BAC Lunchtime Slide Club: Three Fascinating Mediastinal and Pulmonary Cytology Cases

At the October 2025 BAC Lunchtime Slide Club, Dr Anthony Maddox (West Hertfordshire Teaching Hospitals NHS Trust) and Mrs Leonie Wheeldon (Royal Cornwall Hospitals NHS Trust) shared three instructive cases, each highlighting different diagnostic and sampling challenges in thoracic cytopathology.

Case 1 – Benign Schwannoma of the Superior Mediastinum

A woman in her late fifties presented with a persistent cough and minor haemoptysis. Imaging revealed a well-circumscribed lesion in the superior mediastinum. Endoscopic ultrasound-guided FNA (EUS-FNA) showed a spindle-cell lesion with bland, elongated nuclei in a granular basophilic background.

A cell block confirmed spindle morphology without significant atypia or necrosis. Immunocytochemistry demonstrated:
• S100: positive
• D2-40: positive (supporting schwannoma)
• CD34 and STAT6: negative, excluding solitary fibrous tumour

The findings were diagnostic of a benign schwannoma. Surgical excision was under discussion given the patient’s comorbidities. This case illustrated the value of EUS-FNA with rapid on-site evaluation (ROSE) and targeted immunostaining in distinguishing spindle-cell mediastinal lesions.

Case 2 – Recurrent Combined Small- and Large-Cell Neuroendocrine Carcinoma

The second patient, a woman in her sixties with a history of a right upper-lobectomy for a combined neuroendocrine tumour, was found on PET-CT to have new mediastinal and hilar activity. EBUS-TBNA samples from stations 7 and 11R showed cohesive clusters of small to intermediate cells with scant cytoplasm, nuclear moulding, and granular “salt-and-pepper” chromatin.

Cell-block immunocytochemistry revealed:
• Synaptophysin and chromogranin: strongly positive
• CD56: negative
• Cytokeratin (MNF116): positive

The morphology and immunoprofile supported recurrence of a combined small-cell and large-cell neuroendocrine carcinoma, matching the previous resection (predominantly large-cell component). This case highlighted how even limited cytology samples can accurately identify tumour recurrence and demonstrate combined histology.

Case 3 – Combined Squamous and Neuroendocrine Carcinoma

Mrs Wheeldon presented an 81-year-old man with weight loss and exertional dyspnoea. Imaging showed a left-lung mass with mediastinal invasion. Initial bronchoscopy cytology was negative; therefore, EUS-FNA was performed.

At ROSE the first passes from the mass were largely necrotic. Sampling from station 7 was also necrotic with occasional atypical squamous cells. The laboratory preparations produced better material showing keratinised malignant cells with intracellular bridges—diagnostic of squamous cell carcinoma. However, a 19-gauge needle core from the main mass showed cells arranged in nests and ribbons with granular chromatin and prominent nucleoli.

Immunocytochemistry on the 19G needle cores from the mass demonstrated:
• TTF-1: positive
• P40: negative
• Synaptophysin and CD56: positive

The features indicated a combined tumour comprising both squamous and neuroendocrine components. PD-L1 testing on the squamous element was <1%. MDT consensus was to treat the patient initially for small-cell carcinoma, the more aggressive component. This case underscored the importance of multiple sampling approaches and large-bore needles when cytology and imaging appearances do not correlate.

Key Take-Home Messages

• Comprehensive sampling matters: multiple passes and cell-block preparation can reveal mixed morphology missed on initial smears.
• Targeted immunostains are crucial in resolving spindle-cell and neuroendocrine differentials.
• Combined tumours are rare but clinically significant, as management is guided by the most aggressive component.
• ROSE supports diagnostic adequacy, preventing non-representative sampling and unnecessary repeat procedures.