Familial Adenomatous Polyposis (FAP) is a multi-tumoral syndrome that includes neoplasms in the duodenum, brain, pancreas and thyroid. The Cribriform Morular Variant (CMV) is a rare form of Papillary Thyroid Cancer seen in patients with FAP. Presented here is a 32 year old female who initially presented with an anterior neck mass followed years later by a rectal mass. She was diagnosed with FAP and colorectal adenocarcinoma and underwent total proctocolectomy with end ileostomy. She subsequently underwent a total thyroidectomy which revealed CMV Papillary Thyroid Carcinoma (CMV-PTC). Since FAP can have diverse presentations, a high index of suspicion is needed in order to make an earlier diagnosis to reduce potential morbidity and mortality. Papillary thyroid carcinoma can predate colonic polyposis. Identifying CMV-PTC early on can serve as an opportunity diagnose FAP early.

A 61-year-old woman presented with a 2-month history of non-painful left eye proptosis. Imaging studies showed a superotemporal mass in the left orbit with intracranial extension. Surgical excision of the orbitocranial mass was performed and histopathologic examination revealed metastatic papillary thyroid carcinoma. She subsequently underwent total thyroidectomy. Orbital metastasis from thyroid carcinoma is rare and can be the initial manifestation of occult disease in 63% of cases.

OBJECTIVE

The aim of this study was to determine the upgrade rate in diagnosis of biopsy-proven papillary breast lesions on core needle biopsy and their respective surgical excisions, and to assess for predictive factors associated with an upgrade at St. Luke’s Medical Center – Global City.

A retrospective review of our institution’s database identified 184 papillary breast lesions diagnosed by core needle biopsy. The study population consisted of 71 samples that met the inclusion criteria. The overall upgrade and concordance rates were determined and analyzed if there was any significant association with clinical demographics, radiologic findings, and core diameter on gross examination. Continuous variables were presented as mean and median, and Shapiro-Wilk test was used to assess normality of data. Categorical variables were expressed as frequencies and percentages. Simple logistic regression analysis with Firth’s bias correction was performed to determine the variables associated with a diagnostic upgrade. P values ≤0.05 were considered statistically significant.

A total 71 patients, all female, were included in the study. The overall upgrade rate was 8.45% (95% CI: 3.16-17.49%) in comparison with the diagnosis of the initial CNB and SE alone. This translated to 6/71 samples in this study. The overall concordance was 91.55% based on clinical significance, and an individual diagnosis concordance rate of 78.87%. None of the predictive factors (i.e., age, history of breast cancer, BI-RADS score, and gross core diameter) assessed showed an association with a diagnostic upgrade.

The computed overall upgrade rate is within range of currently published literature. The concordance rates for both clinical significance and individual diagnosis were quite high, suggesting good reproducibility of histopathologic diagnosis within our institution. This was also found to be consistent with other studies. Of the predictive factors, none showed an association to a diagnostic upgrade. Despite the latter, our findings may be of value within the medical center in further exploring and expanding the data set at hand, such that it may hopefully contribute to local guidelines in managing PBLs in the future.

OBJECTIVE: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC). METHODS: Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. RESULTS: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. CONCLUSIONS This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.
Humans ; Leukocytes, Mononuclear ; Head and Neck Neoplasms/drug therapy* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immunotherapy ; Prognosis

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac⁴C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac⁴C modification sites, thereby providing a potent sequencing tool for tRNA-ac⁴C research. Our findings expand the repertoire of tRNA ac⁴C modifications and identify a role of tRNA ac⁴C in the regulation of mRNA translation in HNSCC.
Humans ; DNA-Binding Proteins ; Head and Neck Neoplasms/genetics* ; N-Terminal Acetyltransferases ; RNA, Transfer ; Serine ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Squamous cell carcinoma (SCC) of the kidney is a rare malignancy and has a poor prognosis because it is usually detected and presents at an advanced stage of the disease. Due to lack of studies regarding its clinical course and its radiologic features, it is usually not detected and presents as an incidental finding in histopathologic results. This type of malignancy more often is related to Renal stones secondary to chronic infection, inflammation, and irritation. A 52-year-old Filipino woman was referred to this institution due to flank pain and constant weight loss. The authors administered antibiotics then performed simple nephrectomy on her. A pathologic examination revealed Squamous Cell Carcinoma with Sarcomatoid differentiation. Four months after the operation, patient was readmitted due to lowback pain and generalized weakness which led to a suspicion of a possibility of Bone Metastasis. Patient was offered further workups such as whole abdominal CT scan with contrast and other palliative treatments however she refused and opted to be discharged despite medical advice. Patient then died 2 weeks after being home against medical advice.
Carcinoma, Squamous Cell ; Staghorn Calculi

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by sensitivity to sunlight and predisposition to cutaneous malignancies. There are various types, including the Variant type, which does not manifest with acute sunburn reactions. This results to the development of multiple malignancies that are often discovered at late stages, making management more challenging. This is a case of a 54-year-old Filipino female presenting with multiple basal cell carcinomas (BCCs) on several areas of the face and advanced cutaneous squamous cell carcinoma (cSCC) on the right zygomatic area, treated with imiquimod 5% cream and external beam radiation therapy, respectively. There was an excellent response of the BCCs to imiquimod 5% cream and good tumoral response of the SCC to radiation therapy, with tolerable side effects, highlighting the use of these palliative treatment modalities for XP patients with multiple, unresectable, or difficult-to-treat cutaneous malignancies.

We report a case of an uncommonly aggressive presentation of the rare entity of synchronous papillary (PTC) and follicular thyroid carcinomas (FTC) in a 67-year-old woman initially presenting with thyrotoxicosis from Graves’ disease. She was found to have two thyroid nodules with extensive intra-cardiac tumour thrombus, symptomatic left pelvis bony metastasis with pathological fracture, pulmonary metastases and mediastinal lymph node metastases. Further investigations suggested a diagnosis of synchronous papillary and metastatic follicular thyroid cancer. Treatment with radical surgery followed by adjuvant therapeutic radioiodine ablation was proposed, but the patient declined all forms of cancer-specific therapy and was elected solely for a palliative approach to treatment. We discuss the diagnostic considerations in arriving at the diagnosis of synchronous thyroid malignancy – in this case the clear features of PTC and the strong probability of FTC due to invasiveness and metastatic follicular lesions. This case underscores potential limitations of the ACR TI-RADS system, notably with certain ultrasonographic features suggesting malignancy that might not be adequately captured. Notably, the aggressive presentation of DTC in this case may be contributed by the concurrent presence of Graves’ Disease, suggesting heightened vigilance when assessing potential thyroid malignancies in such patients.
Papillary Thyroid Carcinoma ; Thyroid Cancer, Papillary ; Follicular Thyroid Carcinoma ; Adenocarcinoma, Follicular ; Graves Disease