Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms

Abstract

Objective: To retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China.

Methods: A retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis.

Results: In total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common.

Conclusion: The accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

Keywords: Haematolymphoid; accurate diagnosis; diagnostic pitfalls; expert review; lymphoma; misdiagnosis; pathology.

Figure 1

Misdiagnosis analysis of 2291 cases.

Figure 2

Poorly fixed lymph node. (A) Under low magnification, the lymph nodes is well stained in the periphery and lightly stained in the center (×5.5); (B) The structure near the capsule is well preserved, and the cell morphology is good (×400); (C) The tissue is dissociated, and the cells are shrunken in the area away from the capsule (×400).

Figure 3

The impact of the thickness of the HE section on morphological observation (×400). (A) The previously prepared slice (at another hospital) is thick, with a medium cell volume and unclear structure; (B) The reprepared slice (at our hospital) is thin, with a clear cellular detail and larger volume.

Figure 4

Immunostains and interpretation (×400). (A) In original sections made by other hospitals, CD3 staining is difficult to interpret; (B) After restaining in our hospital, the CD3 results were positive in the cytoplasm; (C) In original sections made by other hospitals, CD19 showed positive signals but was located in the nucleus; (D) After restaining in our hospital, CD19 was found to be negative in tumor cells, and positive signals of the internal controls were localized on the cell membrane.

Figure 5

Dual-staining with EBER (nuclear stain in brown) and CD3/CD20 (membranous and cytoplasmic in red) (×400). (A) EBER/CD3 dual-staining showed no dual-staining positive cells; (B) EBER/CD20 dual-staining demonstrated dual-positive cells.

Figure 6

Typical Castleman disease. (A) Follicles with atrophic germinal centers and expanded mantle zones, forming a concentric annular structure, with an “onion-skin” look (×150); (B) Multiple germinal centers within a single mantle area (×65); (C) A remarkable hyalinized vessel grows into the germinal centers, forming a “lollipop” appearance (×200); (D) Sheets of plasma cells are seen in the interfollicular region in PC-type CD (×200).

Figure 7

Misdiagnosed metastatic carcinoma. (A, B) In HE sections, there was significant histiocytic proliferation, atypical cells with large nuclei, and unremarkable epithelioid structure (A ×200, B ×300); (C) CKpan staining was positive in tumor cells (×300); (D) CD163 staining was positive in histiocytes (×300).