Journal of Pathology and Translational Medicine

Case Study

Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors: Chankyung Kim, Yang-Guk Chung, Chan Kwon Jung; J Pathol Transl Med. 2023;57(5):278-283. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.07.13

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Abstract PDF: Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

Original Articles

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors: Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim; J Pathol Transl Med. 2015;49(1):23-29. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.08

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Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

Citations

Citations to this article as recorded by

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms
Gaoxiu Qi, Jinmeng Liu, Shuqi Tao, Wenyuan Fan, Haoning Zheng, Meihong Wang, Hanchao Yang, Yongting Liu, Huancai Liu, Fenghua Zhou
PeerJ.2023; 11: e15675. CrossRef
Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection
Emilie E. Vomhof-DeKrey, Jack T. Lansing, Diane C. Darland, Josey Umthun, Allie D. Stover, Christopher Brown, Marc D. Basson
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(2): G136. CrossRef
Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies
Napaporn Puripat, Kongsak Loharamtaweethong
Virchows Archiv.2019; 474(1): 87. CrossRef
Gastrointestinal Stromal Tumors Risk Stratification Utilizing Phospho-Histone H3 Evaluated by Manual Counting and Computer-Assisted Image Analysis
Cao Jin, Yan Huang, Mansoor Nasim, Yihe Yang, Lili Lee
International Journal of Surgical Pathology.2019; 27(7): 706. CrossRef
The utility of phosphohistone H3 in early prediction of benign and borderline phyllodes tumor recurrence
AymenM El-Saka, MohamedA Mlees, YomnaA Zamzam
Egyptian Journal of Pathology.2019; 39(2): 402. CrossRef
Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors
Min Jeong Kim, Mi Jung Kwon, Ho Suk Kang, Kyung Chan Choi, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hyoung-Chul Park
BioMed Research International.2018; 2018: 1. CrossRef
Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors
Piotr Lewitowicz, Jaroslaw Matykiewicz, Magdalena Chrapek, Dorota Koziel, Agata Horecka-Lewitowicz, Martyna Gluszek-Osuch, Iwona Wawrzycka, Stanisław Gluszek
Scanning.2018; 2018: 1. CrossRef
The mitosis‐specific marker phosphohistone‐H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study
Kin‐Long Chow, Ka‐Yu Tse, Ching‐Lung Cheung, Ka‐Wing Wong, Annie N Y Cheung, Richard W C Wong, Alice N H Chan, Nancy W F Yuen, Hextan Y S Ngan, Philip P C Ip
Histopathology.2017; 70(5): 746. CrossRef

Expression Patterns of Bcl-2 and PCNA in Cervical Intraepithelial Neoplasia.: Mee Sook Roh, Gi Yeung Huh, Sook Hee Hong; Korean J Pathol. 1995;29(6):703-713.

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Abstract PDF: Immunohistochemical stains for bcl-2 oncoprotein and PCNA and examination of the mitosis level were perfon-ned in 76 cases of cervical intraepithelial neoplasia (CIN). We studied the expression pattern of bcl-2 protein according to histologic grades and the function of bcl-2 oncogene associated with cellular proliferation by comparing with PCNA expression and the mitosis level. The results were as follows: 1) Of 76 cervical intraepithelial neoplasias, 23 (30.3%) were CIN I, 23 (30.3%) were CIN II, and 30 (39.4%) were CIN III. 2) Of 23 CIN I cases, grade 0 and 1 mitosis level were seen in 20 (87.0%), PCNA in 16 (69.6%), and bcl-2 in 19 (82.6%) cases, respectively, which indicates that CIN I lesions have a low cellular proliferative activity. 3) Of 30 CIN III cases, grade 2 and 3 mitosis level were noted in 28 (93.3%), PCNA in 25 (83.3%) and bcl-2 in 19 (63.3%) cases, respectively, which indicates that CIN III lesions have a high cellular proliferative activity. The results suggest that progressive increase of dysfunctional proliferative activity and abnormal decrease of cell death result in increased number of neoplastic cells according to CIN grade. Also the expression rate of bcl-2, PCNA and mitosis level were significantly different between CIN I and 111, which suggest that they might be good parameters for classifying CIN into low and high grade and for prediction of the biologic behavior of the CIN lesion.

Taxol-induced Pathological Findings in Rat Small Intestine.: Sun Hee Chang, Shi Nae Lee, Hee Soo Yoon, Min Sun Cho, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1997;31(12):1291-1296.

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Abstract PDF: Taxol is an active chemotherapeutic agent against a variety of solid tumors and a potentially useful drug for augmenting the cytotoxic action of radiotherapy against certain cancers. Taxol blocks cells in the mitotic phase of cell cycle. The aim of this study was to define the in vivo response of rapidly dividing cells of the small intestinal mucosa to taxol. We studied the numbers of apoptotic and mitotic cells and the expression of bcl-2 and p53 in rat jejunal crypt cells at 1, 2, 4, 8, 12, 16, and 24 hours and 3 and 5 days after intraperitoneal injection of taxol. Mitosis peaked at 2 and 4 hours and 12 and 16 hours. Apoptosis peaked at 16 hours and returned to normal after five days. The glands in crypts showed marked distortion with atypical lining cells after three days, which returned to normal at 5 days. bcl-2 expression was markedly decreased at 8 to 24 hours and subnormally recovered after three to five days. p53 showed no significant changes throughout. The histopathological changes in small intestine due to taxol were transient with complete recovery. bcl-2 expression was inversely corresponded to numbers of apoptosis. The changes were p53 independent. Further studies to understand the conditions that maximize the cell-cycle modulating effects of taxol cl-may greatly enhance its anti-tumor effectiveness.

A Study of the Correlation between Cellular Proliferating Activities and Prognosis in Gastrointestinal Stromal Tumors .: Hee Jin Chang, Duck Hwan Kim, Sung Sook Pang, Jin Hee Sohn, Jung Il Suh, In Sun Kim, Jong Sang Choi; Korean J Pathol. 1995;29(2):152-169.

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Abstract PDF: Gastrointestinal stromal tumors are notorious for their unpredictable clinical behavior. To assess the cellular proliferating activities, four different methods were used: mitotic count, nucleolar organizer region(AgNOR) staining, immunostaining of proliferating cell nuclear antigen (PCNA) and DNA ploidy were used on 39 cases of gastrointestinal stromal tumors. Additionally, we analysed cellularity, cellular atypism and necrosis. Among 39 cases of gastrointestinal stromal tumors, 11 cases were diagnosed as benign lesions according to clinicopathologic findings. Malignant lesions were arbitrarily classified into low grade(n=ll) and high grade(n=17) on the basis of absence or presence of recurrence, metastasis or tumor-related death during the follow-up period. Numbers of mitosis, AgNORs, PCNA index and DNA ploidy were correlated with grades of tumor and prognosis. Among them, AgNORs counting appeared to be the most useful in predicting prognosis. Numbers of mitosis, PCNA index and DNA ploidy showed varying degrees of overlap among the 3 groups. Among the histological parameters, cellular atypia showed some relationship with the prognosis that others did not reveal.

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