growth, pleomorphism, and hemorrhagic center. We believe that the architecture and cellular features play a key role. Due to the rarity of primary sellar melanocytic tumors, most cases will be preoperatively misinterpreted as nonsecretory, possibly hemorrhagic, pituitary adenomas and thus will be approached trans-sphenoidally. Scholtz and Siu8 had first described the trans-sphenoidal approach for resecting primary sellar melanocytic tumors, and a series of other reports also attempted to use the same approach.2–5,7,9–11 However, the lesions are atypically firm and bloody, making complete tumor resection impossible in most cases without injury of the diaphragma sellae or cavernous sinus.11 Only two cases4,10 achieved complete surgical resection in nine trans-sphenoidal cases, and three surgeries could only take biopsies.3,8,11 Thus, some authors recommended radiotherapy of the sellar and parasellar region.2,3,7,10 In our patient, the initial trans-sphenoidal approach also failed; thus, we chose transfrontal craniotomy. Although the tumor appeared fibrous, rigid, and brownish-black (Fig. 2A), adequate surgical field exposure, bleeding control, and careful surgical operation made macroscopically complete resection possible (Fig. 2B). Other authors did not recommend routine radiotherapy after total resection.17 As illustrated herein, although the tumor recurred at the 2-year review (Fig. 2C), we suggest
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
302
R.-Y. Zhan et al.
that due to its relatively benign pathological findings it may not require adjuvant radiotherapy, and close follow-up may be an appropriate strategy after complete resection. To date, there are no treatment consensus guidelines for primary sellar melanocytic tumor, but complete surgical resection is the first recommended strategy if possible.7,17 In our opinion, transfrontal craniotomy could make complete tumor resection more feasible and safe, and the relatively benign tumor is not sensitive to radiotherapy. If complete surgical resection is achieved, clinical and MRI follow-up studies are recommended. Otherwise, stereotactic fractionated radiotherapy is indicated in most incomplete resection cases and intermediate or malignant cases. More cases should be reported to improve the treatment strategy. The prognosis of primary sellar melanocytic tumor is variable but seems to be related with benign or malignant categories and whether complete resection is performed. According to a review of the literature, half of the patients with primary sellar melanocytic tumor were alive after 2 years of follow-up (Table I), and the longest survival reported was 3.5 years.4 Our report doubles the longest survival follow-up time and provides a new treatment strategy for this disease.
Conclusions Primary sellar melanocytic tumors are exceptional lesions that are difficult to diagnose. Pathological classification and surgical resection extent may play a key role in the prognosis of these tumors. As surgical resection is often incomplete through the trans-sphenoidal approach, we suggest that the transfrontal approach achieves preferable exposure and resection once this type of lesion is suspected. Complete surgical resection may be sufficient for relatively benign lesions; otherwise, stereotactic fractionated radiotherapy is indicated. More cases should be reported to improve the treatment strategy.
Declaration financial or materials, or is supported
of interest: The authors have no personal institutional interest in any of the drugs, devices described in this article. This article by a national clinical key specialty construc-
tion projects in China and technology program of Zhejiang province (2013C33123).
References 1. Liubinas SV, Maartens N, Drummond KJ. Primary melanocytic neoplasms of the central nervous system. J Clin Neurosci 2010;17:1227–32. 2. Aubin MJ, Hardy J, Comtois R. Primary sellar haemorrhagic melanoma: case report and review of the literature. Br J Neurosurg 1997;11:80–3. 3. Chappell PM, Kelly WM, Ercius M. Primary sellar melanoma simulating hemorrhagic pituitary-adenoma: MR and pathological findings. Am J Neuroradiol 1990;11:1054–6. 4. Copeland DD, Sink JD, Seigler HF. Primary intra-cranical melanoma presenting as a suprasellar tumor. Neurosurgery 1980;6:542–5. 5. Jacob S, Pye E, Hbahbih M, Messios N, Rajabally YA. Rapidly progressive bilateral ophthalmoplegia and enlarging sellar mass caused by amelanotic melanoma. J Neuroophthalmol 2006;26:49–50. 6. Neilson JM, Moffat AD. Hypopituitarism caused by a melanoma of the pituitary gland. J Clin Pathol 1963;16:144–9. 7. Rousseau A , Bernier M, Kujas M, Varlet P. Primary intracranial melanocytic tumor simulating pituitary macroadenoma: case report and review of the literature. Neurosurgery 2005;57: E369. 8. Scholtz CL, Siu K . Melanoma of pituitary. Case report. J Neurosurg 1976;45:101–3. 9. Sidiropoulos M, Syro LV, Rotondo F, et al. Melanoma of the sellar region mimicking pituitary adenoma. Neuropathology 2013;33:175–8. 10. Tüttenberg J, Fink W, Back W, et al. A rare primary sellar melanoma. Case report. J Neurosurgery 2004;100:931–4. 11. Vezzosi D, Capuani C, Loubes-Lacroix F, et al. Primary sellar melanocytic tumor: report of new case and literature review. Pituitary 2009;12:51–6. 12. Albrecht S, Bilbao JM, Kovacs K. Non pituitary tumors of the sellar region. In: Melmed S, ed. The Pituitary, 2nd ed. Massachusetts: Black-well Publishing, 2002:592–609. 13. Hayward RD. Malignant-melanoma and central nervous-system. A guide for classification based on clinical findings. J Neurol Neurosurg Psychiatry 1976;39:526–30. 14. Jellinger K, Chou P, Paulus W. Melanocytic lesions. In: Kleihues P, Cavenee WK , eds. Pathology and Genetics of Tumours of the Nervous System: World Health Organization Classification of Tumors. Lyon: International Agency for Research on Cancer, 2000:193–195. 15. Uematsu Y, Yukawa S, Yokote H, et al. Meningeal melanocytoma: magnetic-resonance-imaging characteristics and pathological features. Case report. J Neurosurg 1992;76:705–9. 16. Barkovich AJ, Frieden IJ, Williams ML. MR of neurocutaneous melanosis. Am J Neuroradiol 1994;15:859–67. 17. Classen J, Hehr T, Paulus W, Bamberg M. Suprasellar melanocytoma: a case of primary radiotherapy and review of the literature. J Neurooncol 2002;58:39–46.
Supplementary material available online Supplemental Video. This video shows the approach of transfrontal craniotomy to resect the primary sellar giant melanocytic tumor. An initial trans-sphenoidal approach failed due to the atypically giant, hemorrhagic, and upward growing lesion, and subsequent transfrontal craniotomy was performed. The
lesion appeared fibrous, rigid, and brownish-black with rich intratumoral hemorrhage. Careful surgical operation was performed through the fi rst and second gaps, offering adequate tumor exposure and blood control, making macroscopically complete resection possible. The optic chiasm, hypothalamus, and hypophyseal stalk were completely reserved.
Primary sellar melanocytic tumor mimicking hemorrhagic pituitary macroadenoma: Case report and literature review Heng-Jun Zhou, Ren-Ya Zhan, Yue-Hui Ma, Fei Cao & Xiu-Jue Zheng
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P. R. China
hypopituitarism, and may mimic hormonally inactive pituitary macroadenoma both clinically and radiologically.12 They include intrasellar and suprasellar lesions as well as benign and malignant types. Trans-sphenoidal surgery was mentioned 13 times in 9 cases as the first choice, whereas only 2 surgeries achieved complete resection4,10 and 3 surgeries only took biopsies due to extensive bleeding.3,8,11 Most cases with incomplete resection were approved for adjuvant radiotherapy.2,5,9,11 However, the appropriate subsequent therapy for patients with complete resection has not been clearly defined4,10 (Table I). We report a case of a Chinese man with a primary sellar melanocytic tumor who developed progressive bitemporal hemianopsia, visual loss, and pituitary insufficiency. He was treated with transfrontal surgery, and was followed up after 7 years.
Abstract Primary melanocytic tumors of the central nervous system (CNS) are rare lesions, but primary sellar tumors are rarer. Only 10 cases have been reported, and they are often misdiagnosed as pituitary macroadenoma. We report the case of a 54-yearold Chinese man who developed progressive bitemporal hemianopsia and visual loss. Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk that was suspected of being a hemorrhagic pituitary macroadenoma. Because of the atypically giant, hemorrhagic, and upward-growing lesion, an initial trans-sphenoidal approach failed, and subsequent transfrontal craniotomy was adopted to achieve macroscopically complete resection. Histopathologic findings revealed a benign melanocytic tumor. Despite an extensive search, no other primary or secondary site was found. Considering the relatively benign lesion, effective surgery, and potential significant consequences of radiotherapy, the patient received no further treatment and is still alive at the 7-year follow-up. Primary sellar melanocytic tumors are exceptional lesions that are difficult to diagnose before operating and/or obtaining pathological findings. The pathological classification and extent of surgical resection may play a key role in the prognosis. Once this type of lesion is suspected, the transfrontal approach may achieve preferable exposure and resection. Complete surgical resection may be sufficient for relatively benign lesions; otherwise, stereotactic fractionated radiotherapy is indicated. More cases should be reported to improve the treatment strategy.
Case report History and examination In May 2006, a 54-year-old Chinese man presented at our department with progressing visual deterioration for 2 years. He had a 4-year history of diabetes mellitus and it was controlled through diet. Ophthalmological examination revealed bitemporal hemianopsia and reduced visual acuity that was more apparent in his right eye (visual acuity: right eye, 0.2; left eye, 0.6). General examination of the patient was otherwise unremarkable. Endocrinological evaluation revealed borderline hypogonadism (luteinizing hormone [LH] ⫽ 0.8 mIU/mL [normal, 0.8–7.6]; follicle-stimulating hormone [FSH] ⫽ 0.7 mIU/mL [normal, 0.7–11.1]), prominent hypothyroidism (thyroid stimulating hormone [TSH] ⫽ 0.58 mIU/ mL [normal, 0.40–4.00]; free T4 ⫽ 3.86 pmol/L [normal, 10.30–24.45]), and normal adrenocorticotropic hormone level (ACTH [8:00 a.m.] ⫽ 31.1 pg/mL [normal, 0.0–46.0]; ACTH [4:00 p.m.] ⫽ 17.9 pg/mL [normal, 0.0–23.0]). The prolactin level was prominently decreased (prolactin ⫽ 1.1 ng/mL [normal, 2.5–17.0]). Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk. On
Keywords: melanocytic tumor; primary; pituitary macroadenoma; sellar; transfrontal
Primary melanocytic tumors of the central nervous system (CNS) are rare lesions, accounting for less than 0.1% of all brain tumors, which arise from melanocytes of the leptomeninges.1 Primary sellar melanocytic tumors are rarer, and only 10 cases have been reported in the literature.2–11 These lesions can cause progressive tumor syndrome and
Correspondence: Xiu-Jue Zheng, Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, P. R. China. E-mail: [email protected] Received for publication 16 April 2014; accepted 14 September 2014
298
35/F
47/M
37/F
25/F
63/F 61/F
82/F
54/M
Copeland et al.4
Aubin et al.2
Uematsu et al.15
Albrecht et al.12
Scholtz and Siu8 Classen et al.17
Jellinger et al.14
Current case
M, male; F, female; VL, visual loss; VFD, visual field defect; T1WI, T1-weighted images; T2WI, T2-weighted images; HyperI, hyperintense; HypoI, hypointense; Gd, gadolinium; TFSR, transfrontal surgical resection; TSSR, transsphenoidal surgical resection; TSB, trans-sphenoidal biopsy; RT, radiotherapy; CT, chemotherapy.
Alive (7 yr) Follow up (2 yr) No TSB ⫹ TFSR (complete)
— —
Deceased (3 mo) — — —
RT RT (54 Gy) beam RT TSSR (incomplete) TSB ⫹ TSSR (incomplete) TSSR (incomplete)
Alive (24 mo)
37/F Neilson and Moffat6
VFD, VL (2 weeks)
HyperI rim surrounding a slightly HypoI center on T1WI and the opposite on T2WI. Minor Gd enhancement of the rim. Amenorrhea, VFD, VL (4 yr) HyperI on T1WI and T2WI. Intense, homogeneous Gd enhancement. Headache, Diplopia (4 weeks) HypoI on T1WI. Intense Gd enhancement of the rim. VFD, Hypopituitarism HypoI on T1WI and HyperI on T2WI. Intense, homogeneous (2 months) Gd enhancement. Ophthalmoplegia Homogeneous Gd enhancement. (4 months) VFD, VL (2 yr) HyperI wide band surrounding a HypoI center on T1WI and the opposite on T2WI. Intense Gd enhancement of the wide band.
No No TSSR (incomplete)
Alive (24 mo)
TSSR (incomplete) (8 mo) and TSSR (incomplete) (10 mo) RT (40.4 Gy) No TSSR (complete)
RT (60 Gy) TSSR (incomplete)
Deceased (16 mo)
No
—
— —
Hypopituitarism (3 yr) VFD, VL, retro-orbital pain (18 months) VL (several weeks) 62/M 54/M Vezzosi et al.11 Hayward13
Oligomenorrhea, galactorrhea HyperI on T1WI and HypoI on T2WI (3 yr) Hypopituitarism, headache HyperI on T1WI and HypoI on T2WI (6 months)
TSB
TSSR and CT (incomplete) Deceased (41 mo) (18 mo) — Alive (3 mo) No TSSR (complete)
Deceased (3 yr) Deceased (2 wk) — — No No No TSB
Subsequent strategy Operation (extent) MRI Clinical symptoms (duration) Age (years)/ Sex (M/F) References
Table I. Clinical features of primary sellar melanocytic tumors reported in the literature.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Regrowth or recurrence strategy (extent) (time)
Fllow-up status (time after operation)
Primary sellar melanocytic tumor
299
T1-weighted imaging, the lesion appeared as a hyperintense wide band surrounding a hypointense narrow center, mimicking a cloud (Fig. 1A). There was high-contrast enhancement of the wide band after gadolinium administration (Fig. 1B). On T2-weighted imaging, the lesion appeared as a hypointense wide band with a heterogeneous center (Fig. 1C). Based on the clinical and radiological features, the lesion was assumed to be an atypical hemorrhagic pituitary macroadenoma, and trans-sphenoidal surgery was initially performed.
Operation An initial trans-sphenoidal approach failed due to the atypically giant, hemorrhagic, and upward growing lesion, and subsequent transfrontal craniotomy was performed. The lesion appeared fibrous, rigid, and brownish-black with rich intratumoral hemorrhage (Fig. 2A; see Supplemantary Video to be found online at http://informahealthcare.com/doi/abs/ 10.3109/02688697.2014.967752, which shows the approach of transfrontal craniotomy for resecting the primary sellar melanocytic tumor). Careful surgical operation was performed through the first and second gaps, offering adequate tumor exposure and blood control, making macroscopically complete resection possible. The optic chiasm, hypothalamus, and hypophyseal stalk were completely preserved (Fig. 2B).
Pathological findings Neuropathological examination disclosed pleomorphic cells with abundant brown to black cytoplasmic pigment in a granular pattern arranged in a cordonal or trabecular pattern. Hemorrhagic areas were noted. The lesion was immunopositive for S-100 protein, HMB-45 (Fig. 3), and vimentin, and immunonegative for pituitary hormones, cytokeratin, and glial fibrillary acidic protein (GFAP). Approximately 1–2% of the cells expressed the proliferation marker, Ki-67. No other primary or secondary melanocytic site was found during an extensive search that included dermatological and ophthalmological examinations; computed tomography (CT) scanning of the chest, abdomen, and pelvis; and positron emission tomography (PET) scanning. Based on all of these findings, a primary sellar benign melanocytic tumor was finally diagnosed.
Postoperative course In the postoperative period, the patient’s vision and bitemporal hemianopsia improved (visual acuity: right eye, 0.4; left eye, 0.8). Considering the relatively benign lesion, effective surgery, and potential significant consequences of radiotherapy, the patient received no further treatment. Follow-up MRI performed 1-month post surgery revealed no residual tumor, and local meningeal thickening could still be observed (Fig. 2B); however, the tumor recurred in the 2-year review (Fig. 2C) and was found to have grown very slowly by the 7-year follow-up (Fig. 2D,E). Presently, the patient is still alive and is currently experiencing his initial symptoms.
Discussion Primary sellar melanocytic tumors are very rare. Only 10 cases have been reported thus far (Table I). Based on clinical
300
R.-Y. Zhan et al.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Fig. 1. MRI before surgery showing an intrasellar and suprasellar clouded lesion. (A) Coronal T1-weighted image showing a hyperintense wide band surrounding a hypointense narrow center, mimicking a cloud. (B) Coronal T1-weighted image after gadolinium administration showing the high-contrast-enhanced wide band. (C) Coronal T2-weighted image showing a hypointense wide band with a heterogeneous center.
Fig. 2. Intraoperative and postoperative long-term follow-up results of the patient. (A) Intraoperative image showing a fibrous, rigid, and brownishblack lesion with rich intratumoral hemorrhage. (B) Sagittal T2-weighted image performed 1 month post surgery showing no residual tumor, with local meningeal thickening. The optic chiasm, hypothalamus, and hypophyseal stalk are completely preserved. (C) Axial T1-weighted image showing that the lesion recurred at the 2-year follow-up. (D) and (E) Coronal T1-weighted image showing that the lesion grew slowly by the 5-year and 7-year follow-ups.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Primary sellar melanocytic tumor
Fig. 3. Immunohistochemical photograph of the melanocytic tumor showing diffuse staining for HMB-45 with prominent brown melanin pigments 400⫻.
and radiological features, atypical pituitary macroadenoma is initially assumed, and the very rare sellar melanocytic tumor is only considered after obtaining pathological findings. These tumors mainly develop in the posterior fossa, usually ventral to the brainstem or adjacent to the foramen magnum.1 They may also be found on the inferior surfaces of the frontal, temporal, and occipital lobes. Their affinity for these sites may be attributed to the physiological concentration of leptomeningeal melanocytes at these locations. Thus, sellar melanocytic tumors may originate from melanocytes in the meningeal lining of the sellar floor or in the diaphragma sellae.10 No evidence-based guidelines exist for the diagnosis of primary sellar melanocytic tumors. Combined with the Hayward proposition,13 the following factors are meaningful: no malignant melanoma outside of the CNS, involvement of the sellar leptomeninges, and a single sellar lesion. Thus, a primary sellar melanocytic tumor is established only after exclusion of secondary metastatic disease from a cutaneous, mucosal, or retinal primary tumor, in addition to histopathologic confirmation of the sellar lesion.14 Primary sellar melanocytic tumors are always detected because of a progressive tumor syndrome with impairment of the visual field and anterior pituitary dysfunction. Unlike previously reported cases, our patient had a very long duration of symptoms before admission. The prolactin level was prominently decreased, a finding that was contrary to the most normal-level cases7,10 and high-level cases.2,3 After a macroscopically complete resection was performed through transfrontal craniotomy, the patient had a very long follow-up time. The MRI signal of sellar melanotic lesions, either primary or metastatic, is always confused with atypical hemorrhagic pituitary macroadenoma. There is a dipole–dipole interaction between unpaired electrons of the stable organic free radicals of melanin and water protons. This results in shortening of both T1 and T2 relaxation times, thereby producing
301
hyperintensity in T1-weighted images and hypointensity in T2-weighted images.15 The shortening of the relaxation time is proportional to the melanin content of the tumor.16 Intratumoral hemorrhage produces heterogeneous signals on T1 and T2 sequences depending on the duration of the bleeding. Our MRI data are consistent with most reported cases; meanwhile, Rousseau et al.,7 Jacob et al.,5 and Vezzosi et al.11 described different T1 and/or T2-weighted imaging results (Table I). We speculate that the differences may be related to the distribution of melanocytes or intratumoral hemorrhage. Also, sellar melanoma in those studies mostly appeared as an oval or snowman-like shape on MRI. However, our case showed cloud-like proliferation, with wide band enhancement and a heterogeneous center, very rare features that have never been reported before. Although the relevant criteria for discriminating between benign and malignant categories have not been recognized unanimously, Rousseau et al.7 considered some pathological criteria that may be valuable for classifying melanocytic proliferations. The benign categories always contain monomorphic cells with regular, oval, or bean-shaped nuclei and small, regular nucleoli. The mitotic index is usually low without necrosis, hemorrhage, or CNS invasion. In contrast, the malignant categories are prone to contain pleomorphic, atypical cells. They contain hyperchromatic, enlarged nuclei and large, multiple nucleoli. The mitotic index is usually very high with necrosis and hemorrhage. The pathological findings of our patient indicated a slow proliferative ratio with benign biological behavior: pleomorphic cells with abundant brown to black cytoplasmic pigment arranged in a cordonal or trabecular pattern; and very low expression of proliferation marker Ki-67. Nonetheless, the lesion also displayed some malignant MRI and pathological features: a cloud shape, high-contrast enhancement, invasive growth, pleomorphism, and hemorrhagic center. We believe that the architecture and cellular features play a key role. Due to the rarity of primary sellar melanocytic tumors, most cases will be preoperatively misinterpreted as nonsecretory, possibly hemorrhagic, pituitary adenomas and thus will be approached trans-sphenoidally. Scholtz and Siu8 had first described the trans-sphenoidal approach for resecting primary sellar melanocytic tumors, and a series of other reports also attempted to use the same approach.2–5,7,9–11 However, the lesions are atypically firm and bloody, making complete tumor resection impossible in most cases without injury of the diaphragma sellae or cavernous sinus.11 Only two cases4,10 achieved complete surgical resection in nine trans-sphenoidal cases, and three surgeries could only take biopsies.3,8,11 Thus, some authors recommended radiotherapy of the sellar and parasellar region.2,3,7,10 In our patient, the initial trans-sphenoidal approach also failed; thus, we chose transfrontal craniotomy. Although the tumor appeared fibrous, rigid, and brownish-black (Fig. 2A), adequate surgical field exposure, bleeding control, and careful surgical operation made macroscopically complete resection possible (Fig. 2B). Other authors did not recommend routine radiotherapy after total resection.17 As illustrated herein, although the tumor recurred at the 2-year review (Fig. 2C), we suggest
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
302
R.-Y. Zhan et al.
that due to its relatively benign pathological findings it may not require adjuvant radiotherapy, and close follow-up may be an appropriate strategy after complete resection. To date, there are no treatment consensus guidelines for primary sellar melanocytic tumor, but complete surgical resection is the first recommended strategy if possible.7,17 In our opinion, transfrontal craniotomy could make complete tumor resection more feasible and safe, and the relatively benign tumor is not sensitive to radiotherapy. If complete surgical resection is achieved, clinical and MRI follow-up studies are recommended. Otherwise, stereotactic fractionated radiotherapy is indicated in most incomplete resection cases and intermediate or malignant cases. More cases should be reported to improve the treatment strategy. The prognosis of primary sellar melanocytic tumor is variable but seems to be related with benign or malignant categories and whether complete resection is performed. According to a review of the literature, half of the patients with primary sellar melanocytic tumor were alive after 2 years of follow-up (Table I), and the longest survival reported was 3.5 years.4 Our report doubles the longest survival follow-up time and provides a new treatment strategy for this disease.
Conclusions Primary sellar melanocytic tumors are exceptional lesions that are difficult to diagnose. Pathological classification and surgical resection extent may play a key role in the prognosis of these tumors. As surgical resection is often incomplete through the trans-sphenoidal approach, we suggest that the transfrontal approach achieves preferable exposure and resection once this type of lesion is suspected. Complete surgical resection may be sufficient for relatively benign lesions; otherwise, stereotactic fractionated radiotherapy is indicated. More cases should be reported to improve the treatment strategy.
Declaration financial or materials, or is supported
of interest: The authors have no personal institutional interest in any of the drugs, devices described in this article. This article by a national clinical key specialty construc-
tion projects in China and technology program of Zhejiang province (2013C33123).
References 1. Liubinas SV, Maartens N, Drummond KJ. Primary melanocytic neoplasms of the central nervous system. J Clin Neurosci 2010;17:1227–32. 2. Aubin MJ, Hardy J, Comtois R. Primary sellar haemorrhagic melanoma: case report and review of the literature. Br J Neurosurg 1997;11:80–3. 3. Chappell PM, Kelly WM, Ercius M. Primary sellar melanoma simulating hemorrhagic pituitary-adenoma: MR and pathological findings. Am J Neuroradiol 1990;11:1054–6. 4. Copeland DD, Sink JD, Seigler HF. Primary intra-cranical melanoma presenting as a suprasellar tumor. Neurosurgery 1980;6:542–5. 5. Jacob S, Pye E, Hbahbih M, Messios N, Rajabally YA. Rapidly progressive bilateral ophthalmoplegia and enlarging sellar mass caused by amelanotic melanoma. J Neuroophthalmol 2006;26:49–50. 6. Neilson JM, Moffat AD. Hypopituitarism caused by a melanoma of the pituitary gland. J Clin Pathol 1963;16:144–9. 7. Rousseau A , Bernier M, Kujas M, Varlet P. Primary intracranial melanocytic tumor simulating pituitary macroadenoma: case report and review of the literature. Neurosurgery 2005;57: E369. 8. Scholtz CL, Siu K . Melanoma of pituitary. Case report. J Neurosurg 1976;45:101–3. 9. Sidiropoulos M, Syro LV, Rotondo F, et al. Melanoma of the sellar region mimicking pituitary adenoma. Neuropathology 2013;33:175–8. 10. Tüttenberg J, Fink W, Back W, et al. A rare primary sellar melanoma. Case report. J Neurosurgery 2004;100:931–4. 11. Vezzosi D, Capuani C, Loubes-Lacroix F, et al. Primary sellar melanocytic tumor: report of new case and literature review. Pituitary 2009;12:51–6. 12. Albrecht S, Bilbao JM, Kovacs K. Non pituitary tumors of the sellar region. In: Melmed S, ed. The Pituitary, 2nd ed. Massachusetts: Black-well Publishing, 2002:592–609. 13. Hayward RD. Malignant-melanoma and central nervous-system. A guide for classification based on clinical findings. J Neurol Neurosurg Psychiatry 1976;39:526–30. 14. Jellinger K, Chou P, Paulus W. Melanocytic lesions. In: Kleihues P, Cavenee WK , eds. Pathology and Genetics of Tumours of the Nervous System: World Health Organization Classification of Tumors. Lyon: International Agency for Research on Cancer, 2000:193–195. 15. Uematsu Y, Yukawa S, Yokote H, et al. Meningeal melanocytoma: magnetic-resonance-imaging characteristics and pathological features. Case report. J Neurosurg 1992;76:705–9. 16. Barkovich AJ, Frieden IJ, Williams ML. MR of neurocutaneous melanosis. Am J Neuroradiol 1994;15:859–67. 17. Classen J, Hehr T, Paulus W, Bamberg M. Suprasellar melanocytoma: a case of primary radiotherapy and review of the literature. J Neurooncol 2002;58:39–46.
Supplementary material available online Supplemental Video. This video shows the approach of transfrontal craniotomy to resect the primary sellar giant melanocytic tumor. An initial trans-sphenoidal approach failed due to the atypically giant, hemorrhagic, and upward growing lesion, and subsequent transfrontal craniotomy was performed. The
lesion appeared fibrous, rigid, and brownish-black with rich intratumoral hemorrhage. Careful surgical operation was performed through the fi rst and second gaps, offering adequate tumor exposure and blood control, making macroscopically complete resection possible. The optic chiasm, hypothalamus, and hypophyseal stalk were completely reserved.
