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Volume 53(3); May 2019
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Reviews
Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group
Dong Hoon Shin, Hyo Sup Shim, Tae Jung Kim, Heae Surng Park, Yun La Choi, Wan Seop Kim, Lucia Kim, Sun Hee Chang, Joon Seon Song, Hyo jin Kim, Jung Ho Han, Chang Hun Lee, Geon Kook Lee, Se Jin Jang
J Pathol Transl Med. 2019;53(3):153-158.   Published online February 28, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.22
  • 5,305 View
  • 231 Download
  • 4 Citations
AbstractAbstract PDF
Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Primary Age-Related Tauopathy: An Elderly Brain Pathology Frequently Encountered during Autopsy
Daru Kim, Hyung-Seok Kim, Seong-Min Choi, Byeong C. Kim, Min-Cheol Lee, Kyung-Hwa Lee, Jae-Hyuk Lee
J Pathol Transl Med. 2019;53(3):159-163.   Published online March 19, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.14
  • 4,920 View
  • 176 Download
  • 15 Citations
AbstractAbstract PDF
Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.
Original Articles
Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma
Amany Salama, Mohammad Arafa, Eman ElZahaf, Abdelhadi Mohamed Shebl, Azmy Abd El-Hameed Awad, Sylvia A. Ashamallah, Reda Hemida, Anas Gamal, Abd AlRahman Foda, Khaled Zalata, El-Said M. Abdel-Hady
J Pathol Transl Med. 2019;53(3):164-172.   Published online February 28, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.12
  • 6,071 View
  • 287 Download
  • 3 Citations
AbstractAbstract PDF
Background
In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC.
Methods
We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis.
Results
The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012).
Conclusions
The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.
Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis
Jung-Soo Pyo, Nae Yu Kim, Won Jin Cho
J Pathol Transl Med. 2019;53(3):173-179.   Published online March 5, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.03
  • 4,830 View
  • 145 Download
  • 4 Citations
AbstractAbstract PDF
Background
Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin- 1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis.
Methods
The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted.
Results
Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS.
Conclusions
Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice.
Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer
Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee
J Pathol Transl Med. 2019;53(3):180-187.   Published online March 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.08
  • 5,174 View
  • 178 Download
  • 10 Citations
AbstractAbstract PDF
Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.
Case Studies
A Rare Case of Adenosquamous Carcinoma Arising in the Background of IgG4-Related Lung Disease
Sangjoon Choi, Sujin Park, Man Pyo Chung, Tae Sung Kim, Jong Ho Cho, Joungho Han
J Pathol Transl Med. 2019;53(3):188-191.   Published online March 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.21
  • 4,168 View
  • 146 Download
  • 8 Citations
AbstractAbstract PDF
IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.
Frozen Cytology of Meningeal Malignant Solitary Fibrous Tumor/Hemangiopericytoma
Myunghee Kang, Na Rae Kim, Dong Hae Chung, Gie-Taek Yie
J Pathol Transl Med. 2019;53(3):192-197.   Published online April 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.20
  • 4,320 View
  • 131 Download
  • 4 Citations
AbstractAbstract PDF
A 51-year-old woman presented with severe dizziness. The brain magnetic resonance image revealed a 5.5 cm multiloculated mass with a thick rim in the left temporal lobe. Cytological examination of frozen diagnosis of the mass showed hypercellular sheets of round and rhabdoid cells in a hemorrhagic background, and two mitotic figures were observed. Histologically, the excised dura-based mass consisted of predominantly round cells with small foci of rhabdoid tumor cells in a pseudoalveolar pattern in a hemorrhagic background, and the cells showed nuclear positivity for signal transducer and activator of transcription 6 as well as frequent mitosis. The mass was diagnosed as a grade 3 solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). The cytological diagnosis of SFT/HPC is challenging because of the heterogeneous cytological findings, such as histological heterogeneity, and because there are no standardized cytological criteria for malignant SFT/HPC. Cytological findings, such as singly scattered small cells, hypercellularity, rare ropy collagen, and round and rhabdoid cells with pseudoalveolar pattern, may assist in the diagnosis of malignant SFT/HPC.

JPTM : Journal of Pathology and Translational Medicine