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Volume 56(2); March 2022
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Original Articles
Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy
Jongwon Lee, In-Seob Lee, Ji Yong Ahn, Young Soo Park, Jihun Kim
J Pathol Transl Med. 2022;56(2):63-72.   Published online November 16, 2021
DOI: https://doi.org/10.4132/jptm.2021.10.12
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AbstractAbstract PDFSupplementary Material
Background
Extremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution.
Methods
A total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed.
Results
Most cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies.
Conclusions
Awareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures.
Fatty acid synthetase expression in triple-negative breast cancer
Jin Hee Park, Hye Seung Han, So Dug Lim, Wook Youn Kim, Kyoung Sik Park, Young Bum Yoo, Seung Eun Lee, Wan-Seop Kim
J Pathol Transl Med. 2022;56(2):73-80.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.27
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  • 113 Download
  • 1 Citations
AbstractAbstract PDF
Background
Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.
Methods
Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN.
Results
FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.
Conclusions
We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.
Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury
Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae
J Pathol Transl Med. 2022;56(2):81-91.   Published online March 2, 2022
DOI: https://doi.org/10.4132/jptm.2021.12.27
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  • 1 Citations
AbstractAbstract PDF
Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.
Case Studies
An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing
Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon
J Pathol Transl Med. 2022;56(2):92-96.   Published online November 16, 2021
DOI: https://doi.org/10.4132/jptm.2021.10.15
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AbstractAbstract PDF
Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.
Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice
Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun
J Pathol Transl Med. 2022;56(2):97-102.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.28
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  • 111 Download
  • 1 Citations
AbstractAbstract PDF
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.
Recurrent malignant solitary fibrous tumor of the scalp: a case report and literature review
Ahmed Rabie, Abdulkarim Hasan, Yasein Mohammed, Ayman Abdelmaksoud, Ali A. Rabaan
J Pathol Transl Med. 2022;56(2):103-108.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.29
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  • 83 Download
AbstractAbstract PDF
Solitary fibrous tumor (SFT) is a rare type of mesenchymal neoplasm that first was discovered in the pleura but can also affect the peritoneum, lungs, mediastinum, and skin. Cutaneous malignant SFT is an extremely rare tumor that resembles dermatofibrosacoma protuberance (DFSP) histologically and immunohistochemically. Herein, we describe a case of malignant SFT that presented as a recurrent mass on the scalp. The first lesion was totally excised one year before recurrence and was diagnosed as a DFSP based on the histopathology and cluster of differentiation 34 immunostaining positivity. Re-examination of the previously examined specimen was considered. Activator of transcription 6 positivity was also detected in the tissue, confirming the diagnosis of a recurrent malignant SFT rather than DFSP. There was no evidence of recurrence, locoregional, or distant metastases at six months after lesion removal with a safety margin.
Letters to the Editor
And the story goes on: non-conventional dysplasia of the colorectum
Lavisha S. Punjabi, Yi Neng Lai, Anjula Thomas
J Pathol Transl Med. 2022;56(2):109-110.   Published online February 3, 2022
DOI: https://doi.org/10.4132/jptm.2021.12.29
  • 1,794 View
  • 39 Download
PDF
Renal cell carcinoma concomitant with multiple myeloma
Anubhav Narwal, Prashant Ramteke, Lalit Kumar, Saumyaranjan Mallick
J Pathol Transl Med. 2022;56(2):111-112.   Published online March 11, 2022
DOI: https://doi.org/10.4132/jptm.2022.01.21
  • 1,818 View
  • 38 Download
PDF
Newsletter
What’s new in molecular genetic pathology 2022: immune checkpoint inhibitor biomarkers and select solid tumors
Patricia C. Tsang, Guoli Chen
J Pathol Transl Med. 2022;56(2):113-114.   Published online March 11, 2022
DOI: https://doi.org/10.4132/jptm.2022.01.25
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  • 76 Download
AbstractAbstract PDF
Predictive biomarker testing plays a critical role in targeted immuno-oncology, including the use of immune checkpoint inhibitors (ICI) for various solid tumors. Molecular advancements in cancers of the breast, kidney and brain have continued to propel tumor classification and precision therapy.

JPTM : Journal of Pathology and Translational Medicine