Malignant Entities Research Articles

In silico annotation of follicular thyroid neoplasm associated metabolic pathways and involved biomarkers: An aid to diagnosis

The follicular thyroid neoplasm (FTN) is like an unsolved puzzle at some stage in preoperative diagnosis. Usually, for preliminary characterization of thyroid lesions, clinicians depend much on fine-needle aspiration cytology (FNAC). However, in the case of FTN, FNAC cannot distinguish between benign and malignant entities, as both are exhibiting predominant follicular architecture. Cytological/ architectural/ or cellular criteria alone is not enough to differentiate Follicular adenoma (FA), Follicular thyroid carcinoma (FTC), Follicular variant of papillary thyroid carcinoma (FVPTC) together with Non-Invasive Follicular variant of Papillary Thyroid Carcinoma (NIFTP), Encapsulated FVPTC (EFVPTC) and well-differentiated neoplasm of uncertain malignant potential. Thus, the genetic analysis can be used as a novel diagnostic approach that should be applied with the traditional method for easy diagnosis of follicular thyroid neoplasm, which reduces the risk of unnecessary surgeries. This present study tried to explore the current genetic assessment of FTN through review of the genetics of FTN studied from 2009 to 2019 which showed the characterization of differential gene expression in these follicular neoplasms some extent. Also, pathway analysis has potentially implemented to minimize the diagnosis dilemma. In addition to the previously identified pathways and associated target genes, some novel endocrine cancer-related pathways with putative target genes of FTN have been remoted from characterizing tumor with follicular pattern. The observed genes might be considered as diagnostic biomarker in the respective FTN associated metabolic pathways.

N-linked α2,6-sialylation of integrin β1 by the sialyltransferase ST6Gal1 promotes cell proliferation and stemness in gestational trophoblastic disease

IntroductionGestational trophoblastic disease (GTD) encompasses a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue, including partial hydatidiform mole, complete hydatidiform mole and choriocarcinoma. β-galactoside α2,6 sialyltransferase 1 (ST6Gal1), the primary sialyltransferase responsible for the addition of α2,6 sialic acids, is strongly associated with the occurrence and development of several tumor types. However, the role of ST6Gal1/α2,6 -sialylation of trophoblast cells in GTD is still not well understood. MethodsThe expression of ST6Gal1 was investigated in GTD and human immortalized trophoblastic HTR-8/SVneo cells and human gestational choriocarcinoma JAR cells. We evaluated the effect of ST6Gal1 on proliferation and stemness of trophoblastic cells. We also examined the effect of internal miR-199a-5p on ST6Gal1 expression. The role of ST6Gal1 in regulating α2,6-sialylated integrin β1 and its significance in the activation of integrin β1/focal adhesion kinase (FAK) signaling pathway were also explored. ResultsST6Gal1 was observed to be highly expressed in GTD. Overexpression of ST6Gal1 promoted the proliferation and stemness of HTR-8/SVneo cells, whereas knockdown of ST6Gal1 suppressed the viability and stemness of JAR cells. MiR-199a-5p targeted and inhibited the expression of ST6Gal1 in trophoblastic cells. In addition, we revealed integrin β1 was highly α2,6-sialylated in JAR cells. Inhibition of ST6Gal1 reduced α2,6-sialylation on integrin β1 and suppressed the integrin β1/FAK pathway in JAR cells, thereby affecting its biological functions. DiscussionThis study demonstrated that ST6Gal1 plays important roles in promoting proliferation and stemness through the integrin β1 signaling pathway in GTD. Therefore, ST6Gal1 may have a potential role in the occurrence and development of GTD.

Multiple and hereditary renal tumors: a review for radiologists

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2–4% of "sporadic" multifocality and 5–8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended.Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition.The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

Role of Uterine Artery Ligation and Chemotherapy in Atypical Cases of Gestational Trophoblastic Disease: A Case Report of Atypical GTD Diagnosis & Management

Introduction Gestational trophoblastic disease[1 i ] is a rare developmental form of proliferative trophoblastic tissue in women of reproductive age that involves both benign and malignant entities that include hydatidiform mole (complete or partial), choriocarcinoma, invasive mole, epithelioid trophoblastic tumor (ETT), and placental site trophoblastic tumor (PSTT). Four of these known as gestational trophoblastic neoplasia [2 ii], and hydatidiform is most common type of GTD. Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease that is almost always malignant, and can metastasize and be fatal if not treated. The ultimate treatment for GTD includes surgery (evacuation of the proliferative trophoblastic tissue, hysterectomy), chemotherapy regimens, radiotherapy and emerging targeted therapies. It is one of the most chemotherapy responsive and highly curable cancer. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a case of atypical GTD {uncommon, that is not fitting a single diagnosis} treated by chemotherapy and bilateral uterine artery ligation.

Male’s Primary Breast Lymphoma: Rare Entity of Breast Malignancy, Wad Madani Teaching Hospital, Gezira State, Sudan, August 2023

<i>Background</i>: Primary breast lymphoma is a malignant lymphoma primarily involving breast in absence of previously detected lymphoma localizations. <i>Method</i>: A male of forty years old admitted to Department of Surgery; Wad Madani Teaching Hospital; Gezira State; Sudan; complaining of left breast lump for three months. Condition observed as a painful swelling in left breast, increasing gradually in size, associated with continuous high-grade fever, no rigors and relieved by analgesia, no nipple discharges. Had significant weight loss, anorexia, fatigability, back pain, dry cough with no hemoptysis, no history of headache, and no past or family history of similar condition. Examination: patient looks ill, pale, and not jaundiced. Breast examination: Left breast was larger than right one. Left breast: no nipple destruction, nipple was directed downward medially, no skin changes or dimpling, and no ulceration. There was a mass in left upper outer quadrant, measuring 6*7 cm, smooth surface, hard in consistency with well-defined edges, and attached to muscles but not to skin. No palpable axillary lymph nodes. Right breast was normal. Chest and abdominal examination were unremarkable. Investigations: Fine needle aspiration cytology showed poorly differentiated carcinoma. Incisional biopsy revealed: high grade Non-Hodgkins Lymphomas (Diffuse Large B Cell Lymphoma). He was referred to oncological department for neoadjuvant chemoradiotherapy. Conclusion and <i>Recommendation</i>: Primarily breast lymphoma is extremely rare among male, showing features mimicking breast carcinoma. Incisional biopsy was recommended for investigation of breast lump especially among males.

Ovarian Germ Cell Tumors in North-Western India: A Comprehensive 3-Year Retrospective Study of 145 Cases at a Tertiary Cancer Hospital.

Germ cell tumors encompass a broad spectrum of neoplasms arising from germ cell lineage, demonstrating varying histological profiles and clinical presentations. These tumors encompass a range of benign and malignant entities. While global trends provide insights into their prevalence, specific regional variations, such as those within North-Western India, remain less explored. This study seeks to bridge this knowledge gap by examining the prevalence and characteristics of germ cell tumors within a tertiary cancer hospital. In this retrospective analysis, all cases of germ cell tumors diagnosed over a 3-year period in the specified tertiary cancer hospital were included. Cases with incomplete records or inadequate pathological data were excluded. Data encompassing histological subtypes, patient age distribution, clinical presentations, and histopathological features were collected and analyzed. The study comprised 145 cases of germ cell tumors. Teratomas were the most prevalent subtype, with mature teratomas accounting for the majority. The highest incidence occurred within the 21-30-year age group with a mean age of 24.77years. Abdominal mass (56%) and abdominal pain (34%) were the prominent clinical presentations. Benign cases constituted the majority 85.5%. Solid tumors (p < 0.00001) and tumors more than 10cm (p .029028) were found to have a high propensity to be malignant, which was proven to be statistically significant. This study comprehensively explains germ cell tumors' prevalence, clinical features, and histopathological subtypes in a tertiary cancer hospital in North-Western India. The predominance of teratomas, particularly mature ones, aligns with global trends. The age distribution and clinical presentations reflect common patterns. The diverse histopathological appearances underscore the heterogeneous nature of germ cell tumors. This study offers valuable insights for clinical management and further regional research.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.

Primary intradural extraosseous Ewing's sarcoma of the L3 nerve root: illustrative case.

Ewing's sarcoma is an uncommon, aggressive malignancy that typically presents as an osseous lesion, most commonly in children and adolescents. Very rarely Ewing's sarcoma can present as an intradural extramedullary mass mimicking more common tumors. A 32-year-old female had a left L3 nerve root-associated lesion identified in the setting of recent-onset radiculopathy. Contrast-enhanced magnetic resonance imaging of the lumbar spine was favored to demonstrate a schwannoma or neurofibroma. Hemilaminectomy, facetectomy, and resection of the mass led to improved radiculopathy and a tissue diagnosis of Ewing's sarcoma. Immediate referral to medical oncology facilitated expeditious initiation of adjuvant chemotherapy and radiation. The differential diagnosis for newly identified nerve root-associated tumors should remain broad, including common benign pathologies and rare malignant entities. Tissue remains the gold standard for diagnosis, as preoperative imaging suggested a nerve sheath tumor. Malignant pathologies such as Ewing's sarcoma must be considered, especially in the setting of rapidly progressive symptoms or interval growth on serial imaging. Early diagnosis allows for the timely initiation of comprehensive oncological care. Long-term multidisciplinary follow-up is necessary for the surveillance of disease progression.

A potential new biomarker in HNSCC: metastasis suppressor protein 1 (MTSS1)

ObjectiveMetastasis suppressor protein 1 (MTSS1) is a prognostic tumour marker in different malignant epithelial tumour entities and previously mainly the MTSS1 expression was analyzed. This study evaluated the best analysis method as a prognosis and aggressiveness tumour marker in head and neck squamous cell carcinoma (HNSCC). Study DesignMTSS1 expression, MTSS1 intensity, interpretation MTSS1 score and MTSS1 edging score were analysed in formalin-fixed paraffin-embedded tissue slices of 60 patients with proven HNSCC and correlated with clinical and pathological outcome parameters. ResultsA lack of MTSS1 expression showed tumour aggressiveness, but surprisingly, mainly MTSS1 intensity was correlated with a worse patient outcome. There was a significant correlation between higher MTSS1 intensity and an increased risk for lymph node metastasis (p = 0.027) and a significant increased risk for extracapsular growth (p = 0.016). Furthermore, disease-specific survival was worse in cases with higher MTSS1 intensity (p = 0.001). ConclusionMTSS1 intensity has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision making.

Insights into the Distribution Patterns of Foot and Ankle Tumours: Update on the Perspective of a University Tumour Institute.

The rarity of foot and ankle tumours, together with the numerous histological entities, presents a challenge in accumulating sufficient patients to draw reliable conclusions. Therefore, we decided to present an update of a retrospective analysis of their distribution patterns, comprising 536 cases of foot and ankle tumours presented to our tumour board between June 1997 and June 2023. Our aim was to provide a comprehensive overview of the prevalence and distribution patterns of benign and malignant bone and soft tissue tumours of the foot and ankle. A total of 277 tumours involved bone (51.7%). Of these, 242 (87.4%) were benign and 35 (12.6%) were malignant. In addition, 259 soft tissue tumours (48.3%) were found, of which 191 (73.7%) were benign and 68 (26.3%) were malignant. The most common benign bone tumours were simple bone cysts, enchondromas, osteochondromas, aneurysmal bone cysts, and lipomas of bone. Common benign soft tissue tumours included a tenosynovial giant cell tumour, haemangioma, plantar fibromatosis, schwannoma, and lipoma. The most common malignant soft tissue tumours were synovial sarcoma, malignant melanoma, and myxofibrosarcoma. In terms of anatomical location, the hindfoot was the most common site (28.7%), followed by the midfoot (25.9%), ankle (25.4%), and forefoot (20.0%). The distribution of benign entities often follows typical patterns, which may facilitate an early diagnosis even without biopsy (e.g., simple bone cyst, plantar fibromatosis). On the other hand, the distribution patterns of many rare or malignant entities are inconsistent. Individual soft tissue malignancies occur very sporadically, even over long periods of time and in specialized tumour centres. It is therefore important to recognise that any suspicious mass in the foot and ankle must be considered a possible malignancy until proven otherwise.

Distribution Patterns of Benign and Malignant Bone and Soft Tissue Tumors and Tumor-like lesions in the Hindfoot and Ankle: A 12.5-year Analysis.

Benign and tumor-like lesions of the hindfoot and ankle are common, whereas malignant entities are rare. Accurate evaluation and timely management of these lesions can be challenging, making it crucial to understand their incidence and anatomic localization. This study retrospectively analyzed the distribution of benign and malignant bone and soft tissue tumors in the hindfoot and ankle. This study included patient data from a single center, such as age, sex, histologic diagnosis, and anatomic location over a 12.5 year period. Of the 105 cases reviewed, 19 cases (18.1%) were osseous lesions and 86 cases (81.9%) were soft tissue lesions. The latter were divided into 77 benign and 9 malignant cases, resulting in an overall malignancy rate of 8.6%. The most common osseous lesion was the intraosseous ganglion (n=12). The majority of benign soft tissue lesions (75.3%) were located in the hindfoot, with TGCT, schwannoma, and ganglion cysts being the most common types. The nine malignant cases were distributed among seven entities and were evenly distributed among both regions and sexes. Malignant cases had a higher mean age (59.2 years) compared to benign cases (40.8 years; p=0.001). Tumors, tumor-like lesions, and pseudotumors represent an important aspect of ankle pathology. The majority of focal masses and swellings are benign soft tissue or osseous lesions, but malignant entities can occur and may be mistaken for benign conditions. Preoperative imaging and histopathologic examination are essential, and preoperative presentation to a multidisciplinary tumor board is recommended in unclear cases.

Genomic Landscape Comparison of Cardiac versus Extra-Cardiac Angiosarcomas.

Angiosarcomas (ASs) are rare malignant vascular entities that can affect several regions in our body, including the heart. Cardiac ASs comprise 25-40% of cardiac sarcomas and can cause death within months of diagnosis. Thus, our aim was to identify potential differences and/or similarities between cardiac and extra-cardiac ASs to enhance targeted therapies and, consequently, patients' prognosis. Whole-transcriptome analysis of three cardiac and eleven extra-cardiac non-cutaneous samples was performed to investigate differential gene expression and mutational events between the two groups. The gene signature of cardiac and extra-cardiac non-cutaneous ASs was also compared to that of cutaneous angiosarcomas (n = 9). H/N/K-RAS and TP53 alterations were more recurrent in extra-cardiac ASs, while POTE-gene family overexpression was peculiar to cardiac ASs. Additionally, in vitro functional analyses showed that POTEH upregulation conferred a growth advantage to recipient cells, partly supporting the cardiac AS aggressive phenotype and patients' scarce survival rate. These features should be considered when investigating alternative treatments.

Deep learning based histological classification of adnex tumors

BackgroundCutaneous adnexal tumors are a diverse group of tumors arising from structures of the hair appendages. Although often benign, malignant entities occur which can metastasize and lead to patients´ death. Correct diagnosis is critical to ensure optimal treatment and best possible patient outcome. Artificial intelligence (AI) in the form of deep neural networks has recently shown enormous potential in the field of medicine including pathology, where we and others have found common cutaneous tumors can be detected with high sensitivity and specificity. To become a widely applied tool, AI approaches will also need to reliably detect and distinguish less common tumor entities including the diverse group of cutaneous adnexal tumors. MethodsTo assess the potential of AI to recognize cutaneous adnexal tumors, we selected a diverse set of these entities from five German centers. The algorithm was trained with samples from four centers and then tested on slides from the fifth center. ResultsThe neural network was able to differentiate 14 different cutaneous adnexal tumors and distinguish them from more common cutaneous tumors (i.e. basal cell carcinoma and seborrheic keratosis). The total accuracy on the test set for classifying 248 samples into these 16 diagnoses was 89.92 %. Our findings support AI can distinguish rare tumors, for morphologically distinct entities even with very limited case numbers (< 50) for training. ConclusionThis study further underlines the enormous potential of AI in pathology which could become a standard tool to aid pathologists in routine diagnostics in the foreseeable future. The final diagnostic responsibility will remain with the pathologist.

PATH-26. A RARE CASE OF EXOPHYTIC PILOCYTIC ASTROCYTOMA DIAGNOSED VIA MOLECULAR TESTING

Abstract INTRODUCTION Pilocytic astrocytoma (PA) is a WHO grade 1 neoplasm that can share histological and radiological features with more malignant entities, including high grade astrocytoma with piloid features. In cases where the differential remains broad after histopathological examination, DNA methylation analysis and next generation sequencing can contribute significantly to making an accurate diagnosis. Machine learning has also played a role in developing multiple classifying algorithms which group tumors by their methylation status. CASE We report a case of an exophytic left frontal mass with adjacent bone erosion that preoperatively was favored to be a meningioma. Intraoperatively, the mass was found to be cortically based. With histopathologic review at two centers, the diagnosis remained IDH wildtype low-grade glioma not otherwise specified. The clinical treatment team interpreted the post-operative increase in T2 signal as radiographic progression consistent with high grade glioma and planned to proceed with chemoradiation. Patient elected for further evaluation; methylation array profiling and next generation sequencing identified a KIAA1549::BRAF fusion, consistent with a final diagnosis of pilocytic astrocytoma, a WHO Grade 1 Glioma. Given the favorable prognosis following gross total resection, the patient was recommended active surveillance and radiation and chemotherapy treatment planning was stopped. DISCUSSION This is a rare case of an exophytic pilocytic astrocytoma in which the tumor’s atypical histologic and radiographic appearance increased the likelihood of diagnostic errors. This case illustrates the clinical importance of utilizing methylation array profiling and next-generation sequencing to confirm a diagnosis.

Combined Photon and Carbon Ion Radiation Therapy for Sinonasal Malignancies: Results of the HIT–SNT Prospective Phase 2 Trial

Radiation treatment of sinonasal malignancies is a challenging task due to proximity to critical structures of the head and neck and skull base. Local tumor control is highly dose-dependent, but dose application is limited due to accompanying toxicity and dose constraints. To evaluate the toxicity and efficacy of combined radiation treatment with intensity-modulated radiation therapy (IMRT) and carbon ion boost, we conducted a prospective phase 2 IMRT-Heidelberg Ion-Beam Therapy Sinonasal Tumors (HIT-SNT) trial. Between 2011 and 2019, we treated 35 patients with histologically proven, incompletely resected or inoperable adeno- (51%) or squamous cell carcinoma (49%) of the paranasal sinuses with combined IMRT (50 Gy) and carbon ion boost (24 Gy relative biologic effectiveness) to a total dose of 74 Gy. Acute mucositis Common Terminology Criteria for Adverse Events (CTCAE) grade 3 occurred in 12% of patients (n = 4) and was accompanied by odynophagia CTCAE grade 3. Except for 1 case of grade 3 weight loss, no other acute high-grade toxicity (grade 3-4) was observed. In a small patient cohort of 15 patients eligible for long-term follow-up we have seen no high-grade (grade ≥3) long-term side effects 2 years after radiation therapy. None of these patients suffered from therapy-associated vision or hearing loss. Secondary endpoints were 2-year overall survival, 2-year local progression-free survival, 2-year progression-free survival, and 2-year metastases-free survival with 79.4%, 61.8%, 61.8%, and 64.8%, respectively. To our knowledge, this is the first prospective data on toxicity and outcome of bimodal radiation therapy for the rare entity of sinonasal malignancies. Our study shows a low rate of CTCAE-reported acute toxicity with reasonable tumor control and survival rates after bimodal radiation therapy, which therefore remains a therapy approach to be further evaluated.

Clinical and cytohistomorphological evaluation of peripheral nerve sheath tumours with special reference to immunohistochemical diversity in a tertiary care hospital

Peripheral Nerve Sheath Tumours (PNST), though have a frequent prevalence, are diagnostically challenging. There is a wide spectrum of lesions ranging from benign entities like neurofibroma, Schwannoma, perineurioma to malignant entities like malignant peripheral nerve sheath tumours (MPNST), malignant granular cell tumour and malignant perineurioma. Since there is an overlap with other spindle and round cell tumours, IHC and molecular studies are needed to provide a clear distinction between different tumour types. It was a 5 years observational study (3 years retrospective and 2 years prospective) conducted in the Department of Pathology, JNMCH, AMU from 2015-2020. . History and relevant clinical findings were retrieved from the archives of both the Histopathology and Cytopathology Lab. Imprints as well as FNA smears were included from Cytopathology Lab and biopsies and resection specimen from Histopathology Lab. Immunohistochemistry was applied wherever necessary. A total of 82 cases were diagnosed over a 5 year period out of which 70 were benign and 12 malignant. Male preponderance was seen. Benign tumours comprised mostly of Neurofibroma and Schwannoma and there were 12 cases of MPNST. Correlation was established between Cytopathological and Histopathological findings and IHC, mostly S100 proved useful in differentiating it from other malignant spindle cell tumours. The differential diagnoses of these tumours has always posed a problem given their monotonous appearance and clinical overlap. This study, therefore, aims to analyse the diverse morphological features of Peripheral Nerve Sheath Tumours in the light of cytopathological and histopathological findings and immunohistochemistry.

Laryngeal coccidioidomycosis in adults: systematic review of the literature and a case report

Abstract BACKGROUND. Coccidioidomycosis spp. is a dimorphic fungus endemic to the southwestern United States and northern Mexico. Incidences in high-risk locations have increased over the last years. MATERIAL AND METHODS. A systematic review has been carried out following the PRISMA guidelines of the reports found in PubMed, Scopus, Google Scholar databases from 1953 to 2023. We included articles written in the English language, with the following keywords “laryngeal” and “coccidioidomycosis” and “adults”, "upper respiratory tract" and "coccidioidomycosis" and "adults". RESULTS. In the review, we could access 8 publications with a total of 10 cases in which 7 men and 3 women were reported, with a mean age of 49.3 years. The ten reported cases were from the southern region of the United States, which borders our state of Sonora in the north. Also, we report the case of a 24-year-old male patient, who presented a chronic picture of more than 1 year with dysphonia, worsening in the last month. He underwent direct laryngoscopy with biopsy, resulting in the diagnosis of laryngeal coccidioidomycosis. Our patient had multiple comorbidities, among which chronic kidney disease in treatment with peritoneal dialysis, erythropoietin and prednisone, with a history of renal transplant in 2017, rejected in 2019. CONCLUSION. Laryngeal coccidioidomycosis is a diagnostic challenge for the clinician, its characteristics may appear to be a malignant entity, up to the formation of abscesses and even present bone destruction. The geographical area in which we are located makes it necessary to always include coccidioidomycosis as a pathology to rule out in our patients.

Decision-Making in Clival Mass Lesions: Risk Factors for Malignant Disease and an Illustrative Case Example.

Introduction Clival tumors are rare and heterogeneous. Although some benign prototypical sellar lesions may present as clival tumors, the likelihood of malignant disease is higher. Here we define a novel algorithm for the workup and management of clival masses through an illustrative case of colorectal adenocarcinoma metastasis to the clivus. Methods In this case report, the best practice guidelines for managing clival masses are described through a literature review and refined by senior author consensus. We conducted a focused systematic review to characterize the present case in the context of clival metastasis from gastrointestinal malignancy. Results An 83-year-old woman presented with 4 weeks of headaches and blurry vision. Examination revealed partial right abducens and left oculomotor palsies. Magnetic resonance imaging (MRI) identified a large, weakly enhancing sellar and clival mass with sphenoid sinus extension. An aggressive subtotal endoscopic endonasal resection was performed with removal of all sphenoid, clival, and sellar disease without cavernous sinus wall resection. Pathology confirmed colorectal adenocarcinoma; computed tomography (CT) imaging identified an ascending colon mass with metastases to the liver and mesenteric nodes. Palliative oncologic therapies were recommended, but she elected hospice, and died 3 months after initial presentation. Gastrointestinal clival metastases are exceedingly rare among sellar and clival pathologies, with eight prior cases reported, most of which presented with diplopia from abducens nerve involvement. Conclusion Clival masses are uncommon skull base lesions that are associated with more aggressive diseases. We present a consolidated framework for decision-making in these challenging patients, alongside an unusual case example that illustrates the importance of increased suspicion for malignant clinical entities in this setting.

Pancreatic cystic neoplasms: Still high rates of preoperative misdiagnosis in the guidelines and endoscopic ultrasound era

BackgroundA wrong diagnosis of nature is common in pancreatic cystic neoplasms. The aim of the current study is to reappraise the diagnostic errors for presumed pancreatic cystic neoplasms in patients undergoing surgery. MethodsAll pancreatic resections for presumed pancreatic cystic neoplasms following international guidelines between 2011 and 2020 were analyzed. Misdiagnosis was defined as the discrepancy between preoperative diagnosis of nature and final pathology. Mismatch was defined as the discrepancy between the preoperative suspect of malignancy (or its absence) and final pathology. ResultsA total of 601 patients were included. Endoscopic ultrasound was performed in 301 (50%) patients. Overall misdiagnosis and mismatch were 19% and 34%, respectively, with no significant benefit for those patients who underwent endoscopic ultrasound. The highest rate of misdiagnosis was reached for cystic neuroendocrine tumors (61%) and the lowest for solid pseudopapillary tumors (6%). Several diagnostic errors had clinical relevance, including 7 (13%) presumed serous cystic neoplasms eventually found to be other malignant entities, 50 (24%) intraductal papillary mucinous neoplasms with high-risk stigmata revealed to be non-malignant, and 38 (33%) intraductal papillary mucinous neoplasms without high-risk stigmata revealed to be malignant at final pathology. A preoperative presumption of malignant mucinous cystic neoplasm was correct in only 20 (16%) patients. ConclusionsDespite not always being clinically relevant, diagnostic errors are still common among resected pancreatic cystic neoplasms when applying international guidelines. New diagnostic tools beyond endoscopic ultrasound are needed to refine the diagnosis of those lesions at higher risk for unnecessary surgery or accidentally observed, nevertheless being malignant.

An exploratory study of cell stiffness as a mechanical label-free biomarker across multiple musculoskeletal sarcoma cells

BackgroundCancer cells are characterized by changes in cell cytoskeletal architecture and stiffness. Despite advances in understanding the molecular mechanisms of musculoskeletal cancers, the corresponding cellular mechanical properties remain largely unexplored. The aim of this study was to investigate the changes in cellular stiffness and the associated cytoskeleton configuration alterations in various musculoskeletal cancer cells.MethodsCell lines from five main sarcoma types of the musculoskeletal system (chondrosarcoma, osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) as well as their healthy cell counterparts (chondrocytes, osteoblasts, mesenchymal stem cells, fibroblasts, skeletal muscle cells) were subjected to cell stiffness measurements via atomic force microscopy (AFM). Biochemical and structural changes of the cytoskeleton (F-actin, β-tubulin and actin-related protein 2/3) were assessed by means of fluorescence labelling, ELISA and qPCR.ResultsWhile AFM stiffness measurements showed that the majority of cancer cells (osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) were significantly less stiff than their corresponding non-malignant counterparts (p < 0.001), the chondrosarcoma cells were significant stiffer than the chondrocytes (p < 0.001). Microscopically, the distribution of F-actin differed between malignant entities and healthy counterparts: the organisation in well aligned stress fibers was disrupted in cancer cell lines and the proteins was mainly concentrated at the periphery of the cell, whereas β-tubulin had a predominantly perinuclear localization. While the F-actin content was lower in cancer cells, particularly Ewing sarcoma (p = 0.018) and Fibrosarcoma (p = 0.023), this effect was even more pronounced in the case of β-tubulin for all cancer-healthy cell duos. Interestingly, chondrosarcoma cells were characterized by a significant upregulation of β-tubulin gene expression (p = 0.005) and protein amount (p = 0.032).ConclusionModifications in cellular stiffness, along with structural and compositional cytoskeleton rearrangement, constitute typical features of sarcomas cells, when compared to their healthy counterpart. Notably, whereas a decrease in stiffness is typically a feature of malignant entities, chondrosarcoma cells were stiffer than chondrocytes, with chondrosarcoma cells exhibiting a significantly upregulated β-tubulin expression. Each Sarcoma entity may have his own cellular-stiffness and cytoskeleton organisation/composition fingerprint, which in turn may be exploited for diagnostic or therapeutic purposes.