Intraductal papillary mucinous neoplasms of the pancreas: Cytologic-histologic correlation study and evaluation of the cytologic accuracy in identifying high-grade dysplasia/invasive adenocarcinoma

Abstract

Objective: Intraductal papillary mucinous neoplasms (IPMNs) may be associated with invasive adenocarcinoma, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). We aimed to review the cytologic-histologic correlation of cases with a histologic diagnosis of IPMN.

Material and methods: A database search (January 2010-January 2021) was performed for resected IPMNs with preceding endoscopic ultrasound-guided fine-needle aspiration (FNA). Cytology slides were reviewed for the presence of benign, atypical, or malignant cells, and necrosis. Histologically, IPMNs were classified as benign (LGD) or malignant (HGD or adenocarcinoma).

Results: There were 41 patients with IPMN; 24 malignant and 17 benign. Sixteen of the 24 malignant IPMNs were accurately classified as malignant on cytology. There were eight false negatives and one false positive. Cytology yielded a sensitivity of 67% and a specificity of 94%. Among the 16 true positives with FNA diagnosis of adenocarcinoma, seven were IPMNs with HGD, and nine had invasive adenocarcinomas on histology. Cellular morphology and absence or presence of necrosis did not help distinguish HGD from adenocarcinoma on cytology (P > 0.5). Sampling errors and interpretative errors resulted in false-negative cases. Cytology yielded diagnoses related to IPMN in 73% of cases (30/41) and lack of identification of mucinous cells/mucinous background resulted in interpretative errors (9).

Conclusion: This study shows that there is a good correlation between cytopathology and surgical pathology diagnoses of IPMNs and that cytology is mostly able to recognize IPMN with HGD/adenocarcinoma. However, heterogeneity in areas of IPMN with HGD/adenocarcinoma may result in sampling errors yielding false-negative cases. Mucinous cells/background should raise the suspicion of IPMN on cytology, even when no neoplastic epithelium is present for the evaluation of dysplasia.

Keywords: Adenocarcinoma; Fine-needle aspiration; High-grade dysplasia; Intraductal papillary mucinous neoplasm; Pancreas.

Figure 1:

(a) An intraductal papillary mucinous neoplasm (IPMN) diagnosed on cytology (Diff-Quik stain, 100x). (b) Follow up histology confirmed the diagnosis of IPMN (Hematoxylin & eosin stain, 200x). (c) A case diagnosed as neoplastic mucinous cyst demonstrated mucinous background and rare fragment of gastric epithelium on cytology smears (Papanicoloau stain, 200x). (d) IPMN with low-grade dysplasia was noted in the resection specimen (Hematoxylin & eosin 200x). (e) An adenocarcinoma diagnosis on cytology (Papanicoloau stain, 200x). (f) IPMN with high-grade dysplasia was noted in subsequent histology (Hematoxylin & eosin stain, 200x).

Figure 2:

Findings usually missed in the discrepant cases with interpretative errors: (a) Mucinous epithelium, (Diff-Quik stain 200x) and (b) mucinous background (Papanicoloau stain, 200x).

Figure 3:

(a) A case showing necrosis in the cytology cell block, (Hematoxylin and eosin, 100x). (b) Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) (markedly atypical cells with loss of polarity) was noted in subsequent resection (Hematoxylin and eosin, 200x). (c) An adenocarcinoma diagnosis on cytology (high N: C ratio, mitoses, marked nuclear atypia, (Papanicoloau stain 200x)) (d) IPMN with HGD was noted on follow up resection. (complex papillary proliferation of tumor cells) (Hematoxylin and eosin, 100x). (e) False-negative case (sampling error): It was diagnosed on cytology as benign (Papanicoloau stain, 400x). (f) An invasive adenocarcinoma was noted in resection (Hematoxylin and eosin, 200x). (g) False-negative case (interpretative error): It was diagnosed on cytology as negative for malignancy. On review, mucin, necrosis, and atypical cells with high a N: C ratio were seen (Papanicoloau stain, 200x). (h) Histology showed IPMN with HGD, (Hematoxylin and eosin, 400x). (i) False-positive case: This case was suspicious for adenocarcinoma on cytology (prominent nucleoli and nuclear overlapping) (Hematoxylin and eosin, 400x) (j) Histology showed IPMN with low-grade dysplasia. The area with high-grade features was presumably not sampled on histology, (Hematoxylin and eosin, 200x).