Deep Learning for the Pathologic Diagnosis of Hepatocellular Carcinoma, Cholangiocarcinoma, and Metastatic Colorectal Cancer.

Diagnosing primary liver cancers, particularly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), is a challenging and labor-intensive process, even for experts, and secondary liver cancers further complicate the diagnosis. Artificial intelligence (AI) offers promising solutions to these diagnostic challenges by facilitating the histopathological classification of tumors using digital whole slide images (WSIs). This study aimed to develop a deep learning model for distinguishing HCC, CC, and metastatic colorectal cancer (mCRC) using histopathological images and to discuss its clinical implications. The WSIs from HCC, CC, and mCRC were used to train the classifiers. For normal/tumor classification, the areas under the curve (AUCs) were 0.989, 0.988, and 0.991 for HCC, CC, and mCRC, respectively. Using proper tumor tissues, the HCC/other cancer type classifier was trained to effectively distinguish HCC from CC and mCRC, with a concatenated AUC of 0.998. Subsequently, the CC/mCRC classifier differentiated CC from mCRC with a concatenated AUC of 0.995. However, testing on an external dataset revealed that the HCC/other cancer type classifier underperformed with an AUC of 0.745. After combining the original training datasets with external datasets and retraining, the classification drastically improved, all achieving AUCs of 1.000. Although these results are promising and offer crucial insights into liver cancer, further research is required for model refinement and validation.

Intrathyroidal metastasis of tonsillar squamous cell carcinoma masquerading as a primary thyroid tumor.

Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography-computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus-positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.

Metallic implant-associated lymphoma: ALK-negative anaplastic large cell lymphoma associated with total knee replacement arthroplasty.

Metallic implant-associated lymphomas are extremely rare. Only seven cases have been reported in association with knee joint arthroplasty, and all tumors were large B-cell lymphomas. This report is the first case of anaplastic large cell lymphoma occurring after total knee replacement arthroplasty. An 80­year­old female patient was admitted because of right knee pain for 2 years. She had undergone total knee replacement arthroplasty 10 years prior. Computed tomography showed an irregular osteolytic lesion in the right lateral femoral condyle, adjacent to the metallic prosthesis. Histologic findings reveal sheets of anaplastic tumor cells that were positive for CD2, CD4, CD5, CD43, and CD30 but negative for CD3, CD20, CD15, and anaplastic lymphoma kinase. Epstein-Barr encoding region in situ hybridization was negative. Analysis of T-cell receptor γ gene rearrangement studies using BIOMED-2-based multiplex polymerase chain reaction confirmed monoclonal T cell proliferation. The woman was finally diagnosed with ALK-negative anaplastic large cell lymphoma.

Molecular subtypes of triple-negative breast cancer: understanding of subtype categories and clinical implication.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous entity that encompasses several subtypes with distinct molecular characteristics. The patients with TNBCs show unpredictable response to the chemotherapy, and further there is the lack of effective agents. Thus, many studies have been underway to discover targeted therapy suitable for patients with specific genetic alterations in each molecular subtypes. TNBCs are classified as four major molecular subtypes according to the gene expression patterns. These are luminal androgen receptor (LAR), mesenchymal-like, immunomodulatory (IM), and basal-like types. CONCLUSION: Here, we discuss the unique molecular features of each subtype as well as promising targets for anti-cancer therapy.

Topographical Anatomy of the Distal Ulna Attachment of the Radioulnar Ligament.

PURPOSE: The deep component of the distal radioulnar ligament provides translational stability and rotational guidance to the forearm. However, controversy exists regarding the importance of this structure as well as the nature of its attachment to the distal ulna. We aimed to evaluate the topographic anatomy of the distal ulna attachment of both the superficial and the deep components of the radioulnar ligament and to assess the relationship between its internal and its external morphometry. METHODS: Thirteen human distal ulnae attached by ulnar part of the distal radioulnar ligament were scanned using micro-computed tomography and reconstructed in 3 dimensions. In addition, the distal radioulnar ligaments were examined under polarized light microscopy to determine the histological characteristics of collagen contained within the ligaments. RESULTS: The deep limbs have broad marginal insertions at the fovea, whereas the superficial limbs have a circular and condensed insertion to the ulnar styloid. The center of the deep limb was separated from the base of the ulnar styloid by a mean of 2.0 ± 0.76 mm, and this distance was positively correlated with the width of the ulnar styloid. The mean distance between the center of the ulnar head and the center of the fovea was 2.4 ± 0.58 mm. The proportion of collagen type I was lower in the deep limb than in the superficial limb. CONCLUSIONS: This new observation of the footprint of the radioulnar ligament in the distal ulna indicates that the deep limb may serve as an internal capsular ligament of the distal radioulnar joint, whereas the superficial limb as the external ligament. CLINICAL RELEVANCE: Knowledge of the topographic anatomy of the radioulnar ligament's attachment to the distal ulna may provide a better understanding of distal radioulnar ligament-related pathologies.

Expression pattern of programmed death-1 in lymphocyte-rich classical Hodgkin lymphoma according to the growth patterns.

We present a rare case of lymphocyte-rich classical Hodgkin lymphoma (LRCHL), which exhibited different expression patterns of programmed death-1 (PD-1) in nodular and interfollicular areas. A 57-year-old male patient presented with neck masses. Neck computed tomography showed enlargement of multiple lymph nodes in right Level II and III. Histologic examination of the excised lymph node revealed LRCHL with nodular and interfollicular patterns. Immunohistochemical analysis for PD-1 revealed a small number of weakly stained cells in the interfollicular area. PD-1 (+) cells were markedly increased in cell number and staining intensity in the nodular area and formed rosettes around the tumor cells.

Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

Smad1 expression in follicular lymphoma.

BACKGROUND: Follicular lymphomas present with various immunohistologic patterns. The immunohistochemical markers used in the diagnosis of follicular lymphoma show variable degrees of sensitivity and specificity, and thus, additional germinal center markers are required. Smad1 has been reported to be overexpressed in follicular lymphoma, but little is known regarding the expression patterns of Smad proteins in human lymphoid tissue. METHODS: In the present study, we performed immunohistochemistry for traditional germinal center markers and for Smad1 in human reactive lymphoid and follicular lymphoma tissues to investigate Smad1's usefulness in the diagnosis of follicular lymphoma. RESULTS: In the reactive germinal centers, most cells were positive for Smad1. Among the 27 follicular lymphoma cases, 17 of 21 (80%) were Smad1 positive, 17 of 27 (63%) were positive for CD10, and 23 of 27 (85%) were positive for Bcl6. Notably, three cases expressed CD10 only, and one only expressed Bcl6. All these cases were grade 3 tumors and showed follicular and diffuse growth patterns. CONCLUSIONS: These results indicate that Smad1 is a candidate as a germinal center marker. Furthermore, they suggest that the Smad signaling pathway might be involved in follicular lymphoma.

Anatomical confirmation of computed tomography-based diagnosis of the atherosclerosis discovered in 17th century Korean mummy.

In the present study on a newly discovered 17th century Korean mummy, computed tomography (CT) revealed multiple aortic calcifications within the aortic wall that were indicative of ancient atherosclerosis. The CT-based findings were confirmed by our subsequent post-factum dissection, which exhibited possible signs of the disease including ulcerated plaques, ruptured hemorrhages, and intimal thickening where the necrotic core was covered by the fibrous cap. These findings are strong indicators that the mummy suffered from aortic atherosclerosis during her lifetime. The present study is a good example of how CT images of vascular calcifications can be a useful diagnostic tool in forming at least preliminary diagnoses of ancient atherosclerosis.

Restoration of the central slip in congenital form of boutonniere deformity: case report.

We present a case of a congenital form of a boutonniere deformity involving both little fingers with a poorly differentiated extensor mechanism and the absence of the tendinous attachment on the dorsal aspect of the middle phalanx. This complex deformity was evaluated histologically followed by successful reconstruction of the central slip.

Cystic benign phyllodes tumor in the inguinal region.

The present lesion was the first reported case of a benign intracystic phyllodes tumor in the inguinal region. We report the case of a 51-year-old female patient who presented with an inguinal mass. A clinical diagnosis of malignant lymphoma was considered in this case. The resected tumor was well-circumscribed and showed numerous papillary nodular protrusions into a central cystic cavity (3.5×2.5 cm). The microscopic findings showed hyperplastic epithelium-lined cysts with leaf-like intraluminal epithelium-lined bland stromal projections. The epithelial cell linings were strongly positive for estrogen and progesterone receptors.

Collision of adenocarcinoma and schwannoma of the stomach: a case report.

The simultaneous occurrence of an adenocarcinoma and schwannoma is extremely rare in the stomach, and only one such case has been previously reported, which presented as two separate masses. Indeed, the collision of these tumors has never been reported. We report the case of a 61-year-old male patient who was diagnosed with the synchronous development of a schwannoma and advanced mucinous adenocarcinoma of the stomach, in which the carcinoma cells focally invaded the schwannoma.

Atypical epidermoid cyst in renal pelvis and histogenetic implications.

Since the renal epidermoid cyst is too rare, the mechanisms of squamous morphogenesis have not well characterized. A 73-year-old female was referred with an incidentally detected renal pelvis mass. Abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis. Total nephroureterectomy was performed under the impression of a renal pelvis malignancy. The patient was discharged without postoperative complication. The outer surface of mass lesion was lined with urothelia and squamous epithelia, containing keratinous materials. The urothelia were positively stained against uroplakin II and cytokeratin 7, whereas almost of the squamous epithelia were negative with uroplakin II. The two different epithelia were generally sharply demarcated. Interestingly, some part of squamous epithelia contained uroplakin-positive and many more cytokeratin 7-positive cells. The atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before, and the unique immunohistochemical results may understand the histogenetic implications of the lesion.

Extraintestinal migration of Centrorhynchus sp. (Acanthocephala: Centrorhynchidae) in experimentally infected rats.

Reptiles were known to serve as paratenic hosts for Centrorhynchus (Acanthocephala: Centrorhynchidae) in Korea, but the infection course in experimental animals was not elucidated yet. In this study, the tiger keelback snakes (Rhabdophis tigrinus) were collected and digested with artificial pepsin solution, and the larvae of Centrorhynchus were recovered from them. Then, the collected larvae were orally infected to rats for developmental observations. In rats, all the larvae were observed outside the intestine on day 3 post-infection (PI), including the mesentery and abdominal muscles. As for the development in rats, the ovary of Centrorhynchus sp. was observed at day 15 PI, and the cement glands were 3 in number. Based on the morphological characteristics, including the arrangement of proboscis hooks, these larvae proved to be a species of Centrorhynchus, and more studies were needed for species identification.

A nasal myiasis in a 76-year-old female in Korea.

On July 2009, 5 fly larvae were discovered inside the nose of a 76-year-old female. She was living in Cheonan-si, and in a state of coma due to rupture of an aortic aneurysm. Surgery was performed on the day of admission, and the larvae were found 4 days later. By observing their posterior spiracle, the larvae were identified as Lucilia sericata. Considering the rapid development of this species, the infection was likely acquired during hospitalization. Further investigation on the hospital environment should be needed to know the origin of the infection.

A spindle cell predominant pancreatic solid-pseudopapillary tumor.

A hitherto unrecognized variant of solid-pseudopapillary tumor (SPT) of the pancreas is reported. The tumor presented in the pancreatic tail of a 44-year-old female patient. It was a well-defined, solid nodule measuring 25 mm in diameter, with homogenous tan gray cut surface. Histologically, the neoplasm was mostly composed of sheets of spindle cells. No cellular atypia and mitosis was identified. The periphery of the tumor showed typical feature of SPT. Immunohistochemically, the tumor cells were positive for vimentin, CD10, CD56, beta-catenin, and alpha1-antichymotrypsin, but negative for cytokeratin, chromogranin, synaptophysin and S-100 protein. Ultrastructurally, the tumor showed a few acinar spaces with microvilli between tumor cells. This case is peculiar in that the tumor did not show gross cystic change and predominantly consists of spindle shaped tumor cells, so may cause difficult diagnostic problem.