ABSTRACT
We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.
Subject(s)
Mycobacterium avium-intracellulare Infection , Humans , Male , Mycobacterium avium-intracellulare Infection/diagnosis , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/diagnostic imaging , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/drug therapy , Spinal Cord Diseases/microbiology , Adult , HIV Infections/complicationsABSTRACT
Intratumoral hypoxia correlates with metastasis and poor survival in patients with sarcoma. Using an impedance sensing assay and a zebrafish intravital microinjection model, we demonstrated here that the hypoxia-inducible collagen-modifying enzyme lysyl hydroxylase PLOD2 and its substrate collagen type VI (COLVI) weaken the lung endothelial barrier and promote transendothelial migration. Mechanistically, hypoxia-induced PLOD2 in sarcoma cells modified COLVI, which was then secreted into the vasculature. Upon reaching the apical surface of lung endothelial cells, modified COLVI from tumor cells activated integrin ß1 (ITGß1). Furthermore, activated ITGß1 colocalized with Kindlin2, initiating their interaction with F-actin and prompting its polymerization. Polymerized F-actin disrupted endothelial adherens junctions and induced barrier dysfunction. Consistently, modified and secreted COLVI was required for the late stages of lung metastasis in vivo. Analysis of patient gene expression and survival data from The Cancer Genome Atlas (TCGA) revealed an association between the expression of both PLOD2 and COLVI and patient survival. Furthermore, high levels of COLVI were detected in surgically resected sarcoma metastases from patient lungs and in the blood of tumor-bearing mice. Together, these data identify a mechanism of sarcoma lung metastasis, revealing opportunities for therapeutic intervention. SIGNIFICANCE: Collagen type VI modified by hypoxia-induced PLOD2 is secreted by sarcoma cells and binds to integrin ß1 on endothelial cells to induce barrier dysfunction, which promotes sarcoma vascular dissemination and metastasis.
Subject(s)
Lung Neoplasms , Sarcoma , Humans , Animals , Mice , Collagen Type VI/genetics , Collagen Type VI/metabolism , Endothelial Cells/metabolism , Zebrafish/metabolism , Actins , Integrin beta1 , Hypoxia , Sarcoma/metabolism , Lung/pathologyABSTRACT
Different authors have recently described a subtype of lipoma characterized by variation of adipocyte size, single cell fat necrosis, and a subset with minimal to mild nuclear atypia, and termed these as anisometric cell/dysplastic lipoma (AC/DL). These lipomas follow a benign course and rarely recur. In 3 examples, AC/DL has occurred in patients with childhood retinoblastoma (RB). We report another such example where multiple AC/DL occurred in the neck and back of a 30-year-old male who had germline RB1 gene deletion and bilateral RB in infancy. On excision, all tumors histologically showed similar morphology of adipocyte anisometry, focal single cell necrosis with surrounding binucleated or multinucleated histiocytes, hyperchromatic and minimally atypical lipocyte nuclei, vacuolated Lockhern change, rare foci of fibromyxoid change, occasional mononuclear cell clusters around capillaries, and loss of RB1 immunostaining. Unequivocal atypical cells, lipoblasts, floret-nucleated or multinucleated giant cells were absent. Molecular analysis of tumor cells showed monoallelic RB1 gene loss without amplification of MDM2 and CDK4 genes. Short-term follow up did not show tumor recurrence. AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.
Subject(s)
Lipoma , Liposarcoma , Retinal Neoplasms , Retinoblastoma , Soft Tissue Neoplasms , Male , Humans , Child , Adult , Retinoblastoma/genetics , Soft Tissue Neoplasms/pathology , Biomarkers, Tumor/analysis , Lipoma/genetics , Lipoma/pathology , Liposarcoma/pathology , HyperplasiaABSTRACT
Myofibroblastoma is a rare benign mesenchymal tumor first described in the breast. It is also known as mammary-type myofibroblastoma outside of the breast, more frequently located along the embryonic milk line. Exceptionally, myofibroblastoma can occur at visceral locations. We present a case of myofibroblastoma detected incidentally in the liver. A well-circumscribed mass, grossly measuring 6.2â cm in the liver parenchyma, was found on imaging studies. Histologically, the lesion is characterized by benign spindle cells in a hyalinized collagenous stroma, with positive staining for SMA and ER, focal positivity for CD34, negative for desmin, and loss of RB1. This rare tumor at such an unusual location makes it diagnostically challenging, especially on core biopsy of the lesion. To our knowledge, this is the second case of myofibroblastoma in the liver reported in the English literature and the first such case with a detailed pathology description.
Subject(s)
Biomarkers, Tumor , Neoplasms, Muscle Tissue , Humans , Immunohistochemistry , Neoplasms, Muscle Tissue/diagnosis , Neoplasms, Muscle Tissue/surgery , Neoplasms, Muscle Tissue/pathology , Breast/pathology , Liver/pathologyABSTRACT
Atypical spindle cell and pleomorphic lipomatous tumor (ASCPLT) is a rare lipomatous neoplasm that was recently introduced into the World Health Organization Classification of Soft Tissue and Bone tumors as a distinct entity. ASCPLT has potential for local recurrence but does not metastasize. This biologic behavior separates ASCPLT from its morphologic mimics. Ocular adnexal ASCPLT has not been previously reported. Described herein are two patients with ASCPLT. The subcutaneous orbital rim lesion featured markedly pleomorphic spindle and multinucleated cells. The eyelid lesion was dominated by atypical spindle cells in a background of mature adipocytes. Both neoplasms demonstrated infiltrative margins, rare mitotic figures, immunoreactivity for CD34 and loss of Rb1, and the absence of MDM2 amplification by fluorescence in situ hybridization. Recognition of ASCPLT in the differential of ocular adnexal neoplasms may lead to a re-evaluation of morphologically similar tumors, which may have varied biologic behavior and warrant a different management approach.
Subject(s)
Biological Products , Lipoma , Liposarcoma , Humans , Lipoma/diagnosis , In Situ Hybridization, Fluorescence , Biomarkers, Tumor , Liposarcoma/diagnosis , Diagnosis, DifferentialABSTRACT
Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumor that primarily involves the extremities. We report a case of a 30-year-old never-smoker man who presented with hematuria, dysuria, and constipation at an outside hospital. He was diagnosed with and treated for multiple episodes of urinary tract infection. However, he continued to have voiding symptoms for which a cystoscopy was performed and revealed a bladder neck mass. He underwent transurethral resection of a bladder tumor and was diagnosed with muscle-invasive urothelial carcinoma, nested variant, at an outside hospital. Subsequent to this diagnosis he transferred his care to our center. In-house imaging revealed a large vascular mass involving the prostate and pushing against the bladder base. Prostate needle biopsies were performed and revealed an epithelioid neoplasm with a nested growth pattern composed of cells with a moderate amount of eosinophilic cytoplasm, mildly pleomorphic nuclei, and occasional prominent nucleoli. Since the findings were not classic for urothelial carcinoma or for prostate cancer, we included a wider differential of poorly differentiated carcinoma, sarcoma, and paraganglioma. A wide panel of keratin stains was negative, ETS (erythroblast transformation-specific)-related gene highlighted an extensive vascular network and neuroendocrine stains were all negative. A transcription factor E3 fluorescent in-situ hybridization was positive and subsequently, an ASPSCR1 gene rearrangement was demonstrated. The outside hospital transurethral resection of bladder tumor was obtained for review and the tumor was morphologically similar to that seen on the in-house prostate needle biopsies. Based on the above findings a final diagnosis of primary ASPS of the prostate with involvement of the bladder was made. The patient was later diagnosed with bilateral lung metastases. He was treated with pazopanib, radiation therapy, and cystoprostatectomy and is symptom-free on a 15-month follow-up.
Subject(s)
Carcinoma, Transitional Cell , Sarcoma, Alveolar Soft Part , Soft Tissue Neoplasms , Urinary Bladder Neoplasms , Male , Humans , Adult , Sarcoma, Alveolar Soft Part/diagnosis , Sarcoma, Alveolar Soft Part/genetics , Sarcoma, Alveolar Soft Part/surgery , Prostate/pathology , Urinary Bladder Neoplasms/diagnosis , Soft Tissue Neoplasms/pathologyABSTRACT
The PLEKHH2::ALK fusion is a rarely reported gene fusion identified predominantly in lung adenocarcinomas. Tumors with this fusion have been reported to be of durable response to ALK inhibitors. We herein present the case of a 21-year-old woman with a histomorphologically heterogenous mesenchymal neoplasm of the pelvis, expressing both s100 and CD34, with subsequently identified PLEKHH2::ALK fusion. To our knowledge, only a single mesenchymal neoplasm with this gene fusion has been previously reported. We propose that this tumor represents one with a novel ALK fusion in the emerging family of s100 and CD34 expressing mesenchymal neoplasms with oncogenic kinase alterations akin to NTRK -rearranged mesenchymal neoplasms, rather than inflammatory myofibroblastic tumor. Importantly, this tumor demonstrated a significant response to the ALK inhibitor brigatinib.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasms, Connective and Soft Tissue , Adult , Cytoskeletal Proteins/genetics , Female , Gene Fusion , Humans , Lung Neoplasms/pathology , Oncogene Proteins, Fusion/genetics , Protein Kinase Inhibitors/therapeutic use , Receptor Protein-Tyrosine Kinases/genetics , S100 Proteins , Young AdultABSTRACT
Low-grade fibromyxoid sarcoma (LGFMS) is a histopathologically deceptive soft tissue neoplasm with bland cytology, which is typically encountered in deep soft tissue of adults. We report two cases of superficial LGFMS in young patients (16 and 21 years old, respectively), which were difficult to diagnose on histopathologic and clinical findings alone. LGFMS commonly mimics benign neoplasms such as cellular neurothekeoma, fibromatosis, neurofibroma, and perineurioma. Malignancies included in the differential diagnosis are soft tissue neoplasms such as dermatofibrosarcoma protuberans and myxofibrosarcoma. A high degree of reported variation in pattern and cellularity among LGFMS further complicates the diagnosis. Careful examination and appropriate immunohistochemistry panels including MUC4 are essential for narrowing the differential diagnosis. Molecular studies for possible FUS translocation can confirm the diagnosis of LGFMS. Sufficient sampling and workup of these lesions are critical, especially in younger patients. Young age and superficial presentation can easily sway dermatopathologists/dermatologists toward an incorrect diagnosis of benignancy.
Subject(s)
Fibroma , Fibrosarcoma , Nerve Sheath Neoplasms , Soft Tissue Neoplasms , Adolescent , Adult , Fibroma/diagnosis , Fibroma/pathology , Fibrosarcoma/diagnosis , Fibrosarcoma/pathology , Humans , Immunohistochemistry , Soft Tissue Neoplasms/pathology , Young AdultABSTRACT
BACKGROUND: Although meningiomas are the most common central nervous system neoplasms, extracranial metastases are exceedingly rare. There are even fewer reports of metastatic meningiomas to the neck. METHODS: We described a patient with multiply recurrent orbital meningioma with metastasis to the neck found incidentally during neck exploration for composite resection and free tissue reconstruction. We performed a systematic review for all records pertaining to metastatic meningiomas to the cervical regions. RESULTS: We found 9 previous reports of cervical metastatic meningiomas. Almost all cases underwent extensive local resection. There was no evidence of an association between the histological grade of the tumor and risk of metastasis to the neck. Cervical lymph node dissemination is more common in patients presenting after previous primary tumor resection. CONCLUSIONS: In the context of a neck mass, our findings suggest that metastatic meningioma should be included in the differential diagnosis, especially in patients with previous resections.
Subject(s)
Meningeal Neoplasms , Meningioma , Neoplasms, Second Primary , Humans , Lymph Nodes/pathology , Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Meningioma/diagnosis , Meningioma/pathology , Meningioma/surgery , Neck/pathology , Neoplasm Recurrence, Local/pathologyABSTRACT
Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.
Subject(s)
Carcinoma, Endometrioid/pathology , Dermoid Cyst/pathology , Endometrial Neoplasms/pathology , Granuloma/pathology , Keratins/metabolism , Ovarian Neoplasms/pathology , Peritoneal Diseases/pathology , Biomarkers/metabolism , Carcinoma, Endometrioid/complications , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/metabolism , Dermoid Cyst/complications , Dermoid Cyst/diagnosis , Dermoid Cyst/metabolism , Diagnosis, Differential , Endometrial Neoplasms/complications , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/metabolism , Female , Frozen Sections , Granuloma/diagnosis , Granuloma/etiology , Granuloma/metabolism , Humans , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/metabolism , Peritoneal Diseases/diagnosis , Peritoneal Diseases/etiology , Peritoneal Diseases/metabolismABSTRACT
Florid reactive periostitis ossificans (FRPO) is a benign juxta-cortical lesion of unknown etiology which most commonly occurs in the hands and feet. We report the radiographic, CT, and MR features of a pathologically confirmed FRPO in the distal femur, a location in which only a handful of cases has been reported. A 26-year-old male who presented with distal thigh pain initially underwent radiograph and CT, which illustrated a well-circumscribed, ossified lesion associated with the cortex of the femur without contiguity with the medullary canal. A subsequent MRI demonstrated heterogeneous signal intensity corresponding to the ossified portion of the lesion with a T2 hyperintense cartilaginous cap and surrounding edema. The lesion was surgically excised and pathologic diagnosis of FRPO, a mixture of osteoid, mature bone, cartilage and fibrous tissue, with associated inflammatory cells, was confirmed. Follow up four months after surgery revealed significant improvement in the patient's pain.
ABSTRACT
DNA detection plays an important role in the rapid screening of cancers and early diagnosis of infectious diseases. Here, we developed a simple, versatile, electric field-enhanced (EFE), electrochemical CRISPR biosensor to detect DNA targets in a homogeneous solution phase. To improve the detection sensitivity, we applied a pulsed electric field to enrich nucleic acids on the electrode surface. The EFE electrochemical CRISPR biosensor takes advantage of the diffusivity difference between electrochemical oligonucleotide probes and CRISPR-cleaved probes toward a negatively charged working electrode, enabling simple and sensitive electrochemical detection of DNA without the need for complicated immobilization processing of electrochemical probes. Our developed CRISPR biosensor directly detects unamplified human papillomavirus-16 (HPV-16) DNA with a sensitivity of 1 pM. Further, the EFE electrochemical CRISPR biosensor coupled with recombinase polymerase amplification (RPA) successfully detects HPV-16 DNA in clinical samples. Thus, the EFE electrochemical CRISPR biosensor provides a simple, robust, and sensitive detection method for nucleic acid-based molecular diagnostics.
Subject(s)
Biosensing Techniques , Nucleic Acids , CRISPR-Cas Systems , Clustered Regularly Interspaced Short Palindromic Repeats , DNA/genetics , Electrochemical Techniques , HumansABSTRACT
This review provides a conceptual approach to dedifferentiation across a variety of tumor types, with particular attention to genetic events that tie together morphologically disparate areas of these neoplasms. First, working definitions of the terms differentiated, undifferentiated, and dedifferentiated are developed. Then, specific examples of tumors with a particular propensity for undergoing dedifferentiation are highlighted, with emphasis on both immunohistochemical studies and molecular lesions that enable surgical pathologists to establish diagnostic clarity in morphologically vexing situations. Throughout this review, the historical arc of the literature is followed, and therefore the discussion of specific tumor types begins with dedifferentiated chondrosarcoma, the neoplasm that inspired the terminology regarding dedifferentiation that remains in use today. Selected other sarcomas with well-established pathways of dedifferentiation are subsequently discussed, followed by descriptions of this process in subtypes of carcinoma and melanoma.
Subject(s)
Melanoma , Sarcoma , Soft Tissue Neoplasms , Cell Differentiation , HumansABSTRACT
High-grade serous carcinoma has a variety of different growth patterns, but is typically easily recognizable to pathologists and rarely confused with serous borderline tumors. We report a case of a 71-yr-old woman with a unilateral 5.1 cm ovarian cyst with small papillary projections on contrast-enhanced magnetic resonance imaging of the pelvis. Histologic examination showed a noninvasive papillary neoplasm with hierarchical branching and epithelial proliferation, and thus, at low magnification, bearing a striking resemblance to a serous borderline tumor. However, a more careful examination demonstrated high-grade cytologic features, nuclear pleomorphism, and abundant mitotic activity, suggestive of high-grade serous carcinoma. The morphology and immunohistochemical profile of this lesion is consistent with a rare, purely noninvasive growth pattern of high-grade serous carcinoma. This lesion represents the "far left" of the high-grade ovarian serous carcinoma morphologic spectrum and can mimic a serous borderline tumor.
Subject(s)
Cystadenocarcinoma, Serous/diagnostic imaging , Neoplasms, Glandular and Epithelial/diagnostic imaging , Ovarian Cysts/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Aged , Cystadenocarcinoma, Serous/pathology , Female , Humans , Hysterectomy , Immunohistochemistry , Magnetic Resonance Imaging , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Cysts/pathology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgeryABSTRACT
INTRODUCTION: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits. METHODS: Creation of consensus document. RESULTS: The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system. CONCLUSIONS: These guidelines support an ethical approach for the management of head and neck cancers during the COVID-19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.
Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Head and Neck Neoplasms/therapy , Infection Control/standards , Medical Oncology/standards , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Ambulatory Care/standards , COVID-19 , Combined Modality Therapy , Continuity of Patient Care/standards , Coronavirus Infections/diagnosis , Head and Neck Neoplasms/diagnosis , Humans , Multi-Institutional Systems , Otorhinolaryngologic Surgical Procedures/standards , Palliative Care/standards , Patient Safety , Pennsylvania , Personal Protective Equipment , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Terminal Care/standards , Tertiary Care CentersABSTRACT
Rapid diagnostics of infectious diseases and accurate identification of their causative pathogens play a crucial role in disease prevention, monitoring, and treatment. Conventional molecular detection of infectious pathogens requires expensive equipment and well-trained personnel, thus limiting its use in centralized clinical laboratories. To address this challenge, a portable smartphone-based quantitative molecular detection platform, termed "smart connected pathogen tracer" (SCPT), has been developed for pathogen monitoring and disease surveillance. The platform takes advantage of synergistically enhanced colorimetric loop-mediated isothermal amplification (LAMP) assay and smartphone-based color analysis, enabling simple, rapid and reliable nucleic acid quantification without need for expensive fluorescence detection equipment. The SCPT platform has been successfully applied to quantitatively detect: i) HPV DNA in saliva and clinical vaginal swab samples, and ii) HIV RNA in plasma samples with comparable sensitivity to state-of-art machine. It has also been demonstrated for disease spatiotemporal mapping and pathogen tracking by wireless connection and web-based surveillance. Such simple, cost-affordable, portable molecular detection platform has great potential for on-site early disease detection, remote healthcare monitoring, and epidemic surveillance.
Subject(s)
HIV Testing/methods , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Papillomavirus Infections/diagnosis , Smartphone , Colorimetry , DNA, Viral/analysis , Female , Geographic Information Systems , HIV Testing/instrumentation , Humans , Lab-On-A-Chip Devices , Molecular Diagnostic Techniques/instrumentation , Papillomavirus Infections/virology , RNA, Viral/blood , Saliva/virology , Vagina/virologyABSTRACT
After dedicated CT and MRI, Ga-DOTATATE PET/CT was performed in a patient with a temporal bone mass with primary diagnostic considerations of an endolymphatic sac tumor versus a glomus jugulotympanicum paraganglioma. The Ga-DOTATATE PET showed mild radiotracer uptake in the mass (SUVmax, 10.9). After surgical resection, pathology revealed an endolymphatic sac tumor. Immunohistochemical staining demonstrated somatostatin receptor type 2A expression in the vasculature of the mass, but not in the tumor cells.
Subject(s)
Ear Neoplasms/diagnostic imaging , Ear Neoplasms/pathology , Endolymphatic Sac/diagnostic imaging , Endolymphatic Sac/pathology , Organometallic Compounds/metabolism , Positron Emission Tomography Computed Tomography , Adult , Aged , Diagnosis, Differential , Ear Neoplasms/metabolism , Endolymphatic Sac/metabolism , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Paraganglioma/diagnosis , Receptors, Somatostatin/metabolismABSTRACT
Recently, CRISPR-Cas technology has opened a new era of nucleic acid-based molecular diagnostics. However, current CRISPR-Cas-based nucleic acid biosensing has a lack of the quantitative detection ability and typically requires separate manual operations. Herein, we reported a dynamic aqueous multiphase reaction (DAMR) system for simple, sensitive and quantitative one-pot CRISPR-Cas12a based molecular diagnosis by taking advantage of density difference of sucrose concentration. In the DAMR system, recombinase polymerase amplification (RPA) and CRISPR-Cas12a derived fluorescent detection occurred in spatially separated but connected aqueous phases. Our DAMR system was utilized to quantitatively detect human papillomavirus (HPV) 16 and 18 DNAs with sensitivities of 10 and 100 copies within less than 1 h. Multiplex detection of HPV16/18 in clinical human swab samples were successfully achieved in the DAMR system using 3D-printed microfluidic device. Furthermore, we demonstrated that target DNA in real human plasma samples can be directly amplified and detected in the DAMR system without complicated sample pretreatment. As demonstrated, the DAMR system has shown great potential for development of next-generation point-of-care molecular diagnostics.
Subject(s)
Bacterial Proteins/genetics , CRISPR-Associated Proteins/genetics , CRISPR-Cas Systems/genetics , DNA, Viral/genetics , Endodeoxyribonucleases/genetics , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Real-Time Polymerase Chain Reaction , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Water/chemistryABSTRACT
Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy with a poor prognosis, and pathologically, it is a diagnosis of exclusion. Rendering this diagnosis can be challenging in practice because of the large number of diverse entities in the differential diagnosis. We encountered an index case of a sinonasal carcinoma otherwise diagnosable as SNUC which, on further investigation, demonstrated strong and diffuse P16 expression, as well as diffuse expression of high-risk human papillomavirus (hrHPV) RNA by in situ hybridization (ISH). We therefore hypothesized that a subset of cases previously diagnosed as SNUC may in fact harbor transcriptionally active hrHPV. We further investigated a cohort of 25 SNUC cases in our pathology archives and performed ISH for hrHPV RNA on cases that demonstrated >70% nuclear and cytoplasmic P16 expression, criteria which, in other anatomic sites, correlates strongly with the presence of hrHPV. Twelve of 25 SNUC cases were P16 positive, and of these, 5 were positive for hrHPV by ISH. Thus, 20% of all SNUC cases in this cohort harbored transcriptionally active hrHPV. Herein, we report a clinical and pathologic analysis of these cases, including differential diagnostic considerations and comparison of their clinical behavior with SNUC cases that are negative for hrHPV by ISH.
Subject(s)
Carcinoma/virology , Maxillary Sinus Neoplasms/virology , Papillomavirus Infections/complications , Adult , Aged , Cyclin-Dependent Kinase Inhibitor p16/analysis , Female , Humans , In Situ Hybridization , Male , Middle Aged , Papillomaviridae , Retrospective StudiesABSTRACT
Mucinous metaplasia in Warthin tumor (WT) is a recognized phenomenon. Nevertheless, its presence can create a diagnostic challenge in the distinction from the newly proposed variant of mucoepidermoid carcinoma (MEC), Warthin-like MEC. In this study, we evaluated the significance and diagnostic relevance of mucinous metaplasia in WTs. A total of 30 WTs diagnosed based on resection specimens formed the basis of this retrospective study. Mucicarmine staining was performed to identify mucinous metaplasia, and fluorescence in situ hybridization (FISH) analysis was used to detect MAML2 gene rearrangement. After review, one MAML2 rearranged case was reclassified as Warthin-like MEC as the classic bilayered epithelium in WT was not identified. The diagnosis of WT was confirmed in the remaining 29 cases. Mucinous metaplasia was encountered in 24 WTs (83%), with 14% (4/29) having an abundant amount. We found that mucinous metaplasia correlated with tumor size (p < 0.05). Age and sex distribution were similar in WT cases with or without mucinous metaplasia. In addition, neither the presence of squamous metaplasia nor the time interval between fine-needle aspiration and surgery was related to mucinous metaplasia (p > 0.05). The MAML2 FISH analyses performed in 18 WTs with variable amounts of mucinous metaplasia were negative for rearrangement. In conclusion, mucinous metaplasia is fairly common in WTs and shows a significant correlation with tumor size. Therefore, caution should be taken to avoid overinterpretation of WT with mucinous metaplasia as MEC in cases showing the classic bilayered oncocytic lining epithelium.