The Second Report of Posterior Mediastinal Müllerian Cyst in a Male Patient

Abstract

Following the recent first report of a posterior mediastinal Müllerian cyst in a male patient (Mihara et al, 2026), we present the second documented male patient, confirming that this entity, previously considered exclusive to women since the 2005 description by Hattori, can indeed occur in men. A 51-year-old man was incidentally found to have a posterior mediastinal cyst during cardiac computed tomography. The 3.5 × 3 × 5.5 cm³ cyst at T4-T7 was resected via robotic-assisted thoracoscopy. Immunohistochemistry confirmed Müllerian differentiation (estrogen receptor+/progesterone receptor+/PAX8+/WT1+). This second male patient establishes that posterior mediastinal Müllerian cysts should be considered in the differential diagnosis of mediastinal cystic lesions regardless of patient sex.

Introduction

In 2005, Hattori described ciliated cysts in the posterior mediastinum of 3 women, characterized by their unique hormone receptor positivity and Müllerian differentiation. ¹ For nearly 2 decades, approximately 45 patients were reported, exclusively women aged 18 to 60 years, establishing these “cysts of Hattori” as an entity seemingly specific to women. ² This female patient predominance was attributed to the fact that Müllerian duct regression in men, mediated by anti-Müllerian hormone, typically eliminates these structures during embryogenesis. ³ However, when Müllerian remnants do occur in men, they manifest as persistent Müllerian duct syndrome (PMDS) with Müllerian tissue confined to pelvic, inguinal, and scrotal locations. ⁴ The posterior mediastinum, where embryonic Müllerian ducts originate before descending caudally, ⁵ was therefore considered an exclusive site for Müllerian remnants in female patients until Mihara et al recently reported the first male patient. ⁶ We present the second documented male patient, providing independent confirmation that incomplete cranial Müllerian regression can occur in the posterior mediastinum despite normal male sexual development.

Case Report

A 51-year-old man with a medical history of hypertension underwent cardiac computed tomography for cardiovascular risk assessment after a carotid ultrasound showed arterial calcification. The cardiac study incidentally revealed a posterior mediastinal mass, prompting further investigation with magnetic resonance imaging (MRI). MRI for further characterization demonstrated a well-circumscribed, 3.5 × 3 × 5.5 cm³ fluid-attenuating mass in the posterior mediastinum spanning Th4-Th7 vertebral levels, with mass effect on the descending aorta without hemodynamic compromise (Figure 1a and b). Given the size and location of the lesion, surgical resection was recommended for definitive diagnosis.

Figure 1.

MR imaging. (a) Axial T2-weighted magnetic resonance image of the chest showing a 3.5 × 3.0 cm² thin-walled cystic structure in the left paravertebral region, located posterior to the descending aorta. (b) Coronal view demonstrating a craniocaudal extension of approximately 5.5 cm, spanning from the level of the T4/T5 to the T6/T7 intervertebral spaces.

The patient underwent robotic-assisted thoracoscopic resection without complication. Using bipolar energy, the cyst was dissected from the descending aorta together with a portion of the aortic adventitia to ensure complete excision. Careful further dissection allowed removal of the cyst en bloc, including the surrounding pleura parietalis. The specimen was extracted intact through one of the robotic ports.

Grossly, the specimen consisted of a thin-walled cystic structure containing serous fluid. Microscopic examination revealed a cyst lined by slightly folded cuboidal to columnar epithelium with scattered ciliated cells, surrounded by a thin smooth muscle wall (Figure 2a and b). No atypia, mitotic activity, or endometrial stroma was identified. Immunohistochemical analysis demonstrated strong nuclear positivity for PAX8 and WT1 (Figure 2c and d), with positive staining for estrogen receptor (ESR1) and progesterone receptor (PGR) in the epithelial lining (Figure 2e and f). The epithelium was also positive for keratin 7 (KRT7), epithelial membrane antigen (MUC1), and claudin 4 (CLDN4) (Supplemental Figure S1a-c), while staining was negative for calretinin (CALB2) and TTF-1 (NKX2-1) (Figure 2g and h). Fluorescence in situ hybridization (FISH) analysis of the cystic tissue using centromeric probes for chromosomes X and Y confirmed the presence of both sex chromosomes, providing direct molecular confirmation of male biological sex at the tissue level (Supplemental Figure S1d and e).

Figure 2.

Histopathological and immunohistochemical findings. (a) Hematoxylin and eosin staining showing the cyst lined by cuboidal to columnar epithelium (200×). (b) Higher magnification showing scattered ciliated cells (black arrowheads; 400×). (c) Nuclear positivity for PAX8 in the epithelial lining (200×). (d)Nuclear positivity for WT1 (200×). (e)Estrogen receptor (ESR1) showing nuclear positivity (200×). (f) Progesterone receptor (PGR) demonstrating nuclear positivity (200×). (g)Calretinin (CALB2) showing negative staining. (h) TTF-1 (NKX2-1) showing negative staining (200×).

The patient had an uncomplicated postoperative course and was discharged on the first postoperative day. At the 2-week follow-up, he remained clinically well with no postoperative complications. The patient subsequently reported continued well-being and absence of complications 1 year after surgery.

Discussion

We present the second reported male patient with a posterior mediastinal Müllerian cyst (cyst of Hattori), providing independent confirmation of the recent patient reported by Mihara et al, ⁶ suggesting broader sex distribution than previously recognized.

Comparison with the patient reported by Mihara et al reveals both similarities and differences (Table 1). Both patients were middle-aged men with incidentally discovered cysts showing identical immunohistochemical profiles (estrogen receptor+/progesterone receptor+/PAX8+/WT1+). Male biological sex was confirmed in both patients through molecular analysis, with Mihara et al performing peripheral blood karyotyping (46,XY) and our patient demonstrating XY status through FISH on the cystic tissue itself. The cysts were similar in size, though in our patient occurred at a higher vertebral level (T4-T7 vs T7-T8). Both patients were successfully treated with minimally invasive surgery, though we employed robotic assistance while Mihara used conventional video-assisted thoracoscopic surgery. Neither patient showed evidence of sexual development disorders or PMDS.

Table 1.

Comparison of Clinical, Radiological, Surgical, and Pathological Features Between the Patient Reported by Mihara et al and the Present Patient.

Feature	Mihara Et Al (2025)	Present Patient
Age (years)	46	51
Presentation	Incidental (routine check-up)	Incidental (cardiac computed tomography)
Cyst size	6.0 cm	3.5 × 3 × 5.5 cm
Vertebral level	T7-T8	T4-T7
Surgical approach	Video-assisted thoracoscopic surgery	Robotic-assisted thoracoscopic surgery
Estrogen receptor (ESR1)	Positive	Positive
Progesterone receptor (PGR)	Positive	Positive
PAX8	Positive	Positive
WT1	Not reported	Positive
Keratin 7 (KRT7)	Not reported	Positive
Claudin 4 (CLDN4)	Not reported	Positive
TTF-1 (NKX2-1)	Negative	Negative
Calretinin (CALB2)	Not reported	Negative
Complications	None	None
Hospital stay (days)	Not specified	1
Follow-up	4 years, no recurrence	1 year, no recurrence
Karyotype	Karyotype 46, XY (peripheral blood)	Fluorescence in situ hybridization XY (cystic tissue)

From an imaging perspective, the primary anatomical location of the cyst represents the most important clue for differential diagnosis, as these entities may present with similar computed tomography and MRI signal characteristics.^7,8 Bronchogenic cysts are most commonly located in the subcarinal region, while esophageal duplication cysts are typically found adjacent to the esophagus. Mesothelial cysts characteristically occur in the cardiophrenic angle. Both Hattori cysts and neurenteric cysts typically present in the paravertebral region, with associated vertebral anomalies serving as the distinguishing radiological feature of neurenteric cysts. As in our patient, definitive diagnosis of Hattori cyst typically requires postoperative histopathological and immunohistochemical analysis, as preoperative imaging features alone cannot reliably distinguish this entity from other paravertebral cysts.

The occurrence in male patients raises embryological questions. During normal male development, anti-Müllerian hormone is secreted by Sertoli cells causing regression of Müllerian ducts by the 8th gestational week. ³ However, incomplete regression can result in persistent Müllerian remnants, typically as prostatic utricle cysts or inguinal Müllerian duct cysts associated with PMDS. ⁴ These 2 patients suggest that Müllerian tissue can also persist in the thoracic region where the cranial portion of the Müllerian duct originates near the 3rd to 5th thoracic vertebrae during embryogenesis. ⁵ Whether our patient had subtle abnormalities in anti-Müllerian hormone signaling ⁹ or represents random incomplete regression remains unknown. Genetic testing was not performed.

While previous literature emphasized women’s exclusiveness, ² the recent identification of 2 male patients establishes that cyst of Hattori should be considered in the differential diagnosis of posterior mediastinal cysts regardless of sex. The immunohistochemical profile remains the definitive diagnostic tool, distinguishing these cysts from bronchogenic cysts (estrogen receptor/progesterone receptor negative) and mesothelial cysts (calretinin positive). ¹⁰ The occurrence of 2 male patients within a short timeframe suggests that this entity may have been underrecognized in men due to diagnostic bias rather than true biological exclusivity. Further investigation into male patients with posterior mediastinal cysts, particularly with routine application of Müllerian markers when ciliated epithelium is identified, may reveal additional occurrences.

Supplemental Material

sj-pdf-1-ijs-10.1177_10668969261458404 - Supplemental material for The Second Report of Posterior Mediastinal Müllerian Cyst in a Male Patient

Supplemental material, sj-pdf-1-ijs-10.1177_10668969261458404 for The Second Report of Posterior Mediastinal Müllerian Cyst in a Male Patient by Andreas Tiefenbacher, José Ramón Matilla, Helmut Prosch and Luka Brčić in International Journal of Surgical Pathology

Supplemental Material

sj-docx-2-ijs-10.1177_10668969261458404 - Supplemental material for The Second Report of Posterior Mediastinal Müllerian Cyst in a Male Patient

Supplemental material, sj-docx-2-ijs-10.1177_10668969261458404 for The Second Report of Posterior Mediastinal Müllerian Cyst in a Male Patient by Andreas Tiefenbacher, José Ramón Matilla, Helmut Prosch and Luka Brčić in International Journal of Surgical Pathology