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00019616-200807000-00002ReportThe EndocrinologistThe Endocrinologist© 2008 Lippincott Williams & Wilkins, Inc.18July 2008 p 161-162Cushing Syndrome Secondary to Ectopic ACTH Secretion by Dedifferentiated Acinic Cell Carcinoma of the Parotid GlandCase ReportButt, Muhammad Imran MRCP; Rose, D Simon C. FRCPATH; Robinson, Anthony M. FRCPFrom the Royal United Hospital, Bath, UK.Reprints: Dr Muhammad Imran Butt, MRCP, Specialist Registrar, Endocrinology, Royal United Hospital, Bath, BA1 3NG, UK. E-mail: [email protected] 60-year-old man presented with an acute confusional state 2 months after parotidectomy for dedifferentiated adenocarcinoma of the parotid gland with nodal metastasis. Investigation indicated ectopic adrenocorticotropic hormone (ACTH) production from metastatic parotid carcinoma resulting in Cushing syndrome. Parotid gland adenocarcinoma is an extremely rare source of ectopic ACTH production with only 2 cases previously reported in the literature, both of which were conventional acinic cell carcinoma. This is a first case report of a dedifferentiated acinic cell carcinoma causing ectopic ACTH syndrome.Salivary gland tumors are rare, accounting for 2 to 3 cases per 100,000 per year. The parotid is the commonest site. Swelling of the gland is the usual presenting symptom. Treatment of salivary gland carcinoma includes surgery, radiotherapy, and chemotherapy. Prognosis depends largely on the initial stage of the tumor.The literature contains 2 case reports of ectopic adrenocorticotropic hormone (ACTH) secretion from metastatic acinic cell carcinoma (ACC) of the parotid.1,2 Usually ACC is a well-differentiated tumor, but rarely it presents with a dedifferentiated subtype. We report the first case of dedifferentiated ACC of the parotid gland tumor with ectopic ACTH secretion.CASE REPORTA 60-year-old man was referred to the ENT department with a 3-week history of left-sided facial swelling. Examination revealed a firm mass involving the left parotid gland. Fine needle aspiration cytology confirmed malignancy and raised the suspicion of acinic cell carcinoma (ACC). Elective exploration was carried out to remove the tumor but it was locally extensive and the morphology and size of regional lymph glands was consistent with metastasis. Left parotidectomy was performed and radical neck dissection planned after the formal staging. Staging MRI scan of the head and neck was consistent with metastatic involvement of the ipsilateral lymph glands (Fig. 1). CT chest was normal. Parotidectomy and radical neck dissection was performed. Most of the parotid tumor was ACC of usual type with a microcystic architecture and focally a prominent lymphocytic infiltrate (Fig. 2). However, both in areas of the primary parotid tumor, and predominating in the metastases, the tumor cells showed more pleomorphism with anisonucleosis, frequent mitotic figures and swathes of necrosis (Fig. 3). These features are characteristic of the dedifferentiated variant of ACC and are associated with high tumor stage and poor prognosis.3 The clinical stage of the malignancy was IVa (T3, N2, M0), and pathologic stage was pT3 pN2b pMX. He made an uneventful recovery and was discharged with radiotherapy planned as an outpatient.JOURNAL/endst/04.03/00019616-200807000-00002/figure1-2/v/2021-02-17T201851Z/r/image-tiff Staging MR head and neck before radical neck dissection.JOURNAL/endst/04.03/00019616-200807000-00002/figure2-2/v/2021-02-17T201851Z/r/image-tiff Conventional acinic cell carcinoma with microcystic growth pattern, focal fine basophilic cytoplasmic granularity and a lymphocytic infiltrate.JOURNAL/endst/04.03/00019616-200807000-00002/figure3-2/v/2021-02-17T201851Z/r/image-tiff Dedifferentiated area with more pleomorphism, mitoses and necrosis.He was admitted via the emergency department 2 months later with a 1-week history of acute confusional state, paranoid behavior, and hallucinations. There were no previous mental health problems, and he was not on any regular medications. The systemic examination was unremarkable except for the presence of bilateral leg edema. Initial screening investigations were all normal except for hypokalemia (K+ 2.4 mmol/L). CT brain, lumbar puncture, and electroencephalogram did not reveal any cause for his confusion. In view of hypokalemic metabolic alkalosis (venous bicarbonate 34 mmol/L), hypercortisolism was suspected. This was supported by morning serum cortisol of 1575 nmol/L (range 171–536 between 7:00 am–10:00 am), 24-hour urinary free cortisol 15374 nmol/d (<280) and ACTH levels 106 ng/L (normal <40 ng/L). Serum cortisol levels failed to suppress with low and high dose dexamethasone suppression tests. Urinary 5-HIAA were in normal range. MRI scan of the pituitary gland was normal. CT chest showed mediastinal and hilar lymphadenopathy consistent with metastatic disease (Fig. 4). Abdominal CT revealed bilateral generalized enlargement of the adrenal glands suggestive of hyperstimulation. He is being treated with metyrapone, hydrocortisone, and palliative chemotherapy with gemcitabine and docetaxel. This has resulted in clinical and biochemical improvement after 2 cycles of chemotherapy. The recent thoracic CT confirmed no further spread of the tumor and shrinkage of the existing lymph nodes.JOURNAL/endst/04.03/00019616-200807000-00002/figure4-2/v/2021-02-17T201851Z/r/image-tiff CT chest showing lymph node metastasis.The diagnosis of ectopic ACTH secretion causing Cushing syndrome was made. Metastatic carcinoma of the parotid gland represents the obvious source. Although the parotid gland tumor did not stain for ACTH, it is commonly reported occurrence in high secreting tumors.4 While 2 previous cases of metastatic parotid ACC with ACTH secretion have been reported, in neither is the primary tumor reported as being of the rarer dedifferentiated subtype, though the description of the metastatic disease in Cox's report2 suggests subsequent dedifferentiation of the tumor in their case.SUMMARY POINTSParotid carcinoma is a rare but a recognized source of ectopic ACTH secretion.REFERENCES1. Jamieson L, Taylor SM, Smith A, et al. Metastatic acinic cell carcinoma of the parotid gland with ectopic ACTH syndrome. Otolaryngol Head Neck Surg. 2007;136:149–150.[Context Link][Full Text][CrossRef][Medline Link]2. Cox ML, Gourley DR, Kitabachi AE. Acinic cell adenocarcinoma of the parotid with ectopic production of adrenocorticotropic hormone. Am J Med. 1970;49:529–533.[Context Link][CrossRef][Medline Link]3. Henley JD, Geary WA, Jackson CL, et al. Dedifferentiated acinic cell carcinoma of the parotid gland: a distinct rarely described entity. Hum Pathol. 1997;28:869–873.[Context Link][CrossRef][Medline Link]4. Grossman AB, Kelly P, Rockall A, et al. Cushing's syndrome caused by an occult source: difficulties in diagnosis and management. Nat Clin Pract Endocrinol Metab. 2006;2:642–647.[Context Link]ectopic ACTH secretion; Cushing syndrome; parotid adenocarcinoma00019616-200807000-0000200002090_2007_136_149_jamieson_metastatic_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e237_citationRF_FLOATING))|11065404||ovftdb|SL00002090200713614911065404citation_FROM_JRF_ID_d67e237_citationRF_FLOATING[Full Text]00006372-200701000-0003700019616-200807000-0000200002090_2007_136_149_jamieson_metastatic_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e237_citationRF_FLOATING))|11065213||ovftdb|SL00002090200713614911065213citation_FROM_JRF_ID_d67e237_citationRF_FLOATING[CrossRef]10.1016%2Fj.otohns.2006.04.00900019616-200807000-0000200002090_2007_136_149_jamieson_metastatic_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e237_citationRF_FLOATING))|11065405||ovftdb|SL00002090200713614911065405citation_FROM_JRF_ID_d67e237_citationRF_FLOATING[Medline Link]1721035700019616-200807000-0000200000439_1970_49_529_cox_adrenocorticotropic_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e274_citationRF_FLOATING))|11065213||ovftdb|SL0000043919704952911065213citation_FROM_JRF_ID_d67e274_citationRF_FLOATING[CrossRef]10.1016%2FS0002-9343%2870%2980047-X00019616-200807000-0000200000439_1970_49_529_cox_adrenocorticotropic_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e274_citationRF_FLOATING))|11065405||ovftdb|SL0000043919704952911065405citation_FROM_JRF_ID_d67e274_citationRF_FLOATING[Medline Link]432053100019616-200807000-0000200004185_1997_28_869_henley_dedifferentiated_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e309_citationRF_FLOATING))|11065213||ovftdb|SL0000418519972886911065213citation_FROM_JRF_ID_d67e309_citationRF_FLOATING[CrossRef]10.1016%2FS0046-8177%2897%2990164-700019616-200807000-0000200004185_1997_28_869_henley_dedifferentiated_|00019616-200807000-00002#xpointer(id(citation_FROM_JRF_ID_d67e309_citationRF_FLOATING))|11065405||ovftdb|SL0000418519972886911065405citation_FROM_JRF_ID_d67e309_citationRF_FLOATING[Medline Link]9224759 Staging MR head and neck before radical neck dissection. Conventional acinic cell carcinoma with microcystic growth pattern, focal fine basophilic cytoplasmic granularity and a lymphocytic infiltrate. Dedifferentiated area with more pleomorphism, mitoses and necrosis. CT chest showing lymph node metastasis.Cushing Syndrome Secondary to Ectopic ACTH Secretion by Dedifferentiated Acinic Cell Carcinoma of the Parotid GlandButt Muhammad Imran MRCP; Rose, D Simon C. FRCPATH; Robinson, Anthony M. FRCPCase ReportCase Report418p 161-162