BAC Slide Club: Three Challenging Cytology Cases
The BAC's August lunchtime Slide Club featured three thought-provoking cases presented by Anthony Maddox and Leonie Wheeldon, highlighting the value of careful morphological assessment, appropriate ancillary testing and close clinical correlation.
The cases ranged from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), to an unusual ovarian/adnexal case with striking ciliated cells in ascitic fluid, and finally a lung cancer case in which two distinct tumour populations were identified in different mediastinal lymph nodes. Together, they demonstrated how cytology can uncover unexpected pathology and influence patient management.
Breast implant-associated anaplastic large cell lymphoma
The first case, presented by Anthony Maddox, involved a 59-year-old woman with previous cosmetic breast implants and a history of grade 1 lobular carcinoma of the left breast, which had been resected. She subsequently developed an effusion around the contralateral breast implant.
The initial thin-preparation specimen was poorly cellular and contained abundant proteinaceous material, with only occasional cells of uncertain significance. The cell block was more informative, showing an unusual population of atypical cells amid necrotic and degenerative material. Some cells had multiple nuclei, including horseshoe-shaped nuclear arrangements, with prominent nucleoli.
Given the clinical history and morphology, anaplastic large cell lymphoma was an important consideration, alongside recurrent carcinoma. Immunocytochemistry was decisive: the atypical cells showed strong CD30 expression. CD3 was positive in a proportion of the cells, consistent with the known tendency of anaplastic large cell lymphoma to show variable expression of T-cell antigens, while CD68 highlighted only background macrophages.
The case reinforced an important practical point: peri-implant effusions should not automatically trigger a CD30 stain. The morphology and clinical context should guide the work-up. Where an atypical population is identified, a good cytology preparation and cell block, followed by appropriate immunocytochemistry and specialist haematopathology review, are essential.
An unusual ovarian/adnexal case with ciliated cells in ascitic fluid
The second case was deliberately left as a diagnostic work in progress. A 59-year-old woman presented with ascites, and CT demonstrated a large, partially cystic left adnexal mass measuring up to approximately 20 cm.
The ascitic fluid showed a striking population of single cells with variable size and shape. On closer examination, some showed signet-ring morphology, while others displayed prominent ciliation. Numerous ciliated cells were present, with evidence that some had lost their cilia into the background.
The morphology was not entirely typical of a low-grade process: some cells showed atypical nuclear features, and the signet-ring cells could appear quite high grade. The initial biopsy suggested a low-grade tumour, but the cytological findings raised the possibility of a more complex picture, including the potential for different grades or components.
The case remains under investigation, with further immunohistochemistry and correlation with the ovarian/adnexal biopsy planned. The unusual presence of ciliated cells in ascitic fluid provided a memorable example of the distinctive appearances that can be encountered in serous fluid cytology.
Two different lung tumours identified in separate mediastinal lymph nodes
Leonie Wheeldon's case involved a 61-year-old woman referred through a lung cancer screening programme after a lesion was identified in the left upper lobe, with a further right middle lobe nodule. PET imaging demonstrated avid left hilar and mediastinal lymph nodes together with multiple bone metastases. EBUS was undertaken for diagnosis.
Sampling the 4L node produced diagnostic malignant cells, although the specimen contained considerable benign bronchial contamination. The tumour cells showed marked nuclear pleomorphism and abundant cytoplasm and were initially favoured to represent adenocarcinoma. Obtaining sufficient tumour for molecular testing was challenging because of the amount of contaminating material, prompting sampling of additional lymph nodes.
The 10L node produced a very different-looking population of cells, with scant cytoplasm, nuclear moulding and linear rosetting suggestive of neuroendocrine differentiation. This raised the possibility that the patient had two distinct tumour populations rather than a single tumour with variable morphology.
Immunocytochemistry supported the morphological distinction. Both populations were TTF-1 positive and P40 negative, but synaptophysin and chromogranin were negative in the 4R/4L tumour and strongly positive in the 10L tumour. The final interpretation was lung adenocarcinoma in the 4R and 4L nodes, with a large cell neuroendocrine carcinoma in the 10L node.
The distinction was clinically important because the two tumour types had different molecular profiles. PD-L1 expression was 95% in the adenocarcinoma and 5% in the large cell neuroendocrine carcinoma. KRAS G12C was identified in the adenocarcinoma, while the neuroendocrine carcinoma harboured a KRAS G12V mutation. The findings were presented to the multidisciplinary team, and treatment was directed towards the neuroendocrine component with chemotherapy combined with immunotherapy, including pembrolizumab.
The case demonstrated the importance of recognising a morphological discrepancy rather than assuming that all malignant cells in a patient necessarily represent the same tumour. Had sampling stopped after the initial diagnostic material was obtained, the second tumour would not have been identified. The case highlights the value of investigating unexpected morphological differences when they arise.
Key learning points
• Clinical history remains critical. Previous malignancy, breast implants, an unusual effusion or unexpected imaging findings can materially alter the differential diagnosis.
• Morphology should drive ancillary testing. A CD30 stain, for example, is most useful when the clinical and cytological findings raise the possibility of BIA-ALCL.
• A good cell block can be decisive when a direct cytology preparation is sparsely cellular or obscured by degeneration and background material.
• When the morphology does not fit the initial diagnosis, broaden the immunocytochemical panel rather than forcing the cells into the first diagnostic category considered.
• Different tumour populations in different samples may represent genuinely different neoplasms. Morphological differences should not be dismissed simply because a patient already has an established diagnosis.
• Cytology findings can directly affect clinical management, particularly when they identify distinct tumour types with different molecular profiles and treatment implications.
A valuable reminder of the strengths of Slide Club
The August Slide Club provided an excellent demonstration of why challenging cases remain such a valuable part of professional learning. From recognising BIA-ALCL in an implant-associated effusion, through an unresolved ovarian case with an unusual ciliated population, to identifying two distinct lung malignancies in separate lymph nodes, the cases emphasised the importance of looking closely, questioning unexpected findings and using ancillary investigations to answer specific morphological questions.
The session also highlighted the practical value of multidisciplinary discussion. In the lung case, continued dialogue between cytology, respiratory and oncology teams helped establish the significance of the differing tumour populations and supported a treatment strategy tailored to the patient's disease.