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Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma.

Miller BA, Tanaka T, Ioachimescu AG, Vincentelli C, Appin CL, Oyesiku NM - J Investig Med High Impact Case Rep (2013)

Bottom Line: Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma.The patient's disease progressed despite aggressive surgical, medical and radiologic treatment.The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

View Article: PubMed Central - PubMed

Affiliation: Emory University School of Medicine, Atlanta, GA, USA.

ABSTRACT
Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS) melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient's disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

No MeSH data available.


Related in: MedlinePlus

Final magnetic resonance image after the third surgery at our institution. (A) Precontrast T1 image with bright signal typical of central nervous system melanoma. (B) Postcontrast magnetic resonance image showing extensive tumor spread.
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fig5-2324709613494008: Final magnetic resonance image after the third surgery at our institution. (A) Precontrast T1 image with bright signal typical of central nervous system melanoma. (B) Postcontrast magnetic resonance image showing extensive tumor spread.

Mentions: The patient continued to be followed in our clinic by neurosurgery, endocrinology and radiation oncology. She was maintained on cortisol and levothyroxine replacement and her ACTH levels ranged between 6 and 17 pg/mL (normal levels = 5-27 pg/mL). At age 51, she complained of double vision and facial numbness, and MRI showed progression of the tumor in the cavernous sinus and along the tentorium with compression of the right cerebral peduncle. She was initiated on carbergoline based on a case report of a silent corticotroph tumor responding to this dopamine agonist.1 One month later, MRI revealed further tumor progression, and cabergoline was discontinued. Temozolomide, which has also been shown to be effective against pituitary adenomas2 was then initiated. After 2 courses of temozolomide, the patient developed left lower extremity weakness, right facial weakness, and hearing loss. MRI showed extensive parasellar disease encasing the right internal carotid artery, entering the posterior fossa, jugular foramen, internal auditory canal, foramen magnum, and along the gyrus rectus (Figure 3A). At this point, the tumor had become hyperintense on T1 precontrast imaging. For the first time, ACTH became higher than normal (31 ng/mL). A frontotemporal craniotomy was preformed for tumor debulking. Intraoperatively, the tumor appeared dark, vascular, and friable. Pathology showed a high nuclear to cytoplasmic ratio and extensive melanin deposition, consistent with malignant melanoma (Figure 3B). Imunohistochemistry was negative for synaptophysin (Figure 3C) and positive for MITF and S100 (Figure 3D, S100 not shown), confirming the diagnosis of melanoma. The tumor at this time no longer expressed synaptophysin or pankeratin AE1/AE3, markers of pituitary adenomas that had been present in the previous 2 tumors (Figure 4). After the final surgery, the patient underwent a full dermatologic and ophthalmologic exam that showed no melanotic lesions. Postoperatively, the patient had a prolonged intensive care unit course and slow neurological recovery. Additional chemotherapy was not instituted because of the patient’s poor functional status. MRI 2 months after the final surgery showed extensive tumor progression throughout the brain and meninges that was both contrast enhancing and T1 bright, unlike the patient’s original lesion that was only contrast enhancing (Figure 5). After discussion with the family, the patient was transferred to hospice care and died at age 51.


Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma.

Miller BA, Tanaka T, Ioachimescu AG, Vincentelli C, Appin CL, Oyesiku NM - J Investig Med High Impact Case Rep (2013)

Final magnetic resonance image after the third surgery at our institution. (A) Precontrast T1 image with bright signal typical of central nervous system melanoma. (B) Postcontrast magnetic resonance image showing extensive tumor spread.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4528794&req=5

fig5-2324709613494008: Final magnetic resonance image after the third surgery at our institution. (A) Precontrast T1 image with bright signal typical of central nervous system melanoma. (B) Postcontrast magnetic resonance image showing extensive tumor spread.
Mentions: The patient continued to be followed in our clinic by neurosurgery, endocrinology and radiation oncology. She was maintained on cortisol and levothyroxine replacement and her ACTH levels ranged between 6 and 17 pg/mL (normal levels = 5-27 pg/mL). At age 51, she complained of double vision and facial numbness, and MRI showed progression of the tumor in the cavernous sinus and along the tentorium with compression of the right cerebral peduncle. She was initiated on carbergoline based on a case report of a silent corticotroph tumor responding to this dopamine agonist.1 One month later, MRI revealed further tumor progression, and cabergoline was discontinued. Temozolomide, which has also been shown to be effective against pituitary adenomas2 was then initiated. After 2 courses of temozolomide, the patient developed left lower extremity weakness, right facial weakness, and hearing loss. MRI showed extensive parasellar disease encasing the right internal carotid artery, entering the posterior fossa, jugular foramen, internal auditory canal, foramen magnum, and along the gyrus rectus (Figure 3A). At this point, the tumor had become hyperintense on T1 precontrast imaging. For the first time, ACTH became higher than normal (31 ng/mL). A frontotemporal craniotomy was preformed for tumor debulking. Intraoperatively, the tumor appeared dark, vascular, and friable. Pathology showed a high nuclear to cytoplasmic ratio and extensive melanin deposition, consistent with malignant melanoma (Figure 3B). Imunohistochemistry was negative for synaptophysin (Figure 3C) and positive for MITF and S100 (Figure 3D, S100 not shown), confirming the diagnosis of melanoma. The tumor at this time no longer expressed synaptophysin or pankeratin AE1/AE3, markers of pituitary adenomas that had been present in the previous 2 tumors (Figure 4). After the final surgery, the patient underwent a full dermatologic and ophthalmologic exam that showed no melanotic lesions. Postoperatively, the patient had a prolonged intensive care unit course and slow neurological recovery. Additional chemotherapy was not instituted because of the patient’s poor functional status. MRI 2 months after the final surgery showed extensive tumor progression throughout the brain and meninges that was both contrast enhancing and T1 bright, unlike the patient’s original lesion that was only contrast enhancing (Figure 5). After discussion with the family, the patient was transferred to hospice care and died at age 51.

Bottom Line: Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma.The patient's disease progressed despite aggressive surgical, medical and radiologic treatment.The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

View Article: PubMed Central - PubMed

Affiliation: Emory University School of Medicine, Atlanta, GA, USA.

ABSTRACT
Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS) melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient's disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

No MeSH data available.


Related in: MedlinePlus