Clinical features of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis: a new aspect of paraneoplastic autoimmune condition.

The pathogenesis of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis postimmune checkpoint inhibitor therapy. All 9 patients exhibited extremely low growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels; 2 had a slightly atrophic pituitary gland; 4 had thymoma, and 5 had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in 5 cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis.

Survey of glucocorticoid dose escalation in patients with adrenal insufficiency during the peri-COVID-19 vaccination period.

There is uncertainty regarding the need for COVID-19 peri-vaccination glucocorticoid coverage in patients with adrenal insufficiency. In this survey conducted in a single tertiary medical institution, 167 consecutive outpatients taking physiological glucocorticoids because of adrenal insufficiency were included. The patients declared if they developed an adrenal crisis after vaccination, and the amount and duration of an increase in their glucocorticoid dosage, if any. None of the patients without preventive glucocorticoid increase suffered an adrenal crisis after COVID-19 vaccination. Only 8.3% (14 cases) and 27.5% (46 cases) of the patients needed to escalate the dose of glucocorticoids when systemic symptoms appeared after the first and second injections, respectively. Glucocorticoids were increased in patients <60 years of age more than in patients ≥60 years of age at the time of both the first (p = 0.026) and second injections (p = 0.005). Sex and the causes of adrenal insufficiency were not associated with the frequency of the patients who needed glucocorticoid dose escalation. In the cases with increased glucocorticoids, the median dosage for escalation was 10 mg (hydrocortisone equivalent). In conclusion, even without prophylactic glucocorticoid administration, adrenal crisis did not occur during the peri-COVID-19 vaccination period. The dose escalation of steroid was more frequent in younger patients following the second vaccination. Careful monitoring of adverse effects and the appropriate management of glucocorticoids when necessary are essential following COVID-19 vaccinations.

Case report: Late middle-aged features of FAM111A variant, Kenny-Caffey syndrome type 2-suggestive symptoms during a long follow-up.

Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare skeletal disorder involving hypoparathyroidism and short stature. It has an autosomal dominant pattern of inheritance and is caused by variants in the FAM111 trypsin-like peptidase A (FAM111A) gene. This disease is often difficult to diagnose due to a wide range of more common diseases manifesting hypoparathyroidism and short stature. Herein, we present the case of a 56-year-old female patient with idiopathic hypoparathyroidism and a short stature. The patient was treated for these conditions during childhood. Upon re-evaluating the etiology of KCS2, we suspected that the patient had the disorder because of clinical manifestations, such as cortical thickening and medullary stenosis of the bones, and lack of intellectual abnormalities. Genetic testing identified a heterozygous missense variant in the FAM111A gene (p.R569H). Interestingly, the patient also had bilateral sensorineural hearing loss and vestibular dysfunction, which have been rarely described in previous reports of pediatric cases. In KCS2, inner ear dysfunction due to Eustachian tube dysfunction may progress in middle age or later. However, this disease is now being reported in younger patients. Nevertheless, our case may be instructive of how such cases emerge chronically after middle age. Herein, we also provide a literature review of KCS2.

Evaluation of GENECUBE Mycoplasma for the detection of macrolide-resistant Mycoplasma pneumoniae.

Introduction. Resistance against macrolide antibiotics in Mycoplasma pneumoniae is becoming non-negligible in terms of both appropriate therapy and diagnostic stewardship. Molecular methods have attractive features for the identification of Mycoplasma pneumoniae as well as its resistance-associated mutations of 23S ribosomal RNA (rRNA).Hypothesis/Gap Statement. The automated molecular diagnostic sytem can identify macrolide-resistant M. pneumoniae.Aim. To assess the performance of an automated molecular diagnostic system, GENECUBE Mycoplasma, in the detection of macrolide resistance-associated mutations.Methodology. To evaluate whether the system can distinguish mutant from wild-type 23S rRNA, synthetic oligonucleotides mimicking known mutations (high-level macrolide resistance, mutation in positions 2063 and 2064; low-level macrolide resistance, mutation in position 2067) were assayed. To evaluate clinical oropharyngeal samples, purified nucleic acids were obtained from M. pneumoniae-positive samples by using the GENECUBE system from nine hospitals. After confirmation by re-evaluation of M. pneumoniae positivity, Sanger-based sequencing of 23S rRNA and mutant typing using GENECUBE Mycoplasma were performed.Results. The system reproducibly identified all synthetic oligonucleotides associated with high-level macrolide resistance. Detection errors were only observed for A2067G (in 2 of the 10 measurements). The point mutation in 23S rRNA was detected in 67 (26.9 %) of 249 confirmed M. pneumoniae-positive clinical samples. The mutations at positions 2063, 2064 and 2617 were observed in 65 (97.0 %), 2 (3.0 %) and 0 (0.0 %) of the 67 samples, respectively. The mutations at positions 2063 and 2064 were A2063G and A2064G, respectively. The results from mutant typing using GENECUBE Mycoplasma were in full agreement with the results from sequence-based typing.Conclusion. GENECUBE Mycoplasma is a reliable test for the identification of clinically significant macrolide-resistant M. pneumoniae.

Does the extension of the type of hysterectomy contribute to the local control of endometrial cancer?

OBJECTIVE: To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. METHODS: This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I-III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. RESULTS: Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506-16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701-6.547, p < 0.001) and III (HR 2.445, 95% CI 1.280-4.668, p = 0.007), vs stage I and histological type 2 (HR 1.610, 95% CI 0.938-2.762, p = 0.001). CONCLUSIONS: For endometrial cancer patients requiring surgery, the selection of a more extensive type of hysterectomy did not reduce the rate of local recurrence. Therefore, there is little significance in performing mRH in such cases.

Analysis of uterine corporeal mesenchymal tumors occurring after menopause.

OBJECTIVE: Because it is difficult to diagnose accurately whether uterine corporeal mesenchymal tumors are benign or malignant before surgery, an understanding of the characteristics of patients with uterine sarcomas occurring in the postmenopausal period is required. METHODS: We retrospectively reviewed the cases of women who underwent surgery for uterine mesenchymal tumors at our hospital. RESULTS: Among 487 operated cases, 447 tumors occurred in the premenopausal period and 40 occurred in the postmenopausal period. Uterine sarcomas were observed in 5 cases (1.1%) during the premenopausal period and in 11 cases (28%) during the postmenopausal period. Among the postmenopausal patients, age, age at menopause, body mass index (BMI), tumor size, incidence of abnormal vaginal bleeding, serum tumor marker levels (cancer antigen 125, carbohydrate antigen 19-9, and carcinoembryonic antigen), and serum lactate dehydrogenase values were not significantly different between patients with benign tumors and those with malignant tumors. On the other hand, the incidence to have abnormal signal on MRI was significantly higher in patients with malignant tumors than in patients with benign tumors. CONCLUSION: In our hospital, the incidence of malignant tumors in women with uterine corporeal mesenchymal tumors was much higher in postmenopausal patients than in premenopausal patients. Because it is generally not easy to diagnose uterine sarcomas before surgery, surgery should be positively considered when uterine sarcomas cannot be ruled out for patients in the postmenopausal period.

Significance of postmenopausal uterine leiomyomas: Focus on variants.

AIM: To investigate the differences in leiomyoma pathophysiology by patient age at the time of surgery and the possible significance of postmenopausal uterine leiomyomas, particularly variants. METHODS: We retrospectively reviewed data from 471 patients who underwent surgery for uterine leiomyomas and evaluated their clinical data. RESULTS: Overall, 441 (93.4%) women were premenopausal and 30 (6.4%) were postmenopausal. There were no differences in the frequency of the coexistence of ovarian steroid-dependent diseases among age groups. Common histopathological features were observed in most cases despite menopausal status; however, the incidence of variants among postmenopausal patients was high compared to that among premenopausal women (23.3% [7/30] vs 3.2% [14/441], respectively). Among the variant leiomyomas in postmenopausal patients, lipoleiomyomas comprised six. CONCLUSION: Although progesterone is known to play a vital role in promoting leiomyoma growth, it reportedly performs dual actions and does not always stimulate leiomyoma growth. Our study may support the idea that the dual action of progesterone is the primary reason for the surgical treatment required for uterine leiomyomas in the postmenopausal period. We also found that lipoleiomyoma might be the most common uterine leiomyoma variant requiring surgical treatment among postmenopausal women. Thus, we must consider the diagnosis of uterine lipoleiomyoma in postmenopausal women with uterine leiomyomas.

A case of uterine carcinosarcoma which was strongly suspected to have metastases to the psoas and gluteus muscles.

Metastasis to the skeletal muscles is uncommon. We report a case which was strongly suspected to have psoas and gluteus muscle metastases from uterine carcinosarcoma. A 68-year-old woman (gravida, 2; para, 0) underwent retroperitoneal endoscopic paraaortic lymphadenectomy, laparoscopic modified radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy for uterine carcinosarcoma, suspected to be stage IB. Metastasis to one right pelvic lymph node was observed. Ascites fluid cytology was negative. Postoperative pathological examination revealed stage IIIC1 (pT1bN1M0) disease. Five cycles of chemotherapy with paclitaxel + carboplatin were performed. 10 months after chemotherapy, serum cancer antigen-125 level was elevated. Computed tomography (CT) revealed a 3-cm tumor of the left psoas muscle and magnetic resonance imaging revealed a tumor of the left gluteus maximus muscle. These lesions showed fluorodeoxyglucose uptake in positron emission tomography-CT. Because we considered the tumors were metastases of uterine carcinosarcoma, we recommended her chemotherapy. However, after one cycle of chemotherapy, the patient underwent immunotherapy elsewhere with immune checkpoint inhibitors. 5 months after the recurrence, she was alive.

Hyperthyroidism due to struma ovarii: Diagnostic pitfalls and preventing thyroid storm.

We report struma ovarii in a case that had hyperthyroidism and was treated with laparoscopic tumor resection. A 40-year-old Japanese woman presented with tachycardia, finger tremor, and weight loss. Although blood examination showed hyperthyroidism, test results for thyroid stimulating hormone receptor antibody and thyroid stimulating antibody were negative, and thyroid scintigraphy showed no abnormal findings. Because she was diagnosed with an ovarian tumor, and whole-body scintigraphy showed that iodine uptake was detected in the pelvic space, we diagnosed her with an ovarian tumor, which caused excessive thyroid hormone secretion. After controlling the thyroid hormone level, we resected the ovarian tumor laparoscopically. The thyroid hormone level was within the normal range postoperatively without any medications. Based on our experience, physicians need to remember that ovarian tumors can cause hyperthyroidism. Controlling the thyroid hormone level preoperatively by using antithyroid drugs and performing minimally invasive laparoscopic surgery is considered useful for preventing thyroid storm.

Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components.

A 61-year-old Japanese woman was diagnosed with FIGO Stage IB endometrioid cancer (EC) combined with large cell neuroendocrine carcinoma (LCNEC). Metastasis to the lymph nodes in the right bronchopulmonary area, mediastinum and brain were also identified. The patient eventually developed pleuritis and pericarditis carcinomatosa, and died of cancer at 51 months after surgery. Because gene aberrations in uterine neuroendocrine carcinoma are still not well understood, we examined alterations in the mutational hotspots of 50 selected cancer-associated genes. The EC and LCNEC components shared identical alterations in PTEN, PIK3CA and FGFR3. Both the EC and LCNEC components had heterozygous SBSs on CTNNB1 but at different codons (G34R in EC, and T41A in LCNEC). The altered gene signature raised a possibility that the EC and LCNEC components were derived from a common precursor lesion. The LCNEC independently obtained a significant CTNNB1 mutation and the lymph node metastasis originated from this component. Because the LCNEC component seemed to bring about the aggressive course of the disease and defined the patient outcome, further investigations are needed to elucidate the mechanism of NE carcinoma development in the endometrium.