Acrochordons are polypoid, skin-colored lesions usually present at the site of skin folds. They are extremely rare in the preputial area of the penis and do not tend to grow. To the best of our knowledge, in English literature, this report presents the first case of an androgen receptor-positive penile acrochordon, which is located on the penis and showed rapid growth along with body development during puberty with no underlying causes such as acromegaly, diabetes, obesity, and trauma.

Androgen insensitivity syndrome (AIS) is a rare disorder with X-linked recessive inheritance in 46 XY patients. The clinical manifestations vary between patients, especially regarding external genitalia development. Herein, the case of AIS in a 13-year-old male, who was born with hypospadias and presented to the hospital with gynaecomastia that had developed from 8 years of age, is reported. No micropenis, cryptorchidism or bifid scrotum were found. Testis volume was 12 ml on both sides. His testosterone and luteinizing hormone levels were normal compared with sex- and age-adjusted reference range. His bone age was approximately 13 years according to Greulich-Pyle assessment. Sequence analysis of the androgen receptor (AR) gene revealed a mutation (c.2041A>G) in exon 4, a novel mutation site in the AR gene. Prediction analysis suggested this to be a disease-causing variant. A milder clinical presentation and normal hormone levels in cases of partial AIS might differ from the usually reported signs and symptoms. A diagnosis of AIS should not be ignored in teenage patients who present with gynaecomastia and hypospadias, but normal hormone levels.

Androgen insensitivity syndrome is a rare X-linked recessive condition in which patients present a female phenotype. After complete androgen insensitivity syndrome (CAIS) diagnosis, the timing of gonadectomy should be evaluated, considering the risks and benefits of this procedure. This paper reports an uncommon case of complete androgen insensitivity syndrome diagnosed belatedly in an adult patient. Surgical treatment was deemed necessary due to the elevated risk of gonadal malignancy.

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient\'s gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient\'s karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.

UNASSIGNED: With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR).
UNASSIGNED: We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals.
UNASSIGNED: The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group.
UNASSIGNED: AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.

Warthin\'s tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary duct carcinoma. He subsequently underwent left parotidectomy along with left level II-IV lymph node dissection. Histology revealed both in situ as well as invasive salivary duct carcinoma arising from Warthin tumor. Immunohistochemistry showed tumor cells positive for CK7, AR, and GATA3, while p63 highlighted the myoepithelial cell layer in the in situ component. Her2 was 2+ by immunohistochemistry. In addition, PD-L1 IHC revealed positive expression with a combined positive score of 20%.

UNASSIGNED: Several animal experiment studies have shown that insufficient testicular descent to the scrotum can be caused by persistence of cranial suspensory ligament (CSL). We report a case of right cryptorchidism in a male toddler surgically treated with an orchidopexy possibly associated with CSL persistence based on intraoperative and pathological findings. This case would be a precious source to further investigate the etiopathogenesis of cryptorchidism.
UNASSIGNED: The CSL anchors embryonic gonads to the dorsal abdominal wall during antenatal mammalian development. Although its persistence appears to cause cryptorchidism in animal models, it has never been proven in humans. A 1-year-old boy with right cryptorchidism underwent right orchidopexy. Intraoperatively, a band-like structure running from the right testis into the retroperitoneum and up to the right side of the liver was noticed and resected. The pathological findings of the specimen showed fibrous connective tissues, smooth muscles, and blood vessels but no tissues suggestive of a testis, a spermatic cord, an epididymis, or liver. Immunohistochemical analysis for an androgen receptor antibody did not detect any signal in the specimen. The right cryptorchidism in this case was possibly caused by CSL persistence, which is the first such human case, to our knowledge.

Uterine angioleiomyoma is benign tumor that composed of smooth muscle cells and thick-walled vessels. It is a very rare condition reported to present as lower abdominal mass, accompanied by dysmenorrhea and hypermenorrhea. However, its clinical presentation is not known.
We report the case of a 44-year-old Japanese woman who developed severe anemia with disseminated intravascular coagulation without obvious external bleeding. The patient had a huge abdominal mass of over 20 cm in size, which was thought to be a uterine tumor. She received daily blood transfusions and her condition improved rapidly after she underwent hysterectomy. Pathological examination of the tumor revealed spindle-shaped cells with little atypia and mitosis, and numerous large vessels with smooth muscle and thrombus in the vessels.
Uterine angioleiomyoma was identified as the cause of the coagulation abnormality. CCND2 and AR gene amplification was detected in the tumor. Uterine tumors that present with coagulopathy despite a clinical course suggestive of benign disease should undergo differential diagnosis for uterine angioleiomyoma.

UNASSIGNED: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature.
UNASSIGNED: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months.
UNASSIGNED: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.

Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several papers focusing on PROTACs against AR. This study explores the potential of a few in silico tools to extract drug design information from AR degradation data in the format often reported in the literature. After setting up a dataset of 92 PROTACs with consistent AR degradation values, we employed the Bemis-Murcko method for their classification. The resulting clusters were not informative in terms of structure-degradation relationship. Subsequently, we performed Degradation Cliff analysis and identified some key aspects conferring a positive contribution to activity, as well as some methodological limits when applying this approach to PROTACs. Linker structure degradation relationships were also investigated. Then, we built and characterized ternary complexes to validate previous results. Finally, we implemented machine learning classification models and showed that AR degradation for VHL-based but not CRBN-based PROTACs can be predicted from simple permeability-related 2D molecular descriptors.