Carney syndrome in a patient previously considered to have Peutz-Jeghers syndrome
Authors: Justin D. Richey, Joshua R. Bradish, Shanon R. Lacy, Simon Warren
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: We report a case of Carney syndrome in an 18-year-old male patient who presented with a previous diagnosis of Peutz-Jeghers syndrome and a rapidly growing asymptomatic tumor of his right upper lip, present for the past 7 months. Since age 6 years, this patient has had multiple lentigines of his face and oral mucosa. Approximately 3 years before coming to our attention, he had bilaterally enlarged testicles and a right orchiectomy that revealed a large cell calcifying Sertoli cell tumor. A review of systems also revealed occasional bloody stools. At that time, the patient was incorrectly diagnosed with Peutz-Jeghers syndrome and gastrointestinal surveillance was initiated. Endoscopy revealed a single 5-mm sessile polyp on the duodenal bulb that was not biopsied. Colonoscopy was unremarkable. Additional studies, including thyroid and endoscopic ultrasound as well as genetic evaluation, were not performed. His family history was negative for mucocutaneous lesions, gastrointestinal polyps, or myxomas. When the patient presented at this institution, physical examination revealed a single, 7-cm, firm, nontender tumor involving the right upper lip with 2 flesh-colored, 0.5-cm papules overlying the surface. There were also multiple dark pigmented macules involving the face, lips, and oral mucosa. The tumor was biopsied and revealed a myxoid spindle cell proliferation with mild to moderate cellularity. The patient underwent reconstructive surgery for complete excision. Gross examination revealed a 7- × 3.8- × 3.3-cm tumor. Microscopic examination demonstrated a hypercellular spindle cell proliferation with rich vascular network of thin-walled vessels, numerous neutrophils, and myxoid background that infiltrated adjacent connective tissue (Fig 1). Immunohistochemical staining was positive for vimentin and CD34 and negative for S100, AE1/AE3, factor XIIIa, and actin. The lesion was called a superficial angiomyxoma, the patient was correctly diagnosed with Carney syndrome, and proper follow-up was initiated. This case highlights the importance of following strict diagnostic criteria as well as understanding the pathology behind the diagnostic criteria of Peutz-Jeghers and Carney syndrome (Table I). The incorrect diagnosis of Peutz-Jeghers was made prematurely because diagnostic criteria had not yet been met.1Amos C.I. Frazier M.L. Wei C. McGarrity T.J. Peutz-Jeghers Syndrome.in: Pagon R.A. Bird T.D. Dolan C.R. Stephens K. Adam M.P. GeneReviews. University of Washington, Seattle, Seattle, WA1993Google Scholar This prompted inappropriate follow-up (gastrointestinal surveillance) looking for intestinal polyps. Peutz-Jeghers associated polyps are a disorganized growth of normal tissue (hamartomatous) with a smooth muscle core that is unique to Peutz-Jeghers polyps and not seen in patients with Carney syndrome.2Burkart A.L. Sheridan T. Lewin M. Fenton H. Ali N.J. Montgomery E. Do sporadic Peutz-Jeghers polyps exist? Experience of a large teaching hospital.Am J Surg Pathol. 2007; 31: 1209-1214Crossref PubMed Scopus (45) Google Scholar Regardless of whether these polyps carry malignant potential, obtaining a biopsy helps fulfill diagnostic criteria when the diagnosis is still in question. Both syndromes share mucocutaneous lentigines as a feature but only Carney syndrome is associated with superficial angiomyxomas.3Stratakis C.A. Horvath A. Carney Complex.in: Pagon R.A. Bird T.D. Dolan C.R. Stephens K. Adam M.P. GeneReviews. University of Washington, Seattle, Seattle, WA1993Google Scholar It is important to recognize when these occur, because there is a higher risk of cardiac myxomas that can obstruct blood flow and cause heart failure.4Wang L.W. Granger E.K. Obstructive right atrial myxoma in association with Carney complex.Heart Lung Circ. 2013; 22: 450-451Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Physicians should rule out Carney syndrome and Peutz-Jeghers syndrome when a patient presents with features common to both. Finding one additional feature unique to either improves diagnostic certainty and guides the physician toward a proper follow-up and surveillance strategy. Recommended follow-up can help detect precursor lesions and other complications before they become life threatening.5Beggs A.D. Latchford A.R. Vasen H.F. Moslein G. Alonso A. Aretz S. et al.Peutz-Jeghers syndrome: a systematic review and recommendations for management.Gut. 2010; 59: 975-986Crossref PubMed Scopus (519) Google ScholarTable IPeutz-Jegher and Carney syndrome comparison chart. Similar features in boldPeutz-JeghersCarneyDiagnostic criteria2 of 3 criteria:•Characteristic mucocutaneous pigmentation•Histologically confirmed PJS-type polyps•Family history of characteristic polyps or mucocutaneous pigmentation1 criterion from clinical presentation and at least 1 additional criterion from either clinical presentation or tumors. (Seek 1 additional criterion if both criteria found are not unique to Carney.)GeneticsAutosomal dominant, chr. 19p and 19q loci. Genes: STK11 (LKB1)Autosomal dominant, chr. 2p16 and 17q22–24 loci. Genes: PRKARIA and othersClinical presentation•Mucocutaneous, pigmented spots of lips and buccal mucosa•Gynecomastia and growth acceleration•Mucocutaneous pigmented spots of face, lips, eyelids, conjunctiva, and oral mucosa•Gynecomastia, growth acceleration, acromegalyTumors•Sertoli cell tumors•Sex cord tumors with annular tubules•Various cancerous and precancerous lesions from:○Breast○Thyroid○Small intestine○Colon○Stomach○Pancreas○Esophagus○Ovary○Lung○Uterus○Uterine cervix•Large cell calcifying Sertoli cell tumor•Breast myxomatosis•Breast ductal adenomas•Thyroid carcinoma•Myxomas: cutaneous, mucosal, and cardiac•Growth hormone producing adenoma•Psammomatous melanotic schwannomas•Blue nevus, epithelioid blue nevus•OsteochondromyxomaEvaluation following initial diagnosis•Genetics consultation•Men: testicular ultrasound•Women: gynecologic and breast examination•Upper endoscopy plus small bowel examination (MR or CT enterography, wireless capsule endoscopy)•Colonoscopy•Genetics consultation•Men: testicular ultrasound•Women: transabdominal ultrasound•Imaging or biochemical screening for endocrine tumors•Thyroid ultrasoundSurveillance•Annual history, physical, and routine blood work•Testicular exam (ultrasound if symptomatic)•Colonoscopy and upper GI endoscopy•Annual history, physical, and routine blood work•Testicular exam (ultrasound if symptomatic)•Monitor linear growth rate and pubertal staging.•Annual or biannual echocardiograms•Further evaluation as indicated:○Diurnal cortisol levels○Dexamethasone stimulation test○3-hour oral glucose tolerance test○90-minute thyroid releasing hormone○MRI of the brain, spine, chest, abdomen, retroperitoneum, pelvisBold items indicate where Peutz-Jeghers and Carney syndrome are similar. When making a specific diagnosis, physicians should make sure they are using more than just the ones in bold to distinguish between the two syndromes. Open table in a new tab Bold items indicate where Peutz-Jeghers and Carney syndrome are similar. When making a specific diagnosis, physicians should make sure they are using more than just the ones in bold to distinguish between the two syndromes.