A Rare Case of Metastatic Transformation to Pituitary Carcinoma

Abstract Background: Pituitary carcinomas are rare and comprise less than 0.5% of pituitary tumors and frequently arise from previously resected and/or radiated infiltrating adenomas.1 Radiation therapy is used to prevent regrowth but does not have significant data supporting improved prognosis.2 True pituitary carcinomas requires the presence of craniospinal and/or systemic metastases. Here, we present a case of benign pituitary adenoma that had progressed to a metastatic tumor and responded to radiation therapy. Clinical Case: Our patient was first diagnosed in 1982 with a pituitary mass after undergoing an MRI due to right eye blindness. He ultimately had a transcranial resection of the tumor and post-operative external radiation to residual tumor. Final pathology was consistent with a nonsecretory tumor. Additionally, he was diagnosed with panhypopituitarism and he was treated accordingly. Due to barriers of patient adherence, only one post-operative MRI was obtained, and he was lost to endocrine follow up. In 2007, he was again referred to endocrinology for new vision loss in the left eye. An MRI revealed a 3.0 x 3.8 x 4.4 cm tumor that compressed the optic chiasm. Additionally, multiple lesions were seen within the dural and leptomeningeal extra-axial areas including the largest left frontal lesion of 2.4 cm and a 1.7 cm lesion posterior to the cord within the foramen magnum. The patient underwent endonasal transsphenoidal resection of the sellar mass and biopsy of the frontal lesion in October 2007. Pathology showed pituitary adenocarcinoma in both the sellar and frontal lesions and immunoperoxidase staining was negative for all hormones. He completed salvage radiation to the sellar and craniospinal lesions in December 2007. MRI scans completed 7 months later showed stable residual pituitary and metastatic lesions. The patient received 6-month MRI screening exams for the first 2 years and then annually thereafter, as well as PET scanning, without significant progression or new metastatic lesions. Conclusion: We present a case of benign pituitary adenoma which transformed following resection to a malignant tumor with metastatic lesions in the brain and spinal cord that was treated with radiation with relative success. Despite the often-aggressive nature of these metastatic tumors, the patient has experienced a successful treatment course with minimal side effects and without progression 13 years after initial treatment of the metastatic pituitary carcinoma.

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Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

Case Reports in Oncological Medicine ◽

10.1155/2015/810367 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Clarissa Groberio Borba ◽

Rafael Loch Batista ◽

Nina Rosa de Castro Musolino ◽

Vanielle Carvalho Machado ◽

Ana Elisa Evangelista Alcantara ◽

...

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Disease ◽

Adrenocorticotropic Hormone ◽

Pituitary Carcinoma ◽

Cushing's Disease ◽

Resonance Imaging ◽

Ki 67 ◽

P53 Expression ◽

Acth Secreting ◽

Pituitary Carcinomas

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

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Metastatic prolactinoma: case report with immunohistochemical assessment for p53 and Ki-67 antigens

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000500029 ◽

2005 ◽

Vol 63 (3b) ◽

pp. 864-869 ◽

Cited By ~ 1

Author(s):

Paulo S. Crusius ◽

Cassiano M. Forcelini ◽

Adroaldo B. Mallmann ◽

Daniela A. Silveira ◽

Elder Lersch ◽

...

Keyword(s):

Radiation Therapy ◽

Case Report ◽

Pituitary Adenoma ◽

Fatal Outcome ◽

Proliferative Index ◽

Ki 67 ◽

Rare Finding ◽

Intracranial Metastases ◽

Immunohistochemical Assessment ◽

Pituitary Carcinomas

Pituitary carcinomas are rare neoplasms characterized by craniospinal and/or systemic metastases originated from the pituitary. Their histopathology is frequently indistinguishable from that of benign adenomas. The development of markers that better reflect their behavior is desirable. We present the case of a 47 year-old man with a prolactin-secreting macroadenoma who was submitted to surgeries, cranial radiation therapy, and bromocriptine treatment, but evolved to a fatal outcome after the disclosure of intracranial metastases. Tumor samples underwent p53 and Ki-67 immunohistochemical assessment. p53 was absent in all samples, a rare finding among pituitary carcinomas. Ki-67 proliferative index was 2.80% in the original tumor, 4.40% in the relapse, and 4.45% in the metastasis. The figure in the relapse is higher than the expected for a noninvasive adenoma. In conclusion, p53 staining is not positive in all pituitary carcinomas. A high Ki-67 proliferative index in a pituitary adenoma might indicate a more aggressive behavior.

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Pituitary Carcinoma with Subependymal Spread

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100005254 ◽

2006 ◽

Vol 33 (3) ◽

pp. 329-332

Author(s):

Krishna Kumar ◽

Jefferson R. Wilson ◽

Qiuyan Li ◽

Ryan Phillipson

Keyword(s):

Pituitary Adenomas ◽

Latency Period ◽

Pituitary Tumors ◽

Pituitary Carcinoma ◽

First Year ◽

Cervical Lymph Nodes ◽

Metastatic Lesions ◽

Systemic Spread ◽

Invasive Carcinomas ◽

Pituitary Carcinomas

Pituitary carcinomas have been reported to metastasize systemically and, less commonly, along the craniospinal axis. Metastatic lesions have been reported in the cerebral cortex, cerebellum, spinal cord, leptomeninges, cervical lymph nodes, liver, ovaries, and bone. The authors are unaware of any other examples of subependymal metastases of a pituitary carcinoma. We report such a case.Pituitary carcinoma is rare, accounting for roughly 0.2%1,3-5 of all pituitary tumors, with approximately 140 cases reported in the literature. These tumors are associated with a very high mortality, with 66% of patients dying within the first year after diagnosis. Pituitary carcinomas are differentiated from invasive pituitary adenomas by the presence of non-contiguous craniospinal tumor deposits and/or distant systemic metastases. The majority (88%) of these carcinomas prove to be hormone secreting, with prolactin secreting tumors being the most common. Invasive carcinomas evolve from hormone secreting pituitary adenomas after a latency period. Pituitary carcinomas have a predilection for systemic spread. The rate of systemic metastasis approaches 71% for prolactin producing tumors and 57% for ACTH producing tumors. Thirteen percent of tumors demonstrate both systemic and craniospinal patterns of metastatic spread.

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Stereotactic Body Radiation Therapy (SBRT) for a Patient with a Myocardial Metastasis: A Case Report

Current Oncology ◽

10.3390/curroncol28010041 ◽

2021 ◽

Vol 28 (1) ◽

pp. 390-395

Author(s):

Aneesh Dhar ◽

Elysia Donovan ◽

Darryl Leong ◽

Sebastien J. Hotte ◽

Anand Swaminath

Keyword(s):

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Mri Scan ◽

Distant Disease ◽

Cardiac Lesion ◽

Stereotactic Body Radiation ◽

Metastatic Lesions ◽

Cardiac Symptoms ◽

Myocardial Metastasis ◽

Magnetic Resonance Imaging Mri

Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient’s cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion.

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Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01347 ◽

2018 ◽

Vol 103 (10) ◽

pp. 3925-3930 ◽

Cited By ~ 37

Author(s):

Andrew L Lin ◽

Philip Jonsson ◽

Viviane Tabar ◽

T Jonathan Yang ◽

John Cuaron ◽

...

Keyword(s):

Pituitary Adenoma ◽

Liver Metastasis ◽

Effective Treatment ◽

Somatic Hypermutation ◽

Treatment Options ◽

Pituitary Tumors ◽

Pituitary Carcinoma ◽

Tumor Resistance ◽

Clinical Sequencing ◽

Acth Secreting

Abstract Context Pituitary carcinoma is a rare and aggressive malignancy with a poor prognosis and few effective treatment options. Case A 35-year-old woman presented with an aggressive ACTH-secreting pituitary adenoma that initially responded to concurrent temozolomide and capecitabine prior to metastasizing to the liver. Following treatment with ipilimumab and nivolumab, the tumor volume of the dominant liver metastasis reduced by 92%, and the recurrent intracranial disease regressed by 59%. Simultaneously, her plasma ACTH level decreased from 45,550 pg/mL to 66 pg/mL. Molecular Evaluation Both prospective clinical sequencing with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets and retrospective whole-exome sequencing were performed to characterize the molecular alterations in the chemotherapy-naive pituitary adenoma and the temozolomide-resistant liver metastasis. The liver metastasis harbored a somatic mutational burden consistent with alkylator-induced hypermutation that was absent from the treatment-naive tumor. Resistance to temozolomide treatment, acquisition of new oncogenic drivers, and subsequent sensitivity to immunotherapy may be attributed to hypermutation. Conclusion Combination treatment with ipilimumab and nivolumab may be an effective treatment in pituitary carcinoma. Clinical sequencing of pituitary tumors that have relapsed following treatment with conventional chemotherapy may identify the development of therapy-induced somatic hypermutation, which may be associated with treatment response to immunotherapy.

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LOCKED-IN SYNDROME DUE TO MULTIPLE BRAIN STEM INFARCTIONS AND FOCI OF DEMYELINATION AFTER RADIATION THERAPY OF PITUITARY ADENOMA WITH ACROMEGALY

The Scientific Notes of the I P Pavlov St Petersburg State Medical University ◽

10.24884/1607-4181-2018-25-3-89-95 ◽

2018 ◽

Vol 25 (3) ◽

pp. 89-95

Author(s):

L. G. Zaslavskii ◽

E. A. Skorniakova ◽

O. L. Zaslavskaia ◽

S. G. Feofanova ◽

E. A. Lomteva ◽

...

Keyword(s):

Radiation Therapy ◽

Pituitary Adenoma ◽

Brain Stem ◽

Vascular Wall ◽

Pulse Therapy ◽

Focal Lesion ◽

Homozygous Mutation ◽

Respiratory Disturbance ◽

The Brain ◽

Multiple Cerebral Infarctions

Locked-in syndrome (LIS) is a rare neurological disorder, usually appears as a result of the pons cerebellar damage, mostly after the brain stroke. Locked-in syndrome is characterized by the paralysis of skeletal muscles (respiratory, facial, pharyngeal, lingual and muscles of the extremities). Patient is unable to speak and breath, facial expressions and voluntary movements are also impossible. Acromegaly is a disease that can be described by the increase of the growth hormone (GH) and Insulin-like growth factor (IGF-1) and develops in most cases due to the pituitary adenomas. Pituitary adenoma (PA) can be treated by neurosurgical techniques, pharmaceutical and radiation therapy (RT). We present a clinical case of 33-year-old woman with PA-caused acromegaly, that developed muscle weakness, nausea, vomit and respiratory disturbance in a 2 months after the radiation therapy. Subacute comatose state was developed in the patient. MRI of the brain revealed a multi-focal lesion of the media-basal regions on both sides, frontal corpus callosum and brain stem. Differential diagnosis included an acute demyelination (SD, PML), viral encephalitis and vasculitis. Treatment included methylprednisolone pulse therapy and plasmapheresis. The consciousness cleared up, but there was no spontaneous breathing, tetraplegia persisted. Autoimmune and infectious diseases was excluded. The homozygous mutation PAI-1-675 4G/4G was found. In this case, acromegaly induced endothelial dysfunction was the pathogenesis factor of multiple cerebral infarctions and demyelinating lesions, as well as RT and its proven pathological influence on the vascular wall and the fibrinolytic system. The revealed thrombophilia was also a factor of multiple cerebral infarctions. A Potential combination of pathogenic factors in the development of cerebral should be taken into account in predicting complications of RT.

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ARTO trial (NCT03449719), a randomized phase II trial enrolling oligometastatic castration-resistant prostate cancer patients treated with first-line abiraterone acetate with or without stereotactic body radiation therapy: Preliminary results comprehensive of biochemical outcomes and circulating tumor cells analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.118 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 118-118

Author(s):

Giulio Francolini ◽

Pietro Garlatti ◽

Mauro Loi ◽

Beatrice Detti ◽

Michele Aquilano ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Receptor ◽

Adverse Events ◽

Phase Ii Trial ◽

Abiraterone Acetate ◽

Metastatic Lesions ◽

Randomized Phase Ii ◽

And Control ◽

Psma Expression

118 Background: Androgen Receptor Targeted Agents (ARTA) represent one of the main treatment options for metastatic castrate resistant prostate cancer (mCRPC). Addition of stereotactic radiation therapy (SBRT) to ablate metastatic foci may improve clinical outcomes in oligometastatic setting. ARTO trial (NCT03449719) is a randomized phase II trial testing the benefit of upfront SBRT on all sites of metastatic disease in oligo-mCRPC patients undergoing I line therapy with Abiraterone Acetate (AA). In this preliminary analysis, we report results after 6 months of follow up, together with an exploratory analysis of androgen receptor splice variants (ARV7/ARFL) Prostate Specific Antigen (PSA) and Prostate Specific Membrane Antigen (PSMA) expression on Circulating Tumor Cells (CTCs) detected in this cohort of patients. Methods: 31 patients affected by oligo-mCRPC (defined as < 3 non-visceral metastatic lesions) were randomized to receive I line AA therapy with or without SBRT on all metastatic sites. Baseline blood samples to detect CTCs and evaluate their ARV7, ARFL, PSA and PSMA expression were taken before AA treatment start. Assessments comprehensive of clinical examination and serum PSA were performed every three months. Toxicity was assessed by the Common Terminology Criteria for Adverse Events toxicity scale (CTCAE v.4.03). Results: Thirteen and 18 patients were enrolled in the treatment and control arm, respectively. Nineteen metastatic lesions were treated with SBRT in the treatment arm. At 6 months, complete response (defined as a serum PSA level < 0.2 ng/dl) and biochemical response (defined as a PSA reduction > 50% if compared to baseline) were achieved in 6 vs 4 and in 10 vs 8 patients in the treatment vs control arm, respectively. One patient in the treatment arm died for other causes, 1 biochemical progression occurred in the control arm. No adverse events occurred in both arms of treatment. CTCs analysis was available for 10 patients, out of whom 4 were found positive for CTCs (1 and 3 from the treatment and control arm, respectively). ARV7 and ARFL were expressed in 1 patient from the control arm, PSMA was expressed in all CTC positive patients, PSA was expressed in 2 patients from the control and one from the treatment arm. Conclusions: SBRT+AA in oligo-mCRPC patients was safe and yielded promising biochemical results. CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients. Data about ARV7, ARFL, PSA and PSMA expression represent an interesting snapshot of biomarker arrangement in this setting. Clinical trial information: NCT03449719.

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