CASE REPORTS IN GI ONCOLOGY
Metastatic Colon Cancer Presenting as Pituitary Mass Danny Issa,1 Swapna Thota,1 Timothy Spiro,2 Hamed Daw,2 Andres Chiesa,3 Abdo Haddad2 1 Department of Internal Medicine, Fairview Hospital 2 Department of Regional Oncology 3 Department of Anatomic Pathology Cleveland Clinic Cleveland OH © 2013 by International Society of Gastrointestinal Oncology
CASE REPORT A 56-year-old Caucasian female presented with complaints of headache and impaired vision in the left eye. Her oncologic history was significant for stage III adenocarcinoma of the colon diagnosed 4.5 years before presentation (Figure 1A). At that time she underwent left hemicolectomy and adjuvant chemotherapy with a single
agent, 5-fluorouracil (FU), and refused oxaliplatin. Chemotherapy was stopped after two cycles, because of side effects—mainly, mucositis and diarrhea. After 4.5 years, the patient presented with complaints of diffuse headache for 1 month and a gradual loss of vision in the left eye. On examination, she was found to have left temporal hemianopsia without evidence of any other cranial nerve
Figure 1. (A) A Metastatic colonic adenocarcinoma characterized by glands lined by tall columnar cells with penicillate nuclei with associated necrosis (hematoxylin and eosin; ⫻40). (B) Immunohistochemical stain for cytokeratin 20 shows strong positivity within most of thetumor cells (⫻40). (C) Immunohistochemical stain for CDX-2 shows strong nuclear positivity (⫻100). (D) MRI of the brain reveals a pituitary mass.
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Case Reports in GI Oncology
palsies. Her motor and sensory examination was within normal limits. Initial laboratory analysis revealed severe hyponatremia with sodium of 117 mEq/L, and further work-up revealed central hypothyroidism as the cause of the hyponatremia. Laboratory values showed thyroid-stimulating hormone (TSH) of 0.05 U/mL (range, 0.400 –5.500) and free T4 of 0.34 ng/dL (0.7–1.8), with normal values for the remaining endocrinologic work-up. The carcinoembryonic antigen (CEA) tumor marker was 156.4 ng/mL. No previous measurement of CEA was available for comparison. MRI of the brain revealed a 3.4 ⫻ 2.8-cm pituitary mass extending bilaterally into the cavernous sinuses and into the suprasellar cistern vertically (Figure 1D). The mass also abutted the optic nerve. Given the patient’s medical history, worsening pressure symptoms from the tumor, and the nature of tumor extension, a multidisciplinary tumor board team made the decision to pursue surgical removal of the pituitary mass. A transnasal/transsphenoidal resection of the tumor was performed. Pathology of the tumor showed positive staining with antibodies to cytokeratin 20 (Figure 1B) and CDX-2 (Figure 1C), consistent with a colorectal origin of the metastatic tumor. Subsequent staging revealed distant metastases involving retroperitoneal lymph nodes, liver, and lungs. A K-ras mutation was detected. Treatment was initiated with levothyroxine and local therapy by gamma knife radiation therapy to the sella turcica with corticosteroids, which partially improved the patient’s vision. She then received palliative systemic therapy with 5-FU, folinic acid, and irinotecan (FOLFIRI) and bevacizumab for 10 cycles. Because of disease progression, chemotherapy was switched to oral capecitabine. The patient declined further intravenous chemotherapy. After 3 months and further progression of the disease systemically, the treatment was discontinued. The patient declined further chemotherapy and was enrolled in hospice care. The time from presentation to hospice referral was 17.5 months.
DISCUSSION Colorectal cancer (CRC) is the second leading cause of cancerrelated deaths in the United States. One in 5 patients with colorectal cancer have distant metastatic disease at the time of presentation.1 Lymphatic and hematogenous disseminations are the main routes of cancer spread, in addition to contiguous and transperitoneal routes. The venous drainage of the colon goes through the portal system; hence, the first site of hematogenous dissemination is usually the liver, followed by the lungs, bone, and many other sites, including the brain. The incidence of brain metastasis from colorectal cancer is low— estimated to be approximately 2.3% of all patients with metastatic CRC.2 Most of the brain metastases are located in the cerebellum and less frequently in the frontal, temporal, parietal, and occipital lobes.2 The pituitary gland is an uncommon site of metastasis, with only a handful of cases reported to be of colonic origin3,4 (Table 1). Diagnosis and management of pituitary metastasis (PM) can be challenging and requires a multidisciplinary team approach that includes gastroenterologists, oncologists, and endocrinologists. PMs have nonspecific clinical features and are not easily distinguishable from other benign primary pituitary tumors by hormonal September–December 2013
Table 1 Case reports of PM from colon cancer in the past two decades Year reported
Primary cancer
Tomita et al5
2000
Colon
Subarachnoid hemorrhage
Neromi et al6
1999
Colon
Bitemporal hemianopsia
Nimura et al7
1998
Colon
Diabetes insipidus
Stalldecker et al8
1994
Colon
Panhypopituitarism
Author
Predominant feature
assays or imaging modalities.4 Unlike pituitary adenoma, a diagnosis of PM is established by histopathology. A strong clinical suspicion becomes the cornerstone of pursuing a work-up to establish the diagnosis. PMs carry a poor prognosis, as they are usually associated with a significant burden of metastatic disease. In the following sections, we review the limited literature available about this rare clinical condition.
Epidemiology Metastasis to the pituitary gland is rare.3–4 It was first described by Benjamin in 1857.5 Large autopsy series have reported an incidence of 1.0 –3.6% of PM in patients with malignancies.3,4,9,10 Several of the malignancies appear to metastasize more frequently to the pituitary, such as breast cancer in females and lung cancer in males. In two retrospective studies, PMs of colonic origin contributed to 2–3% of the cases.11,12 Owing to its rarity, there is a lack of large-sample prospective studies to help in understanding the mechanism or progression of the disease.
Pathogenesis and Clinical Features PMs are mostly identified in the setting of a disseminated metastatic disease.3,4,9–11 The most common route of metastasis to the pituitary is via the blood stream. It is postulated that the tumor seeding often begins at the posterior pituitary because of the direct blood supply from the systemic circulation. The involvement of the anterior pituitary, supplied by the portal system, is less direct and occurs via direct invasion of the posterior pituitary tumor.5 Hence, symptoms related to anterior pituitary involvement typically occur late in the disease course and are seldom seen without the involvement of the posterior pituitary.3–13 Patients with symptomatic PMs often present with fast growing tumors that involve the posterior pituitary and manifest with symptoms of posterior pituitary dysfunction, such as diabetes insipidus. However, if the tumor is slow growing, the initial findings may go unnoticed and the patients may present later with anterior pituitary insufficiency or manifestations related to invasion of the pituitary stalk and optic chiasm14,15—a possible explanation of the visual disturbance and central hypothyroidism found in our patient.
Clinical Features Symptoms of PM are reported in approximately18% of cases. Many patients have widely disseminated cancer at presentation, and the www.myGCRonline.org
153
Case Reports in GI Oncology
systemic manifestations of the tumors may mask the symptoms of PMs.12 The most common clinical manifestations of PM are4: • Central diabetes insipidus (30 – 60%),3,4,9–12 by far the most common presenting symptom. It involves the posterior lobe after invasion of the infundibulum or hypothalamus. Patients are usually mildly symptomatic with polyuria, nocturia, and polydipsia. However, if the thirst mechanism is impaired, the manifestations become severe, leading to signs of dehydration and hypernatremia. • Pan hypopituitarism (7– 47%).3,4,9–12 The diagnosis in this case is most commonly disclosed by development of new-onset hypocortisolism and/or central hypothyroidism. Presentation with hyperprolactinemia has been described as well. It should be noted that both hypocortisolism and hypothyroidism are late manifestations of pituitary failure, and hence disease is usually advanced at this stage. • Retro-orbital pain and headache (0 – 40%), most likely caused by meningeal irritation, or rarely, by increased intracranial pressure from apoplexy of sellar metastasis.16 • Ophthalmoplegia (15– 43%), due to extension into the cavernous sinus of a very large tumor or in rare instances, pituitary apoplexy.17 The most commonly involved cranial nerves are III and IV. The combination leads to various degrees of ophthalmoplegia. • Visual field deficits (7–33%), the most common being bitemporal hemianopsia from invasion of the optic chiasm. Other less common manifestations include altered mental status, seizures, and eating disorders.5–8,12–17 These findings are not specific for metastatic cancer. Primary pituitary tumors such as pituitary adenomas may present similarly. However, the development of new-onset diabetes insipidus in any patient with known metastatic cancer should prompt a physician to look for PMs. Imaging Currently, it is not possible to differentiate PM from pituitary adenoma solely on the basis of radiographic appearance. However, certain characteristics have been described more commonly in PM, including (1) a computed tomographic (CT) scan revealing a sellar mass causing erosion of the sellar floor without causing sellar enlargement; (2) magnetic resonance imaging (MRI) findings of a dumbbell-shaped sellar mass with a clear margin at the diaphragm level, best seen on a sagittal image,17,18 and loss of-high intensity signals of the posterior pituitary in T1 weighed images; (3) angiography (if done), typically revealing significant tumor staining reflecting high vascularity.19 None of these radiologic findings are sufficiently specific for PM; similar patterns may be present in primary pituitary tumors. Diagnosis The diagnosis is based on histology because of the paucity of specific clinical and radiologic findings. A transsphenoidal biopsy for diagnosis has been considered very infrequently because of the mimicry between metastatic tumors and pituitary adenomas. The latter require a complete excision. Hence, the current means of
154
Gastrointestinal Cancer Research
establishing diagnosis is by transsphenoidal excision of the tumor.17–20 Not uncommonly, the diagnosis is established only at autopsy. Prognosis and Management The prognosis is uniformly poor, with mean survival between 6 and 22 months.4,9–12 Therefore, management should be directed at treatment of the primary cancer; local treatment with surgery, radiation, or both; and palliation of symptoms. Surgery and radiation therapy have typically been used, whereas the role of chemotherapy is unclear, but it may help if the primary tumor is sensitive to treatment. The role of surgery (ie, transsphenoidal resection) may be limited to palliation of significant symptoms, such as vision loss and ophthalmoplegia, and may be avoided otherwise, unless it is needed to establish the diagnosis in unclear cases. Radiation treatment is an option for most of the patients who present with endocrinologic disturbances. Recently gamma knife stereotactic surgery has emerged as a potential therapeutic option.21 It has been a matter of debate whether whole-brain irradiation or limited-field radiation is optimal for these patients,4 because of the lack of sufficient data from the rarity of the disease itself. However, both surgery and radiation have been shown to improve the quality of life without significantly improving survival.12 It should also be noted that there is a significant role for endocrine treatments such as supplemental corticosteroids for patients with hypocortisolism, thyroid hormones for hypothyroidism, and desmopressin or carbamazepine for central diabetes insipidus. Since the clinical features of the former two conditions resemble depression, which is very common in this population, the diagnosis may be delayed unless it is actively sought. Similarly, the oral intake of these patients is typically poor, leading to dehydration and hypernatremia, which may disguise the underlying cause of central diabetes insipidus. Hence, consideration of pituitary involvement in the differential diagnoses would be prudent in any patient with disseminated cancer presenting with these symptoms.
CONCLUSIONS Rarely, colon cancer recurs in uncommon sites such as the pituitary gland. PM presents in the setting of disseminated metastatic disease and remains an uncommon clinical condition. The representative patient population for this diagnosis is known to have metastatic cancer and presents with posterior or anterior pituitary failure. The incidence of brain metastasis in colon cancer is expected to increase because of the increased survival of patients with this malignancy.2 If clinical suspicion is high for metastasis, benefits from aggressive measures must be weighed against the risks of compromising quality of life, given the absence of documented survival benefit with any therapeutic measures. Palliative chemotherapy and targeted therapy for colon cancer have been effective in controlling systemic disease and prolonging overall survival of metastatic colon cancer. Both surgery and radiation treatments are palliative. Management of coexistent endocrine abnormalities is important and has a significant role in maintaining the quality of life in these terminally ill patients. A multidisciplinary team approach is also important in the management of this rare complication of colon cancer. Volume 6 • Issue 5– 6
Case Reports in GI Oncology REFERENCES 1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 62:10 –29, 2012 2. Mongan JP, Fadul CE, Cole BF, et al: Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. Clin Colorectal Cancer 8:100 –105, 2009 3. Max MB, Deck MD, Rottenberg DA: Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 31: 998 –1002, 1981 4. Fassett DR, Couldwell WT: Metastases to the pituitary gland. Neurosurg Focus 16:998 –E8, 2004 5. Tomita H, Urui S, Kokunai T, et al: A case of metastatic tumor of the pituitary gland presenting as a subarachnoid hemorrhage (in Japanese). No Shinkei Geka 28:1117–20, 2000 6. Neroni M, Artico M, Pastore FS, et al: Diaphragma sellae metastasis from colon carcinoma mimicking a meningioma: a case report. Neurochirurgie 45:160 –163, 1999 7. Nimura Taro OT, Goto Hideki, et al: Magnetic Resonance Imaging Characteristics of Pituitary Metastasis from Colon Cancer Associated with Diabetes Insipidus: A Case Report. Progress in Computed Imaging 1998 8. Stalldecker G, Molina HA, Antelo N, et al: Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis (in Spanish). Medicina (B Aires) 54:248 –52, 1994 9. Benjamin L: Ein Krebsfall. Virchows Archiv Pathol Anat 12:248 –561, 1857 10. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 3:74 – 85, 1950 11. Teears RJ, Silverman EM: Clinicopathologic review of 88 cases of carcinoma metastatic to the pituitary gland. Cancer 36:216 –20, 1975 12. Morita A, Meyer FB, Laws ER, Jr: Symptomatic pituitary metastases. J Neurosurg 89:69 –73, 1998 13. Houck WA, Olson KB, Horton J: Clinical features of tumor metastasis to the pituitary. Cancer 26:656 –9, 1970
September–December 2013
14. Nishio S, Tsukamoto H, Fukui M, et al: Hypophyseal metastatic hypernephroma mimicking a pituitary adenoma: case report. Neurosurg Rev 15: 319 –22 15. Cox EV 3rd: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:49 –50, 1979 16. Chhiber SS, Bhat AR, Khan SH, et al: Apoplexy in sellar metastasis: a case report and review of literature. Turk Neurosurg 21:230 –234, 2011 17. Komninos J, Vlassopoulou V, Protopapa D, et al: Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 89:574 –580, 2004 18. Mao JF, Zhang JL, Nie M, et al: Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: clinical presentations, diagnosis, and management. J Postgrad Med 57:302– 6, 2011 19. Yokoyama T, Yoshino A, Katayama Y, et al: Metastatic pituitary tumor from renal cell carcinoma treated by fractionated stereotactic radiotherapy: case report. Neurol Med Chir (Tokyo) 44:47–52, 2004 20. McCormick PC, Post KD, Kandji AD, et al: Metastatic carcinoma to the pituitary gland. Br J Neurosurg 3:71–79, 1989 21. Mori Y, Kobayashi T, Shibamoto Y. Stereotactic radiosurgery for metastatic tumors in the pituitary gland and the cavernous sinus. J Neurosurg 105(Suppl):37– 42, 2006
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Danny Issa, MD, Department of Internal Medicine, Fairview Hospital Cleveland Clinic, 18101 Lorain Road, Cleveland, OH 44111. Phone: (216) 476-7029 or (216)-476-7078; Fax: (216) 476-2944; E-mail: [email protected]
www.myGCRonline.org
155
Metastatic Colon Cancer Presenting as Pituitary Mass Danny Issa,1 Swapna Thota,1 Timothy Spiro,2 Hamed Daw,2 Andres Chiesa,3 Abdo Haddad2 1 Department of Internal Medicine, Fairview Hospital 2 Department of Regional Oncology 3 Department of Anatomic Pathology Cleveland Clinic Cleveland OH © 2013 by International Society of Gastrointestinal Oncology
CASE REPORT A 56-year-old Caucasian female presented with complaints of headache and impaired vision in the left eye. Her oncologic history was significant for stage III adenocarcinoma of the colon diagnosed 4.5 years before presentation (Figure 1A). At that time she underwent left hemicolectomy and adjuvant chemotherapy with a single
agent, 5-fluorouracil (FU), and refused oxaliplatin. Chemotherapy was stopped after two cycles, because of side effects—mainly, mucositis and diarrhea. After 4.5 years, the patient presented with complaints of diffuse headache for 1 month and a gradual loss of vision in the left eye. On examination, she was found to have left temporal hemianopsia without evidence of any other cranial nerve
Figure 1. (A) A Metastatic colonic adenocarcinoma characterized by glands lined by tall columnar cells with penicillate nuclei with associated necrosis (hematoxylin and eosin; ⫻40). (B) Immunohistochemical stain for cytokeratin 20 shows strong positivity within most of thetumor cells (⫻40). (C) Immunohistochemical stain for CDX-2 shows strong nuclear positivity (⫻100). (D) MRI of the brain reveals a pituitary mass.
152
Gastrointestinal Cancer Research
Volume 6 • Issue 5– 6
Case Reports in GI Oncology
palsies. Her motor and sensory examination was within normal limits. Initial laboratory analysis revealed severe hyponatremia with sodium of 117 mEq/L, and further work-up revealed central hypothyroidism as the cause of the hyponatremia. Laboratory values showed thyroid-stimulating hormone (TSH) of 0.05 U/mL (range, 0.400 –5.500) and free T4 of 0.34 ng/dL (0.7–1.8), with normal values for the remaining endocrinologic work-up. The carcinoembryonic antigen (CEA) tumor marker was 156.4 ng/mL. No previous measurement of CEA was available for comparison. MRI of the brain revealed a 3.4 ⫻ 2.8-cm pituitary mass extending bilaterally into the cavernous sinuses and into the suprasellar cistern vertically (Figure 1D). The mass also abutted the optic nerve. Given the patient’s medical history, worsening pressure symptoms from the tumor, and the nature of tumor extension, a multidisciplinary tumor board team made the decision to pursue surgical removal of the pituitary mass. A transnasal/transsphenoidal resection of the tumor was performed. Pathology of the tumor showed positive staining with antibodies to cytokeratin 20 (Figure 1B) and CDX-2 (Figure 1C), consistent with a colorectal origin of the metastatic tumor. Subsequent staging revealed distant metastases involving retroperitoneal lymph nodes, liver, and lungs. A K-ras mutation was detected. Treatment was initiated with levothyroxine and local therapy by gamma knife radiation therapy to the sella turcica with corticosteroids, which partially improved the patient’s vision. She then received palliative systemic therapy with 5-FU, folinic acid, and irinotecan (FOLFIRI) and bevacizumab for 10 cycles. Because of disease progression, chemotherapy was switched to oral capecitabine. The patient declined further intravenous chemotherapy. After 3 months and further progression of the disease systemically, the treatment was discontinued. The patient declined further chemotherapy and was enrolled in hospice care. The time from presentation to hospice referral was 17.5 months.
DISCUSSION Colorectal cancer (CRC) is the second leading cause of cancerrelated deaths in the United States. One in 5 patients with colorectal cancer have distant metastatic disease at the time of presentation.1 Lymphatic and hematogenous disseminations are the main routes of cancer spread, in addition to contiguous and transperitoneal routes. The venous drainage of the colon goes through the portal system; hence, the first site of hematogenous dissemination is usually the liver, followed by the lungs, bone, and many other sites, including the brain. The incidence of brain metastasis from colorectal cancer is low— estimated to be approximately 2.3% of all patients with metastatic CRC.2 Most of the brain metastases are located in the cerebellum and less frequently in the frontal, temporal, parietal, and occipital lobes.2 The pituitary gland is an uncommon site of metastasis, with only a handful of cases reported to be of colonic origin3,4 (Table 1). Diagnosis and management of pituitary metastasis (PM) can be challenging and requires a multidisciplinary team approach that includes gastroenterologists, oncologists, and endocrinologists. PMs have nonspecific clinical features and are not easily distinguishable from other benign primary pituitary tumors by hormonal September–December 2013
Table 1 Case reports of PM from colon cancer in the past two decades Year reported
Primary cancer
Tomita et al5
2000
Colon
Subarachnoid hemorrhage
Neromi et al6
1999
Colon
Bitemporal hemianopsia
Nimura et al7
1998
Colon
Diabetes insipidus
Stalldecker et al8
1994
Colon
Panhypopituitarism
Author
Predominant feature
assays or imaging modalities.4 Unlike pituitary adenoma, a diagnosis of PM is established by histopathology. A strong clinical suspicion becomes the cornerstone of pursuing a work-up to establish the diagnosis. PMs carry a poor prognosis, as they are usually associated with a significant burden of metastatic disease. In the following sections, we review the limited literature available about this rare clinical condition.
Epidemiology Metastasis to the pituitary gland is rare.3–4 It was first described by Benjamin in 1857.5 Large autopsy series have reported an incidence of 1.0 –3.6% of PM in patients with malignancies.3,4,9,10 Several of the malignancies appear to metastasize more frequently to the pituitary, such as breast cancer in females and lung cancer in males. In two retrospective studies, PMs of colonic origin contributed to 2–3% of the cases.11,12 Owing to its rarity, there is a lack of large-sample prospective studies to help in understanding the mechanism or progression of the disease.
Pathogenesis and Clinical Features PMs are mostly identified in the setting of a disseminated metastatic disease.3,4,9–11 The most common route of metastasis to the pituitary is via the blood stream. It is postulated that the tumor seeding often begins at the posterior pituitary because of the direct blood supply from the systemic circulation. The involvement of the anterior pituitary, supplied by the portal system, is less direct and occurs via direct invasion of the posterior pituitary tumor.5 Hence, symptoms related to anterior pituitary involvement typically occur late in the disease course and are seldom seen without the involvement of the posterior pituitary.3–13 Patients with symptomatic PMs often present with fast growing tumors that involve the posterior pituitary and manifest with symptoms of posterior pituitary dysfunction, such as diabetes insipidus. However, if the tumor is slow growing, the initial findings may go unnoticed and the patients may present later with anterior pituitary insufficiency or manifestations related to invasion of the pituitary stalk and optic chiasm14,15—a possible explanation of the visual disturbance and central hypothyroidism found in our patient.
Clinical Features Symptoms of PM are reported in approximately18% of cases. Many patients have widely disseminated cancer at presentation, and the www.myGCRonline.org
153
Case Reports in GI Oncology
systemic manifestations of the tumors may mask the symptoms of PMs.12 The most common clinical manifestations of PM are4: • Central diabetes insipidus (30 – 60%),3,4,9–12 by far the most common presenting symptom. It involves the posterior lobe after invasion of the infundibulum or hypothalamus. Patients are usually mildly symptomatic with polyuria, nocturia, and polydipsia. However, if the thirst mechanism is impaired, the manifestations become severe, leading to signs of dehydration and hypernatremia. • Pan hypopituitarism (7– 47%).3,4,9–12 The diagnosis in this case is most commonly disclosed by development of new-onset hypocortisolism and/or central hypothyroidism. Presentation with hyperprolactinemia has been described as well. It should be noted that both hypocortisolism and hypothyroidism are late manifestations of pituitary failure, and hence disease is usually advanced at this stage. • Retro-orbital pain and headache (0 – 40%), most likely caused by meningeal irritation, or rarely, by increased intracranial pressure from apoplexy of sellar metastasis.16 • Ophthalmoplegia (15– 43%), due to extension into the cavernous sinus of a very large tumor or in rare instances, pituitary apoplexy.17 The most commonly involved cranial nerves are III and IV. The combination leads to various degrees of ophthalmoplegia. • Visual field deficits (7–33%), the most common being bitemporal hemianopsia from invasion of the optic chiasm. Other less common manifestations include altered mental status, seizures, and eating disorders.5–8,12–17 These findings are not specific for metastatic cancer. Primary pituitary tumors such as pituitary adenomas may present similarly. However, the development of new-onset diabetes insipidus in any patient with known metastatic cancer should prompt a physician to look for PMs. Imaging Currently, it is not possible to differentiate PM from pituitary adenoma solely on the basis of radiographic appearance. However, certain characteristics have been described more commonly in PM, including (1) a computed tomographic (CT) scan revealing a sellar mass causing erosion of the sellar floor without causing sellar enlargement; (2) magnetic resonance imaging (MRI) findings of a dumbbell-shaped sellar mass with a clear margin at the diaphragm level, best seen on a sagittal image,17,18 and loss of-high intensity signals of the posterior pituitary in T1 weighed images; (3) angiography (if done), typically revealing significant tumor staining reflecting high vascularity.19 None of these radiologic findings are sufficiently specific for PM; similar patterns may be present in primary pituitary tumors. Diagnosis The diagnosis is based on histology because of the paucity of specific clinical and radiologic findings. A transsphenoidal biopsy for diagnosis has been considered very infrequently because of the mimicry between metastatic tumors and pituitary adenomas. The latter require a complete excision. Hence, the current means of
154
Gastrointestinal Cancer Research
establishing diagnosis is by transsphenoidal excision of the tumor.17–20 Not uncommonly, the diagnosis is established only at autopsy. Prognosis and Management The prognosis is uniformly poor, with mean survival between 6 and 22 months.4,9–12 Therefore, management should be directed at treatment of the primary cancer; local treatment with surgery, radiation, or both; and palliation of symptoms. Surgery and radiation therapy have typically been used, whereas the role of chemotherapy is unclear, but it may help if the primary tumor is sensitive to treatment. The role of surgery (ie, transsphenoidal resection) may be limited to palliation of significant symptoms, such as vision loss and ophthalmoplegia, and may be avoided otherwise, unless it is needed to establish the diagnosis in unclear cases. Radiation treatment is an option for most of the patients who present with endocrinologic disturbances. Recently gamma knife stereotactic surgery has emerged as a potential therapeutic option.21 It has been a matter of debate whether whole-brain irradiation or limited-field radiation is optimal for these patients,4 because of the lack of sufficient data from the rarity of the disease itself. However, both surgery and radiation have been shown to improve the quality of life without significantly improving survival.12 It should also be noted that there is a significant role for endocrine treatments such as supplemental corticosteroids for patients with hypocortisolism, thyroid hormones for hypothyroidism, and desmopressin or carbamazepine for central diabetes insipidus. Since the clinical features of the former two conditions resemble depression, which is very common in this population, the diagnosis may be delayed unless it is actively sought. Similarly, the oral intake of these patients is typically poor, leading to dehydration and hypernatremia, which may disguise the underlying cause of central diabetes insipidus. Hence, consideration of pituitary involvement in the differential diagnoses would be prudent in any patient with disseminated cancer presenting with these symptoms.
CONCLUSIONS Rarely, colon cancer recurs in uncommon sites such as the pituitary gland. PM presents in the setting of disseminated metastatic disease and remains an uncommon clinical condition. The representative patient population for this diagnosis is known to have metastatic cancer and presents with posterior or anterior pituitary failure. The incidence of brain metastasis in colon cancer is expected to increase because of the increased survival of patients with this malignancy.2 If clinical suspicion is high for metastasis, benefits from aggressive measures must be weighed against the risks of compromising quality of life, given the absence of documented survival benefit with any therapeutic measures. Palliative chemotherapy and targeted therapy for colon cancer have been effective in controlling systemic disease and prolonging overall survival of metastatic colon cancer. Both surgery and radiation treatments are palliative. Management of coexistent endocrine abnormalities is important and has a significant role in maintaining the quality of life in these terminally ill patients. A multidisciplinary team approach is also important in the management of this rare complication of colon cancer. Volume 6 • Issue 5– 6
Case Reports in GI Oncology REFERENCES 1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 62:10 –29, 2012 2. Mongan JP, Fadul CE, Cole BF, et al: Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. Clin Colorectal Cancer 8:100 –105, 2009 3. Max MB, Deck MD, Rottenberg DA: Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 31: 998 –1002, 1981 4. Fassett DR, Couldwell WT: Metastases to the pituitary gland. Neurosurg Focus 16:998 –E8, 2004 5. Tomita H, Urui S, Kokunai T, et al: A case of metastatic tumor of the pituitary gland presenting as a subarachnoid hemorrhage (in Japanese). No Shinkei Geka 28:1117–20, 2000 6. Neroni M, Artico M, Pastore FS, et al: Diaphragma sellae metastasis from colon carcinoma mimicking a meningioma: a case report. Neurochirurgie 45:160 –163, 1999 7. Nimura Taro OT, Goto Hideki, et al: Magnetic Resonance Imaging Characteristics of Pituitary Metastasis from Colon Cancer Associated with Diabetes Insipidus: A Case Report. Progress in Computed Imaging 1998 8. Stalldecker G, Molina HA, Antelo N, et al: Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis (in Spanish). Medicina (B Aires) 54:248 –52, 1994 9. Benjamin L: Ein Krebsfall. Virchows Archiv Pathol Anat 12:248 –561, 1857 10. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 3:74 – 85, 1950 11. Teears RJ, Silverman EM: Clinicopathologic review of 88 cases of carcinoma metastatic to the pituitary gland. Cancer 36:216 –20, 1975 12. Morita A, Meyer FB, Laws ER, Jr: Symptomatic pituitary metastases. J Neurosurg 89:69 –73, 1998 13. Houck WA, Olson KB, Horton J: Clinical features of tumor metastasis to the pituitary. Cancer 26:656 –9, 1970
September–December 2013
14. Nishio S, Tsukamoto H, Fukui M, et al: Hypophyseal metastatic hypernephroma mimicking a pituitary adenoma: case report. Neurosurg Rev 15: 319 –22 15. Cox EV 3rd: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:49 –50, 1979 16. Chhiber SS, Bhat AR, Khan SH, et al: Apoplexy in sellar metastasis: a case report and review of literature. Turk Neurosurg 21:230 –234, 2011 17. Komninos J, Vlassopoulou V, Protopapa D, et al: Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 89:574 –580, 2004 18. Mao JF, Zhang JL, Nie M, et al: Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: clinical presentations, diagnosis, and management. J Postgrad Med 57:302– 6, 2011 19. Yokoyama T, Yoshino A, Katayama Y, et al: Metastatic pituitary tumor from renal cell carcinoma treated by fractionated stereotactic radiotherapy: case report. Neurol Med Chir (Tokyo) 44:47–52, 2004 20. McCormick PC, Post KD, Kandji AD, et al: Metastatic carcinoma to the pituitary gland. Br J Neurosurg 3:71–79, 1989 21. Mori Y, Kobayashi T, Shibamoto Y. Stereotactic radiosurgery for metastatic tumors in the pituitary gland and the cavernous sinus. J Neurosurg 105(Suppl):37– 42, 2006
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Danny Issa, MD, Department of Internal Medicine, Fairview Hospital Cleveland Clinic, 18101 Lorain Road, Cleveland, OH 44111. Phone: (216) 476-7029 or (216)-476-7078; Fax: (216) 476-2944; E-mail: [email protected]
www.myGCRonline.org
155
