Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?

AIMS: The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk. METHODS AND RESULTS: In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and "adenomatous nodules" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression. CONCLUSIONS: Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.

Heterotopic Nodules in the Placenta, an Immunohistochemical Re-evaluation of the Diagnosis of Adrenocortical Heterotopia.

BACKGROUND: Rare nodules of heterotopic adrenocortical and hepatic tissue are reported in the placenta. A mechanism for adrenocortical tissue in the placenta has been perplexing, while hepatic tissue is generally considered related to yolk sac primordia. The clear cell morphology of these nodules is similar to the adrenal cortex of the adult; however, the fetal adrenal gland does not usually display clear cells. METHODS: We stained 9 placental nodules, histologically identical to "adrenocortical" heterotopia of the placenta, to determine whether adrenocortical differentiation could be confirmed. These cases include 3 archival cases initially diagnosed as "adrenocortical" heterotopia. RESULTS: Immunohistochemical staining with steroid factor-1 (SF-1), HepPar-1, and Arginase-1 showed that these nodules of clear cells are actually hepatic (SF-1 negative, HepPar-1, and Arginase-1 positive). PAS staining suggests that glycogen accumulation is responsible for the clear cytoplasm. In contrast, a nodule of adrenocortical heterotopia near the testis and the adrenal gland from a 38-week-old neonatal autopsy case confirm SF-1 reactivity as expected. CONCLUSION: We propose that adrenocortical heterotopia in the placenta is a misnomer, and that these subchorionic nodules of clear cells demonstrate hepatic differentiation.

Diagnosis of Neonatal Herpes Simplex Infection from the Placenta.

Due to a high rate of fetal demise and premature birth in intrauterine HSV infection, the outcome in neonates is usually adverse. A female preterm infant with a gestational age of 25 1/7 weeks with expected early clinical course tested positive for neonatal herpes simplex virus (HSV) 2 after the neonatologist was informed of positive immunohistochemistry for the virus on the fifth day of life by the pathologist. Pathological examination of the placenta had revealed subacute necrotizing inflammation with stromal cell necrosis suggestive of intrauterine infection, possibly ascending due to prolonged rupture of membranes. To the best of our knowledge, this is the first case wherein placental pathology indicated exposure to HSV in utero before the infant presented with signs or symptoms of neonatal HSV resulting in a favorable outcome for the infant. Due to the variability of presentation of intrauterine HSV infection, pathological examination of the placenta in the first 2-5 days of life in premature infants can provide clues to the diagnosis of neonatal HSV which may significantly impact the outcome.

Endometrial Polyp of the Placental Fetal Membranes: Report of a Case.

Endometrial polyps embedded in the fetal membranes have only rarely been described. A review of the English literature showed only one abstract describing this occurrence and to the best of our knowledge, there have been no other publications of this entity. Herein we present a case of a 37-yr-old woman with a history prior abortion and complicated pregnancy (type 2 diabetes mellitus and preeclampsia) who delivered by cesarean section. Although the placenta did not show hypertensive vasculopathic changes or other pathologic findings, an endometrial polyp embedded within the fetal membranes was present. Recognition of this rarely reported entity is important in order to avoid confusion with a significant neoplastic process.

Anti-N-methyl-D-aspartate Encephalitis Concomitantly with Tall-cell Variant Papillary Thyroid Carcinoma.

Anti-N-methyl-D-aspartate (NMDA) encephalitis is an autoimmune-mediated process characterized by psychosis, seizures, dyskinetic movements, and autonomic instability. At least half of the reported cases are paraneoplastic, particularly associated with an ovarian teratoma. None have been reported to be associated with thyroid tumor. We present a case of anti-NMDA encephalitis concomitantly occurring in setting of papillary thyroid carcinoma in a woman who presented with headaches, myalgia and somnolence mimicking meningoencephalitis. A 29-year-old African female presented with fever, headache, myalgia, somnolence and behavioral changes. Initial evaluation was significant for lymphocytic pleocytosis with normal glucose and protein. She was started on broad spectrum empiric antibiotics. Despite antibiotics, she continued to have worsening encephalopathy, hallucinations, epileptic seizures, and multifocal dyskinesias involving the face and extremities with no electroencephalogram correlate. Extensive infectious workup was unremarkable. Whole-body CT with contrast and ovarian ultrasound were unremarkable for malignancy. Serum auto-antibodies to the NMDA receptor and thyroid peroxidase were detected. She was treated with high-dose intravenous steroids, plasmapheresis, intravenous immunoglobulin, and rituximab with no clinical or serological response. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed a hypermetabolic thyroid nodule. Fine needle aspiration of the nodule revealed papillary thyroid carcinoma. She underwent total thyroidectomy and pathology showed two foci of tall-cell variant papillary thyroid carcinoma. Serological and clinical response followed shortly after tumor resection. The NMDA receptor stain of the papillary thyroid carcinoma was nonreactive. We describe the coincidentally co-occurrence of NMDA encephalitis in a patient with papillary thyroid carcinoma. This case highlights the importance of presumed cases of non-paraneoplastic NMDA encephalitis, FDG-PET may help in detecting occult malignancies.

Virilizing ovarian Leydig cell tumor in a woman with subclinical Cushing syndrome.

OBJECTIVE: To report the case of a patient with a virilizing ovarian Leydig cell tumor and subclinical Cushing syndrome attributable to an adrenal adenoma. METHODS: Detailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed. RESULTS: A 49-year-old woman was referred for evaluation of a left adrenal mass (3.0 by 2.4 cm), which had been diagnosed by computed tomographic scan 4 years previously during a work-up for hirsutism. On examination, she had central obesity, facial hirsutism, and male pattern baldness. Work-up showed elevated total and free testosterone levels of 196 ng/dL (reference range, 20 to 70) and 24 pg/mL (1 to 9), respectively. Other results (and reference ranges) were as follows: dehydroepiandrosterone sulfate, 7.5 microg/dL (10 to 221); corticotropin, 12 pg/mL (5 to 50); morning cortisol, 1.4 microg/dL after a 1-mg overnight dexamethasone suppression test; and urine free cortisol, 48.8 microg/24 h (20 to 100). The testosterone level decreased by 14% after a 2-day low-dose dexamethasone suppression test. Findings on transvaginal ovarian ultrasonography and a computed tomographic scan of the pelvis were normal. A laparoscopic adrenalectomy revealed an adrenal adenoma. On the first day postoperatively, the cortisol level was less than 1.0 microg/dL; however, the testosterone level remained elevated. At 6 months postoperatively, a normal result of a cosyntropin stimulation test indicated recovery of the hypothalamic-pituitary-adrenal axis. Bilateral oophorectomy revealed a 1.3-cm right ovarian Leydig cell tumor. Postoperatively, the testosterone level declined to less than 20 ng/dL. CONCLUSION: To our knowledge, this is the first case report of a virilizing ovarian Leydig cell tumor in a patient with subclinical Cushing syndrome.