Cytologic diagnosis and differential diagnosis of histiocytic signet ring cells in effusion specimens

Our plain-English summary of Cytologic diagnosis and differential diagnosis of histiocytic signet ring cells in effusion specimens, by M. Elahi, H. Lam, C. Adams, et al (CytoJournal, 2024).

The study

• Authors: M. Elahi, H. Lam, C. Adams, Q.K. Li
• Journal: CytoJournal
• Published: 2024;21:30
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Benign histiocytic proliferation in effusion specimens can be found in a variety of diseases such as rheumatoid arthritis, systemic lupus erythematosus, microorganism infections, trauma, reactive eosinophilic pleuritis, and others. In addition, nodular histiocytic/mesothelial hyperplasia is another well-recognized rare cause. The previous studies have shown that proliferative histiocytes have raisinoid nuclei and abundant eosinophilic granular cytoplasm and can be confused with malignant lesions, especially metastatic carcinomas. In this study, we evaluated the cytomorphology of benign histiocytes, discussed the diagnosis and differential diagnosis, and the clinical significance of histiocytic signet ring cells in effusion cytology.

Material And Methods: Seven hundred and fifty-five benign effusion cases (433 pleural effusions and 322 abdominal fluids) were found over 1 year. Among benign cases, 35 cases (28 pleural effusions and seven abdominal fluids) were included with findings of dominantly histiocytic signet ring cell morphology as well as immunohistochemical (IHC) stains. The clinical findings were also correlated.

Results: In contrast to the well-documented cytomorphology of raisinoid nuclei and eosinophilic cytoplasm of proliferative histiocytes in previous studies, we find that these cells predominately presented as signet ring cell morphology with clear cytoplasm. The most characteristic findings of benign histiocytes in pleural effusions are: (1) cells are arranged in sheets and/or scattered individual cells, but no two- or three-dimensional cell clusters; (2) cells are intermediate in size and with normal N/C ratio; (3) cells have eccentric located nuclei and abundant clear cytoplasm, giving signet ring cell appearance; (4) nuclei have fine granular chromatin pattern, no hyperchromia or coarse chromatin pattern, no nuclear atypia; and (5) immunohistochemical (IHC) stains demonstrate a strongly positivity for macrophage-histiocyte lineage marker CD68, but negativity for epithelial markers and mesothelial markers. Clinically, these patients do not demonstrate nodularity or lesions in the mesothelial lining of serous cavities.

Conclusion: Our study provides a detailed characterization of benign histiocytic signet ring cells in effusion cytology. The differential diagnosis of histiocytic signet ring cells is broad. The most important differential diagnoses are metastatic adenocarcinoma and epithelioid signet ring cell mesothelioma. The accurate diagnosis is critical for the appropriate clinical management of the patient. Cytopathologists should be aware of the diagnostic pitfalls of benign histiocytic signet ring cells in effusion samples in daily practice.

© 2024 The Author(s). Published by Scientific Scholar.

In plain English

This was a retrospective study of non-cancerous fluid samples from the chest (pleural effusions) and abdomen. It looked at histiocytes, a kind of immune cell that can look like cancerous 'signet ring' cells under the microscope. The authors searched one year of laboratory files and found 755 cases (433 pleural, 322 abdominal). They included 35 benign cases (28 pleural, 7 abdominal) in which histiocytic signet ring cells dominated and special stains had been done. In these cases the cells lay in sheets or as single cells, had clear cytoplasm, and stained positive for CD68, a histiocyte marker. Fourteen of 35 patients had a history of cancer. None showed nodules or lesions in the lining of body cavities on imaging. Only one benign pleural effusion showed the 'raisinoid' look described in earlier reports. For comparison, the authors described epithelioid signet ring cell mesothelioma, whose cells stained positive for calretinin. They concluded that the main look-alikes are metastatic adenocarcinoma and epithelioid signet ring cell mesothelioma. They noted a limited number of cases and no long-term follow-up of patients with a history of cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective cytomorphologic study (case series of effusion specimens with immunohistochemical staining)
• Who was studied: From 755 effusion cases (433 pleural effusions, 322 abdominal fluids) found in one year of cytopathology files at The Johns Hopkins Hospital, 35 benign cases (28 pleural effusions, 7 abdominal fluids) with mainly histiocytic signet ring cells and immunohistochemical stains. Patients were aged 36 to 75 years (median 64). Calendar years are not stated.
• Main results:
  • In the 35 benign cases, the histiocytes had off-center nuclei and abundant clear cytoplasm, giving a signet ring cell appearance. They were arranged in sheets or as scattered single cells, without two- or three-dimensional clusters.
  • In the benign effusions, the histiocytes stained diffusely positive for CD68 and negative for calretinin (a mesothelial marker) and claudin 4 (an epithelial marker).
  • Among the 35 patients, 14 of 35 (40.0%) had a history of malignancy, 12 of 35 (34.3%) cardiovascular disease, 4 of 35 (11.4%) chronic kidney disease and 3 of 35 (8.6%) chronic liver disease.
  • None of the 35 patients showed nodularity or lesions in the lining of the serous cavities on imaging.
  • Only one benign pleural effusion showed the raisinoid nuclei and eosinophilic granular cytoplasm described in previous studies.
  • In the epithelioid signet ring cell mesothelioma described for comparison, tumor cells formed three-dimensional clusters and stained diffusely positive for calretinin, but negative for CD68 and claudin 4. The number of mesothelioma cases is not given.
• The authors' conclusion: The authors concluded that benign histiocytic signet ring cells can resemble cancer in effusion samples. They identified metastatic adenocarcinoma and epithelioid signet ring cell mesothelioma as the most important differential diagnoses, and said cytopathologists should be aware of this diagnostic pitfall.
• Limitations the authors state:
  • Limited number of cases and no long-term follow-up of patients with a history of malignancy.

Topics

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Eosinophilic, Reactive Mesothelial Hyperplasia, Carcinoma, Cytology, Pleural Effusion, Nuclear Atypia, Macrophage.

Related studies

• The applicability of a keratin 7 monoclonal antibody in routinely Papanicolaou-stained cytologic specimens for the differential diagnosis of carcinomas — J.H. Baars, J.L. De Ruijter, et al. (1994)
• "Signet-ring" cells--a caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report — B. Rekhi, S. Pathuthara, et al. (2010)
• Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16 — K. Hiroshima, D. Wu, et al. (2016)
• Mesothelioma with signet-ring cell features: report of 23 cases — N.G. Ordóñez (2013)
• Signet ring cell mesothelioma; A diagnostic challenge — H. Wang, C. Herath (2019)
• Pulmonary acantholytic squamous cell carcinoma with focal signet ring cell morphology mimicking malignant mesothelioma on fine needle aspiration cytology: a case report — S.E. Choi, H.S. Park (2016)

Browse more research in CytoJournal, or return to medical research.