Baker's rhinitis and asthma with concomitant wheat anaphylaxis: a rare overlap of clinical entities / Rinite e asma do padeiro com anafilaxia após ingestão de trigo: um caso raro de sobreposição de entidades clínicas

Wheat is one of the fundamental sources of food worldwide. Baker's asthma and occupational rhinitis are both frequent and can be attributable to work exposure in bakers. However, the association between baker's asthma and wheat allergy is very rare. The authors report the case of a bakery worker who developed baker's asthma and occupational rhinitis after years of working in a bakery and later developed anaphylactic reactions after wheat ingestion.

O trigo é uma das fontes alimentares mais importantes em todo o mundo. A asma do padeiro e a rinite ocupacional são frequentes e podem ser atribuídas à exposição a farinhas em padeiros. No entanto, a associação entre asma do padeiro e alergia alimentar ao trigo é muito rara. Os autores descrevem um caso em que um trabalhador de panificação desenvolveu asma do padeiro e rinite ocupacional após anos trabalhando em uma padaria, e posteriormente desenvolveu reações anafiláticas após a ingestão de trigo.

Anafilaxia à lapa: um caso clínico raro / Limpet anaphylaxis: a rare case

A lapa (Patella vulgata) é um molusco frequentemente encontrado em regiões costeiras com clima quente. A alergia alimentar à lapa é muito rara, com poucos casos descritos na literatura. Os autores descrevem um caso de anafilaxia à lapa, com evidência de reação de hipersensibilidade do tipo I, através de IgE específica positiva à lapa, tanto com métodos in vivo, como in vitro.

Limpet (Patella vulgata) is a mollusk mainly found in warm coastal regions. Limpet allergy is considered rare, and few cases can be found in the literature. We describe a clinical case of limpet anaphylaxis, including in vitro and in vivo evidence of IgE mechanism involvement.

Histopathological correlations and fat replacement imaging patterns in recessive limb-girdle muscular dystrophy type 12.

BACKGROUND: Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown. METHODS: We included 27 adult patients with LGMDR12 and 27 age-matched and sex-matched healthy controls and acquired 6-point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale. RESULTS: In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r = 0.85, P < 0.001) and vastus lateralis (r = 0.68, P = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo-distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P < 0.001), and different patterns of fat replacement within each of the muscles. CONCLUSIONS: We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.

Sarcomatoid Spermatocytic Tumour: Report of a Rare Case and Literature Review.

Spermatocytic tumour (ST) accounts for 1% of testicular germ cell tumours. It is an indolent neoplasm with good prognosis. In approximately 6% of STs, sarcomatous dedifferentiation may occur, portending an aggressive behaviour and representing a significant diagnostic challenge that can lead to its misdiagnosis. Herein, we report the clinicopathological features of a patient with a sarcomatoid spermatocytic tumor, initially diagnosed as mixed germ cell tumour, who was referred to our institution with lung metastases mainly composed of rhabdomyosarcomatous elements. This case report illustrates the importance of recognizing this entity for adequate management of these patients.

Selective terpene based therapeutic deep eutectic systems against colorectal cancer.

Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation, on the other hand, has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES anti-CRC therapeutic potential, their physico-chemical properties, bioavailability and bioactivity, were explored. Our results show that safranal:ibuprofen (3:1), safranal:ibuprofen (4:1) and menthol:ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. menthol:ibuprofen (3:1) anti-proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of reactive oxygen species (ROS) production, and induction of apoptosis via caspase-3. On the other hand, safranal:ibuprofen (3:1) and safafranal:ibuprofen (4:1) seem to prevent tumour expansion only through the induction of apoptosis via caspase-3. Besides, these systems present an increase in ibuprofen permeability, with menthol:ibuprofen (3:1) increasing also ibuprofen's solubility thus its overall bioavailability. Knowing that cancer is a huge problematic situation that requires alternative therapies with less side effects, improved efficacy, associated with less costs and environmentally friendly, a new opportunity emerges for DES to be part of the pharmaceutical industry.

Natural Deep Eutectic Solvent (NADES) Extraction Improves Polyphenol Yield and Antioxidant Activity of Wild Thyme (Thymus serpyllum L.) Extracts.

Wild thyme (Thymus serpyllum L.) herbal dust has been recognized as a potential underutilized resource for the recovery of antioxidants. The aim of this paper was to optimize natural deep eutectic solvent (NADES) extraction of polyphenols to obtain improved antioxidant activity of extracts determined by selected in vitro assays (DPPH, FRAP, and ABTS). Twenty different NADES systems were investigated in the first step of the screening of the extraction solvent and l-proline (Pro)-glycerine (Gly) based solvents provided the best results. Preliminary experiments organized by 25-1 fractional factorial design narrowed down the number of extraction factors from five (temperature, extraction time, NADES type, water content and L/S ratio) to three and determined their experimental domain for the final step. A face-centered central composite design with temperature (40-55-70 °C), extraction time (60-120-180 min) and L/S ratio (10-20-30 g NADES/g sample) was applied for influence analysis and process optimization. Multi-response optimization suggested a temperature of 65 °C, time of extraction of 180 min and L/S ratio of 28 g NADES/g DW as optimal extraction parameters. Experimental validation confirmed good agreement between experimental and predicted results in the extract obtained at optimal conditions and the interactions in the most suitable NADES (N16; Pro-Gly-H2O; 1:2:1) were confirmed by the 1H-NMR.

Benign Metastasizing Leiomyomatosis to the Skin and Lungs, Intravenous Leiomyomatosis, and Leiomyomatosis Peritonealis Disseminata: A Series of Five Cases.

Benign metastasizing leiomyomatosis (BML) is a rare disease that typically occurs in women with a history of uterine leiomyomatosis. Benign metastasizing leiomyomatosis occurs more frequently in the lungs but may also develop in other organs and tissues. Other unusual variants of extra-uterine leiomyomatosis include intravenous leiomyomatosis (IVL) and leiomyomatosis peritonealis disseminata (LPD). In this article, three cases of BML are presented. One case, in a premenopausal woman, presented cutaneous metastases. We also present a case of IVL and a case of LPD, which occurred in postmenopausal women. Given the rarity of BML, IVL, and LPD, the authors reviewed the literature and herein discuss the implications for treatment in all five cases. Evidence for treating BML, IVL, and LPD is still scarce, and data available from our series and other small series seem to point to the patient's hormonal status playing a fundamental part in the treatment plan. Furthermore, a collecting bag when performing excision of uterine leiomyomas may help avoid the potential spreading of leiomyomatosis. Hysterectomized patients with chronic cough, frequent respiratory infections, abdominal discomfort, right heart failure, or non-specific symptoms should be actively screened for BML, IVL, and LPD. Treatment should be individualized according to each patient's hormonal status and desires.

Simultaneous Hydrolysis of Ellagitannins and Extraction of Ellagic Acid from Defatted Raspberry Seeds Using Natural Deep Eutectic Solvents (NADES).

Defatted raspberry seeds were used as an alternative source of antioxidants and ellagic acid (EA) extracted using Natural deep eutectic solvents (NADES). In the preliminary study, the best NADES combination (citric acid-betaine) and the most influential variables (temperature, time, and NADES/plant ratio) were selected for the further optimization process. All samples were analyzed in terms of total polyphenol, EA content, and antioxidant activity. Two sets of optimal conditions were generated by response surface methodology. The first set (Opt1) was designed for higher conversion of ellagitannins to EA while the latter set (Opt2) for higher EA content/100 g extract. Opt1 and Opt2 had higher values for all investigated responses compared to 80% ethanolic extract but had a lower conversion rate of ellagitannins to EA compared to acidified methanol extract. The third set of parameters (Opt3) selected beyond the initial experimental domain was used to obtain a sample with the highest EA content/100 g extract. Due to their nature, NADES extracts are ready to use and could have various technological roles in products since they are antioxidants, acidifiers, and colorants. NADES raspberry extracts exhibited higher anti-proliferative activity compared to ethanolic extracts in terms of EC50 values. However, the main contributor of anti-cancer activity in NADES raspberry extracts were individual NADES compounds and/or their newly formed NADES structure.

Therapeutic Deep Eutectic Systems towards the Treatment of Tuberculosis and Colorectal Cancer: Opportunities and Challenges.

What if a new technology based on therapeutic deep eutectic systems would disrupt the current treatment of major economic and socially burden diseases? The classical definition of eutectic systems is that they are the combination of two or more compounds that interact via hydrogen bonds, from which results a melting temperature depression in comparison with that of its individual components. Therapeutic deep eutectic systems are defined as eutectic systems in which at least one of the individual components is an active pharmaceutical ingredient, or a eutectic system in which the active pharmaceutical ingredient is dissolved. Current literature reports on tuberculosis have been mostly based on the most common anti-tuberculosis drugs prescribed. Using eutectic systems based on naturally occurring molecules known for their anti-microbial activity may also present a promising therapeutic strategy able to cope with the prevalence of Mycobacterium tuberculosis and prevent the appearance of multidrug resistance strains. With regards to colorectal cancer, literature has been unravelling combinations of terpenes with anti-inflammatory drugs that are selectively cytotoxic towards colorectal cancer cells and do not compromise the viability of normal intestinal cells. This technology could contribute to preventing tumor growth and metastasis while providing a patient compliance therapeutics, which will be crucial to the success of overcoming the challenges presented by cancers.

Kaposi Sarcoma as Presentation of HIV - A Clinical Case.

Kaposi sarcoma (KS) is the most common neoplasm of people with human immunodeficiency virus (HIV) infection. Although, in the antiretroviral therapy (ART) era, KS is a rare form of presentation of HIV/acquired immunodeficiency syndrome. The authors present a case of disseminated KS in a 23-year-old male. Just after the diagnosis the patient started ART and then chemotherapy with placlitaxel with clinical improvement. This case is highly representative of the complexity of HIV. The authors aim to bring awareness of an unusual form of presentation of HIV, and recall the severity and the necessity of an early diagnosis and treatment.

Minimally invasive esophagectomy versus open esophagectomy: A systematic review and meta-analysis.

The paradigm of the treatment of esophageal cancer has been changing with the increasing use of minimally invasive esophagectomy (MIE) in detriment of open esophagectomy (OE). We aimed to perform a meta-analysis to evaluate and compare these two techniques in terms of mortality and associated complications. The literature search was conducted in MEDLINE and U.S. National Library of Medicine Clinical Trials, considering eligible articles since 2015 to 2020. Clinical trials and observational studies were included. We presented results as mean differences with 95% confidence intervals and calculation of heterogeneity associated to the included studies. Thirty-one articles were included with a total of 34,465 participants diagnosed with esophageal adenocarcinoma or squamous cell carcinoma. MIE had tendency towards a decrease in 30- and 90- day mortality after surgery, but no statistically significative results were found. Major cardiovascular and respiratory complications were less frequent in the MIE group, despite high heterogeneity. Also, MIE might contribute to a decrease of minor post-operative complications, to an increase need of a second surgical intervention, to a greater risk for vocal cord lesions; but these results were not statistically significant. Additionally, no differences were found concerning risk of wound infection and for local and systemic recurrence. MIE may be more beneficial than OE, but these findings should be considered carefully.

Binding of RuCp complexes with human apo-transferrin: fluorescence spectroscopy and molecular docking methods.

The interaction between human serum transferrin (hTf) and three promising organometallic Ru (II)- (η5-C5H5) derived complexes, that have already shown strong in vitro cytotoxicity towards human cancer cell lines, has been investigated using fluorescence spectroscopic techniques. The results suggested that the formation of Ru-hTf systems involves a dynamic collision. The binding process occurs spontaneously (ΔG < 0), mainly driven by hydrophobic interactions. Additional docking studies show that all complexes bind preferably to a specific hydrophobic pocket in the C2-subdomain as already observed for other metal-cyclopentadienyl (MCp) complexes and are in agreement with the experimental results. With these studies we hope to contribute to the understanding of the mechanism of action of these promising cytotoxic agents, thus providing clues for a more rational design.

Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists.

Low-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience.

BACKGROUND: Plexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1. METHODS: Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019). RESULTS: Nineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35-420 days). All but one had sustained clinical improvement, mainly in the first 60-90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension. CONCLUSIONS: In the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.

Recurrent midgut volvulus in an adult patient - The case for pexy? A case report and review of the literature.

INTRODUCTION: Intestinal malrotation is a rare condition, with an incidence estimated between 0,2 to 1%. Most cases are diagnosed and treated during childhood. Adult presentations are rare and most adults present with chronic nonspecific complaints. Midgut volvulus is the most feared complication of intestinal malrotation, far more common among the pediatric than the adult population. Presentation in adulthood with a midgut volvulus accounts for a minority of these patients (15%). The Ladd procedure is the standard surgical management of midgut volvulus and intestinal malrotation. Most evidence on the outcomes of the Ladd procedure originates from studies on pediatric population and the recurrence among children who have had a Ladd procedure is low (2-7%). PRESENTATION OF CASE: We report an exceedingly rare case of a patient who presented in adulthood with a midgut volvulus and less than two years after undergoing Ladd procedure presented with a recurrence of the midgut volvulus. The recurrent midgut volvulus was successfully treated by a fixation procedure (cecopexy and duodenopexy). CONCLUSION: Reports of midgut volvulus in adult patients are scarce and reports of recurrence even scarcer hence the rate of recurrence among adult patients has yet to be determined. The recurrence rate in some of the available adult series is much higher than the rate reported among children. Should the rate of recurrence among adult patients prove higher, it poses the question of whether the Ladd procedure should be modified to include bowel fixation when performed in adults.

Preparation of Binary and Ternary Deep Eutectic Systems.

The preparation of deep eutectic systems (DES) is a priori a simple procedure. By definition, two or more components are mixed together at a given molar ratio to form a DES. However, from our experience in the laboratory, there is a need to standardize the procedure to prepare, characterize and report the methodologies followed by different researchers, so that the results published can be reproduced. In this work, we test different approaches reported in the literature to prepare eutectic systems and evaluated the importance of water in the successful preparation of liquid systems at room temperature. These published eutectic systems were composed of citric acid, glucose, sucrose, malic acid, ß-alanine, L-tartaric acid and betaine and not all of preparation methods described could be reproduced. However, in some cases, it was possible to reproduce the systems described, with the inclusion of water as a third component of the eutectic mixture.

Glutamatergic Neurokinin 3 Receptor Neurons in the Median Preoptic Nucleus Modulate Heat-Defense Pathways in Female Mice.

We have proposed that arcuate neurons coexpressing kisspeptin, neurokinin B, and dynorphin (KNDy neurons) contribute to hot flushes via projections to neurokinin 3 receptor (NK3R)-expressing neurons in the median preoptic nucleus (MnPO). To characterize the thermoregulatory role of MnPO NK3R neurons in female mice, we ablated these neurons using injections of saporin toxin conjugated to a selective NK3R agonist. Loss of MnPO NK3R neurons increased the core temperature (TCORE) during the light phase, with the frequency distributions indicating a regulated shift in the balance point. The increase in TCORE in the ablated mice occurred despite changes in the ambient temperature and regardless of estrogen status. We next determined whether an acute increase in ambient temperature or higher TCORE would induce Fos in preoptic enhanced green fluorescent protein (EGFP)-immunoreactive neurons in Tacr3-EGFP mice. Fos activation was increased in the MnPO but no induction of Fos was found in NK3R (EGFP-immunoreactive) neurons. Thus, MnPO NK3R neurons are not activated by warm thermosensors in the skin or viscera and are not warm-sensitive neurons. Finally, RNAscope was used to determine whether Tacr3 (NK3R) mRNA was coexpressed with vesicular glutamate transporter 2 or vesicular γ-aminobutyric acid (GABA) transporter mRNA, markers of glutamatergic and GABAergic neurotransmission, respectively. In the MnPO, 94% of NK3R neurons were glutamatergic, but in the adjacent medial preoptic area, 97% of NK3R neurons were GABAergic. Thus, NK3R neurons in the MnPO are glutamatergic and play a role in reducing TCORE but are not activated by warm thermal stimuli (internal or external). These findings suggest that KNDy neurons modulate thermosensory pathways for heat defense indirectly via a subpopulation of glutamatergic MnPO neurons that express NK3R.

Fine-needle aspiration features of extraskeletal myxoid chondrosarcoma: A study of cytological and molecular features.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a tumor of uncertain differentiation. Few data are available regarding its cytomorphological features in fine-needle aspiration (FNA). Specific cytogenetic alterations involving the NR4A3 gene are found in EMC and can be identified in FNA samples. METHODS: We retrospectively reviewed 14 FNAs performed in 11 patients with an EMC; 10 FNAs were performed preoperatively on primary tumors; 2 were performed on recurrences and 2 were performed on metastasis. Cytological features were compared with histological findings. Immunohistochemistry (IHC) and molecular studies were performed both in FNA and histological specimens. RESULTS: A preoperative cytological diagnosis of EMC was rendered in eight FNAs performed in newly diagnosed tumors and in recurrent/metastatic cases. A descriptive diagnosis of a myxoid neoplasm was made in the remaining two cases. Smears were moderately hypercellular, composed of plasmocytoid to fusiform cells, with scant, pale cytoplasm, bland nuclei and inconspicuous nucleoli, dispersed as cords, strands and occasionally with a lace-like pattern, in an abundant chondromyxoid matrix. IHC performed showed focal positivity for S100 and NSE. Fluorescence in situ hybridization technique performed in three FNA specimens showed EWSR1 gene rearrangements in all, concomitant with NR4A3 gene rearrangement in one case. Histological specimens showed typical features of EMC and NR4A3 gene rearrangements were found in all cases tested. CONCLUSION: FNA cytology is a reliable method to perform a preoperative diagnosis of EMC regarding its cytomorphological and molecular features. Main differential diagnoses include myoepithelial tumors of soft tissue, myxoid liposarcoma and myxofibrosarcoma. Ancillary studies are helpful when coupled with cytomorphology evaluation.

Exploitation of new chalcones and 4H-chromenes as agents for cancer treatment.

Chalcone and chromene derivatives were synthesized in good yield through simple and effective reactions using innocuous solvents such as water and ethanol and high yielding aldol condensations. Generally, the reactions were performed at room temperature, leading to the isolation of highly pure compounds. These compounds were tested on breast cancer cells (MCF-7 and Hs578T) and breast non-neoplastic cells (MCF-10A). After determination of IC50 value, specific assays were performed to analyze the potential of these compounds, and those bearing halogenated substituents presented enhanced activity comparing to methoxyl or methyl groups. More specifically, the bromine atom was often present in the bioactive molecules that proceeded to the final assays and showed to be promising candidates for further studies. The selected chromene acted as a cell migration inhibitory agent and triggered regulated cell death associated with G2/M cell-arrest and microtubule destabilization. For chalcones, the results suggest an anti-proliferative activity. Also, results for combination-therapy potentiated the antitumor effect of doxorubicin and reduced cytotoxicity in MCF-10A cells.

Prepubertal gynaecomastia in a boy with Peutz-Jeghers syndrome: managing the aromatase overexpression.

Background Gynaecomastia, although rarely related to testicular tumours, in boys with Peutz-Jeghers syndrome (PJS) usually occurs due to large-cell calcifying Sertoli cell tumour (LCCSCT). Case presentation A 4-year-old boy, with a genetic diagnosis of PJS, presented gynaecomastia since the age of 2, associated with increased height velocity (HV). He exhibited bilateral breast enlargement (Tanner-B4) and a testicular volume of 4 mL. Testicular ultrasound revealed multifocal microcalcifications in both testicles. A laboratory evaluation showed undetectable gonadotrophins, testosterone and oestrogen and inhibin A of 4.6 pg/mL (0.9-1.7). The boy was subjected to therapy with anastrozole. In the last follow-up, 2 years after the start of therapy, he experienced a less tense Tanner-B2 and a decrease in HV; serum inhibin A had become negative. Conclusions This is one of the most precocious PJS-related gynaecomastia treated with aromatase inhibitors (AIs) reported in the literature. Oestrogen levels, although under the detection limit, may be sufficient to stimulate breast tissue/growth plates. Inhibin A is a good marker of LCCSCT and an indicator of response to AIs.