Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.
Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.
The BRAF(V600E) mutation has been reported to occur in 30% to 80% of papillary thyroid carcinomas (PTCs). Although direct sequencing is the method most commonly used to identify mutations, this technique is not sensitive enough to accurately detect low level mutation. To determine the optimal diagnostic method for detecting the BRAF(V600E) mutation in PTC, we compared the diagnostic efficacy of four representative detection methods in formalin-fixed paraffin-embedded thyroid tissues obtained from 40 patients diagnosed with PTC. To detect the BRAF(V600E) mutation, we amplified exon 15 of the BRAF gene and performed mutational analysis with direct sequencing, denaturing high-performance liquid chromatography (DHPLC), pyrosequencing and colorimetric assay. The BRAF mutation was detected in 33 cases (82.5%) by DHPLC, 23 cases (57.5%) by direct sequencing, 22 cases (55.0%) by pyrosequencing, and 37 cases (92.5%) by colorimetric assay. The sensitivity, negative predictive value and accuracy of DHPLC were 100%. The specificity and positive predictive values for DHPLC, direct sequencing and pyrosequencing were 100%, and for colorimetric assay they were 14.3% and 83.8%, respectively. The kappa value for DHPLC was a perfect 1.0, which was superior to the other methods. In conclusion, DHPLC is a sensitive, specific and accurate method for detecting the BRAF(V600E) mutation, especially low level mutation, in PTC.
Background: The follicular variant of papillary thyroid carcinoma (FVPTC) presents distinct histologic subtypes and molecular genotyping. The preoperative diagnosis of FVPTC through fine-needle aspiration cytology (FNAC) is challenging. Methods: We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (n=30) and infiltrative FVPTC (n=29). Galectin-3 immunostaining and molecular analyses for BRAF and three RAS genes (NRAS, HRAS, and KRAS) were performed. Results: FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular neoplasm/suspicious for follicular neoplasm (14%), suspicious for PTC (29%), and PTC (34%). Galectin-3 immunostaining was positive in 50% of FNAC specimens. A BRAF mutation was found only in 14 (24%) tumors with the FNAC diagnosis of PTC or suspicious for PTC: 13 cases with the usual c.1799T>A (p.V600E) mutation and 1 case with a 3 base-pair deletion (c.1799_1801delTGA), resulting in a deletion of lysine at codon 601 and a deletion c.1799_1801delTGA that results in a valine-to-glutamate substitution at codon 600 (p.V600_K601>E) while preserving the reading frame. A BRAF K601E mutation was not found. RAS mutations were observed in 18 (33%) tumors (NRAS, 22%; HRAS, 6%; KRAS, 6%). Mutations of the three RAS genes were detected in codon 61 but not in codons 12 and 13. There was a decreasing trend of RAS mutation rates associated with an increasing risk of malignancy in the FNAC diagnostic categories. The triage efficacy of FNAC to make a recommendation for surgery was 73% for encapsulated tumors and 79% for infiltrative tumors. Addition of galectin-3 or the BRAF test to FNAC showed no significant improvement in the triage efficacy. However, RAS mutations significantly improved the triage efficacy of FNAC. There was no significant difference in the triage efficacy of FNAC, galectin-3 expression, and the prevalence of somatic mutations between encapsulated and infiltrative tumors. Conclusion: Thyroid FNAC has a low sensitivity for the detection of FVPTC regardless of histologic subtype. Encapsulated FVPTC and infiltrative FVPTC have similar molecular profiles and rates of galectin-3 expression. RAS mutational analysis is more useful than BRAF testing to improve the triage efficacy of FNAC for FVPTC.
Lipofibromatosis is a recently described rare benign fibrofatty tumor of childhood. It typically forms as an ill defined, slowly growing, painless mass. We present here the case of lipofibromatosis that occurred in a 21-year-old male who had complained of a bulging enlarged mass involving the right thigh and prepatella area for the previous 1 year. Magnetic resonance imaging showed an ill-defined reticular infiltration in the subcutaneous layer with subtle linear enhancement and high T2 signal intensity. The mass was surgically excised and it displayed an 11.0 x 5.5 x 1.5 cm-sized adipose appearance without encapsulation. Microscopically, the tumor was composed of alternating streaks of mature adipose tissue and a fibroblastic component that mainly involved the septa of adipose tissue. On immunohistochemical study, the fibroblastic component was positive for S-100, CD99, CD34, actin and bcl-2. He has shown an eventful recovery for 6 months after surgery.
목적: 이 연구의 목적은 유방암 위험 질환의 B 모드 초음파와 탄성 초음파 (sonoelastography) 소견을 알아 보고자 하였다. 대상과 방법: 2009년 4월부터 2010년 2월까지 1390예의 초음파 유도하 생검술이 시행되었다. 이 중 수술이나 1년 이상의 추적 영상검사가 시행된 순수한 경화성 선증 13예가 이 연구에 포함되었다. ...
Apocrine carcinoma arising from the apocrine sweat glands is a rare cutaneous malignant tumor which occurs predominantly in the axilla of elderly individuals. The typical histologic features of apocrine carcinoma is within a well developed glandular lumina with abundant eosinophilic cytoplasm and evidence of decapitation secretion. In rare instances, predominant signet ring cell features in apocrine carcinoma has been reported. We experienced a case that occured in the right axilla of a 59-year-old. Histopathologic examination showed a solid tumor that extended from the upper dermis into the subcutis, with a delicate infiltrate of epithelial cells. The cells had granular amphophilic cytoplasm, predominantly showed distinct signet ring cell morphology, and were strongly positive for epithelial mucin. Both lysozyme and gross cystic disease fluid protein-15 were identified in the tumor cells. We diagnosed this to be a case of primary signet ring cell apocrine carcinoma of the axilla after several immunohistochemical and clinical evaluations.
Background: The grey zone of cervical cytology, and in particular atypical squamous cells, cannot exclude HSIL (ASC-H) causes diagnostic difficulties and increases medical expenses. We analyzed p16(INK4a) expression in ASC-H liquid-based cytology specimens (LBCS) to develop more effective methods for the management of ASC-H patients. Methods: We carried out p16(INK4a) immunostaining with 57 LBCS of ASC-H diagnostic categories, all of which were histologically cofirmed and 43 cases of which were compared with the results of a human papillomavirus (HPV) chip test. Results: p16(INK4a) immunostaining with ASC-H LBCS was positive in 20% (3/15) of cervicitis, 25.0% (3/12) of tissue-low-grade squamous intraepithelial lesion, 75.0% (18/24) of tissue-high grade squamous intraepithelial lesion (HSIL), and 100% (6/6) of invasive cancer cases. The positivity of p16(INK4a) in LBCS was correlated with higher grade of histologic diagnosis (r=0.578, p=0.000). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16(INK4a) immunostaining for the prediction of tissue-HSIL+ were 80.0%, 77.8%, 80.0%, and 77.8%, respectively. The sensitivity, specificity, PPV, and NPV of p16(INK4a) immunostaining plus HPV chip test for predicting tissue-HSIL+ were 71.2%, 86.4%, 84.2%, and 79.2%. Conclusions: p16(INK4a) immunostaining as well as HPV chip testing with remaining LBCS with ASC-H are useful objective markers for the prediction of tissue-HSIL+.
Although thyroid transcription factor-1 (TTF-1) immunoreactivity is considered as a specific marker of lung and thyroid neoplasms, it may be positive in a proportion of extrapulmonary adenocarcinomas. This study examined the expression of TTF-1 in 555 colorectal adenocarcinomas using three commercial monoclonal antibodies: clone SPT24 (Novocastra) and 8G7G3/1 (Dako and Cell Marque), and compared the TTF-1 staining with other immunohistochemical markers, cytokeratin (CK) 7, CK 20, caudal-type homeobox transcription factor 2 (CDX2), and MUC2. The clinicopathological prognostic factors were compared with the TTF-1 expression status. Nuclear TTF-1 staining was detected in 24 cases (4.3%) with the SPT24 antibody and 18 cases (3.2%) with the 8G7G3/1 antibody. All cases positive for 8G7G3/1 were also positive for SPT24. CDX2 was expressed constantly in all 24 TTF-1-positive colorectal cancers, whereas CK7, CK20, and MUC2 were detected in 2 (8.3%), 23 (95.8%), and 8 (33.3%) cases, respectively. There was no correlation between TTF-1 expression and clinicopathological significance. To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histological features, and the results of other markers, such as CK7, CK20, and CDX2. MUC2 can be used as supplementary information to confirm difficult cases.
Purpose: We want to validate the use of the silver-enhanced in situ hybridization (SISH) technique as comparised with fluorescence in situ hybridization (FISH) technique for assessing the HER2 gene amplification of breast carcinoma. Methods: Tissue microarray (TMA) blocks from 58 breast cancer specimens were prepared and the concordance between HER2 gene amplification in breast cancer was determined by the FISH (PathVysion (R), Abbot/Vysis) technique and the automated silver in situ hybridization (SISH, INFORM (TM), Ventana) technique. For comparison, all the specimens were stained by immunohistochemistry (Ventana-PATHWAY (R) 4B5). Evaluation was performed by two pathologists and with following the instructions of the manufacturers and the guidelines of the American Society of Clinical Oncology/College of American Pathologists. Results: The results of SISH and FISH were identical in all 58 cases; 17 cases showed HER2 amplification, and on the other hand, 41 cases didn't show HER2 amplification. Five weakly positive (2+) cases in immunohistochemistry staining revealed one HER2 amplification and four no HER2 amplification on both SISH and FISH. The SISH results of the HER2/CEP17 ratio were well correlated with the FISH results of the HER2/CEP17 ratio (correlation coefficient r=0.745, Linear regression r(2)=0.555, p<0.001). Conclusion: The results of the SISH technique for assessing the HER2 status of excised breast carcinoma is comparable to the result obtained by FISH. However, SISH has the advantage of having permanent end result that can be visualized by an ordinary light microscope and less laborious preparation and time is needed than is required by FISH. SISH seems to be more feasible than FISH for assessing HER2 amplification of breast cancer.
Colorectal adenocarcinoma with rhabdoid features is extremely rare and only three cases have been previously reported. We report a 62-year-old man who presented with general weakness and poor oral intake for 6 months, and showed multiple masses at the duodenum, jejunum, ileum and the ascending colon. The patient underwent right hemicolectomy with small bowel segmental resection. Microscopically, the tumor masses were characterized by incohesive sheet of neoplastic cells with vesicular nuclei, large nucleoli, and abundant eosinophilic cytoplasm. Immunohistochemical studies showed strong reactivity of the tumor cells for pan-cytokeratin, anti-endomysial antibodies (EMA) and vimentin. This was a case of undifferentiated carcinoma with prominent rhabdoid feautures arising in the ascending colon with multiple gastrointestinal metastases.