Turner syndrome (TS) is associated with delayed puberty, abnormal breast development, and increased risk of certain diseases. The purpose of this article is to present the current state of breast development assessment in TS patients, focusing on the use of ultrasound (US), mammography, and MRI, regarding their utility in monitoring changes in women with TS. A comprehensive literature review was conducted using databases like PubMed and Medline. There are currently no specific recommendations for breast US in TS patients, and because no conclusive US classification of breast development with distinctive sonographic features in the breast has been established, breast US in women with TS remains a diagnostic challenge. Proposed US scales for breast development in adolescent girls and fibroglandular tissue evaluation in men with gynecomastia are suggested as potential tools for monitoring breast development in women with Turner syndrome. Further research is highlighted as crucial to improving diagnostic and therapeutic approaches.

Diagnosing low-grade intraductal epithelial proliferations and distinguishing hyperplasia from neoplasia has traditionally relied on well-established morphological and immunophenotypic criteria. However, in routine practice, differentiating luminal epithelial proliferations that are not necessarily clonal from bona fide neoplastic precursor lesions remains challenging. In specific clinical scenarios, such as gynaecomastia, adolescent breast tissue and fibroepithelial lesions, epithelial proliferations may appear morphologically and immunophenotypically worrisome for neoplasia, yet the clinical context supports a non-neoplastic process. Rather than representing conventional clonal neoplasia, these changes may reflect hormonally driven or stromal-induced luminal differentiation and often lack the sharp demarcation typical of conventional neoplasia. This narrative review delineates these context-dependent diagnostic pitfalls and proposes an integrated framework that emphasises architectural features, clonal demarcation and the clinical setting. By positioning these borderline lesions within a biological continuum and refining diagnostic thresholds in context, this approach aims to improve diagnostic reproducibility, mitigate the risk of overdiagnosis and support appropriate, risk-adapted patient management.

Papillary breast lesions are a heterogeneous group of lesions with epithelial origin, composed predominantly of papillae, and they are particularly rare in men. Atypical papillary lesions are rare epithelial tumors, characterized by cytologic or architectural features that are not clearly benign but may fall short of definitive malignancy. Herein, we present a case of a 51-year-old man admitted with painless, hemorrhagic discharge from the left nipple. Ultrasonography revealed an intraductal solid mass in the left breast, along with mild bilateral gynecomastia. Core needle biopsy (CNB) subsequently confirmed an atypical papillary lesion. This case highlights the importance of imaging and tissue biopsy in establishing an accurate diagnosis, due to their wide spectrum of histological presentations from benign to malignant, which should be well differentiated.

Tuberous breast deformity is well described in females but remains rare in males, where it represents an uncommon morphological variant of gynecomastia. It is characterized by a constricted breast base, enlarged nipple-areolar complex (NAC), inframammary fold indentation, and apparent parenchymal herniation into the areola. We report the case of a 17-year-old male presenting with progressive bilateral breast enlargement since the age of 11, with marked worsening at 16 years and significant psychosocial distress. Clinical examination revealed bilateral glandular gynecomastia with enlarged NACs, mild asymmetry, and global base constriction consistent with a severe tuberous deformity. Ultrasonography showed homogeneous glandular hypertrophy, and endocrine evaluation was normal. Surgical correction using glandular transection and release of constricting elements resulted in satisfactory aesthetic outcomes without complications. Male tuberous breast deformity is an underrecognized entity requiring tailored surgical management addressing both glandular excess and base constriction.

Androgen insensitivity syndrome (AIS) is a group of complex clinical symptoms caused by X-linked genetic defects. It results from inactivating mutations in the androgen receptor (AR) gene, leading to hormone resistance in individuals with an XY karyotype despite normal androgen synthesis. We present a case of a 2-year-1-month-old boy who initially showed signs of incomplete masculinization of the external genitalia and underwent transverse preputial island flap urethroplasty during childhood. At the age of 7, he presented with gynecomastia, accompanied by accelerated growth and advanced bone age, with significantly elevated serum sex hormone levels. During this period, epididymitis recurred repeatedly. Genetic testing indicated a pathogenic mutation in the androgen receptor gene. The diagnosis of partial AIS with central precocious puberty was established, and treatment was initiated sequentially with oral letrozole and tamoxifen. The patient underwent multiple surgical procedures and experienced distress related to breast development. A review of the literature indicates that most patients with AIS present with delayed puberty; to date, only 2 cases of AIS combined with central precocious puberty have been reported. This case highlights diagnostic challenges, treatment considerations, and the importance of long-term multidisciplinary care, and further delineates the clinical phenotype.

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized by deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH), the central regulator of the reproductive axis. We report two siblings from a consanguineous family with CHH caused by a homozygous nonsense mutation (c.182C > A; p. Ser 61Ter) in exon 1 of KISS1R gene. The 15-years-old male proband presented with absent puberty, micropenis, and gynecomastia. Endocrine evaluation revealed low gonadotropin levels and brain magnetic resonance imaging (MRI) showed pituitary hypoplasia. His 12-years-old sister exhibited puberty delays, with absent breast development and pubic hair. The male patient received 1 year of pulsatile GnRH therapy, resulting in significant clinical improvements, including markedly increased testicular volume (from 0.9 to 5.6 mL), penile growth, and the resolution of gynecomastia. Notably, follow-up imaging demonstrated morphological recovery of the pituitary gland, with an increase in height from 3.5 to 4.5 mm, accompanied by the successful induction of spermatogenesis. This excellent response to GnRH underscores its efficacy in restoring fertility, particularly when initiated in early adolescence, and highlights the value of genetic diagnosis in consanguineous families.

Hyperprolactinaemia is a common adverse effect of antipsychotic medication, primarily resulting from dopamine D2 receptor blockade. It is characterised by menstrual irregularities, gynaecomastia, galactorrhoea and, with prolonged exposure, an increased risk of osteoporosis and breast cancer. When switching towards a prolactin-sparing antipsychotic is not feasible, adjunctive use of aripiprazole - a dopamine D2 partial agonist - has emerged as a validated strategy to mitigate hyperprolactinaemia without compromising antipsychotic efficacy. However, alternative options are needed for patients who cannot tolerate aripiprazole. Here we report the use of brexpiprazole, a dopamine D2 partial agonist structurally related to aripiprazole, to counteract paliperidone-induced hyperprolactinaemia effectively in a patient who developed a cutaneous reaction to aripiprazole. During the follow-up period with adjunctive brexpiprazole in combination with paliperidone, neither a recurrence of psychotic symptoms nor a reappearance of the skin reaction previously experienced with aripiprazole was observed.