The role of human papillomavirus (HPV) as an etiologic and transformational agent in inverted Schneiderian papilloma (ISP) is unclear. Indeed, reported detection rates of HPV in ISPs range from 0 to ...100%. The true incidence has been confounded by a tendency to conflate high- and low-risk HPV types and by the inability to discern biologically relevant from irrelevant HPV infections. The recent development of RNA in situ hybridization for high-risk HPV E6/E7 mRNA now allows the direct visualization of transcriptionally active high-risk HPV in ISP, providing an opportunity to more definitively assess its role in the development and progression of ISPs. We performed p16 immunohistochemistry and high-risk HPV RNA in situ hybridization on 30 benign ISPs, 7 ISPs with dysplasia, 16 ISPs with carcinomatous transformation, and 7 non-keratinizing squamous cell carcinomas (SCCs) with inverted growth that were unassociated with ISP. Transcriptionally active HPV was not detected in any of the 52 ISPs including those that had undergone carcinomatous transformation, but it was detected in two of seven (29%) non-keratinizing SCCs that showed inverted growth. There was a strong correlation between high-risk HPV RNA in situ hybridization and p16 immunohistochemistry (97%; p < 0.01). These results indicate that transcriptionally active high-risk HPV does not play a common role in either the development of ISP or in its transformation into carcinoma.
Current data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of ...malignancy in nodules≥4 cm with benign cytology.
We performed a single-institution retrospective review of patients who underwent surgery from 07/2008–08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression.
Of 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1–0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7–1.4,p = 0.980, and OR:9.6,95%CI:0.9–107.8,p = 0.066, respectively).
Patients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.
•The overall risk of malignancy in cytologically benign thyroid nodules ≥4 cm was 5.3%.•Patients <55 years old have a 3.7-fold higher risk of malignancy than those ≥55.•Patients with ≥3 nodules measuring ≥4 cm had higher risk of malignancy.•Increasing nodule size and high-risk ultrasound were not associated with malignancy.•Treatment decisions should incorporate age for nodules ≥4 cm with benign cytology.
Although low-grade non-intestinal-type sinonasal adenocarcinoma (SNAC) is formally a diagnosis of exclusion defined by the absence of salivary or intestinal differentiation, most tumors in this ...category comprise a distinctive histologic group that are increasingly thought to derive from seromucinous glands. However, the molecular underpinnings of SNAC remain poorly understood, and it is unclear if diverse genetic alterations recently reported in isolated cases should delineate separate subgroups. This study aims to perform comprehensive evaluation of gene fusions and mutations and their histologic correlates in low-grade SNAC to clarify its pathogenesis and classification. We identified 18 non-intestinal-type SNAC that all displayed characteristic tubulopapillary architecture and low-grade cytology, although several cases had other unique histologic features and 3 showed intermixed high-grade areas. Among tumors stained with S100 protein, SOX10, and DOG1, 86% expressed at least one of these seromucinous markers. Of 17 cases with sufficient RNA or DNA available for analysis, likely oncogenic molecular alterations were identified in 76% of cases, most notably including CTNNB1 p.S33F mutations in 2 cases, concomitant BRAF p.V600E and AKT1 p.E17K mutations in 2 cases, and ETV6::NTRK3, PRKAR1A::MET, FN1::NRG1, and DNAJB1::PRKACA fusions in 1 case each. While tumors with most genetic alterations were histologically indistinguishable, cases with CTNNB1 mutations had intermixed squamoid morules and cases with BRAF and AKT1 mutations showed a myoepithelial cell population and prominent papillary to micropapillary architecture. Overall, these findings confirm previous reports of frequent seromucinous differentiation in low-grade SNAC. However, these tumors display striking molecular diversity with involvement of multiple kinase fusions, leading to frequent activation of signaling cascades including the MAPK pathway. While most genetic alterations are not associated with sufficiently distinctive histologic features to suggest separate classification, biphasic tumors with BRAF p.V600E mutations are more unique and may represent a distinctive subgroup.
While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of ...sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition. We identified sinonasal amoebiasis in 4 men, median age of 67 years (range: 37 to 71 y). All were immunocompromised, including 2 with chronic lymphocytic leukemia, 1 with human immunodeficiency virus, and 1 with human immunodeficiency virus and kidney transplant. Patients presented with nasal mucosal necrosis or polypoid masses, with facial ulceration in 1 patient and distant dermal nodules in another. Biopsies displayed extensive necrotic debris and inflammation. Although amoebic cysts were abundant in 3 cases, they were mistaken for yeast at frozen section in 1 case; 1 case showed only rare trophozoites that were not recognized on initial biopsy. Periodic acid Schiff and Grocott Methenamine Silver stains highlighted the organisms, and polymerase chain reaction confirmed Acanthamoeba species in 3 cases tested. 2 patients responded well to antiprotozoal medications, but 2 died of disease. Overall, sinonasal amoebiasis presents as a necroinflammatory process in patients immunocompromised for various reasons. Amoebae can mimic other organisms or be incredibly scarce, requiring active consideration to recognize amoebiasis and differentiate it from overlapping conditions like invasive fungal sinusitis, granulomatosis with polyangiitis, and natural killer/T-cell lymphoma. Because sinonasal amoebiasis is highly treatable when diagnosed promptly, pathologists play a critical role in the recognition of this rare necroinflammatory disease.
The designation “mucoepidermoid tumor” is a historic one used in reference to a form of mucoepidermoid carcinoma (MEC) that was believed to be benign. This bygone notion was based on the observation ...that the vast majority of MECs arising from the intraoral minor salivary glands behave in a benign fashion, particularly when they do not exhibit high grade features. There has been a recent move to partition the oral vault into the oral cavity proper and the oropharynx based on awareness that these compartments are distinct, and that similar tumor types arising from these compartments may behave in dramatically different ways (e.g, oral cavity squamous cell carcinoma vs oropharyngeal squamous cell carcinoma). The pathology databases from 3 large academic medical centers were searched for cases of MECs arising in the oropharynx. Relevant clinical and pathological information was collected from the medical records. Twenty-five cases were identified. They were from 18 females (72%) and 7 males (28%), ranging in age from 31 to 88 years (median, 61). Twenty-two (88%) were classified as low (n = 12) or intermediate (n = 10) grade, and 3 (12%) as high grade. Most arose from the base of tongue (n = 24), but one arose from the lateral pharyngeal wall. The median tumor size was 2.0 cm. Nineteen patients underwent neck node dissections. Of these, 13 (68%) had histologically documented lymph node metastases. MECs that lacked high grade features were almost as likely to metastasize as those with high grade features (50% vs 66%, Fisher exact = 1). Of 3 metastases tested, 2 harbored the MAML2 gene fusion. MECs arising from the base of tongue are associated with an alarmingly high rate of nodal metastases. This behavior cannot be predicted by histologic grading or MAML2 status. The propensity to metastasize may to some degree reflect the unique microenvironment of the oropharynx.
•Similar tumor types of the oral vault may behave very differently depending on whether they take origin from the oral cavity proper or the oropharynx•Mucoepidermoid carcinomas of the oropharynx are associated with an alarmingly high rate of nodal metastasis, a behavior that cannot be predicted by histologic grading•This propensity to metastasize may reflect the unique microenvironment of the oropharynx
Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its ...molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end. This overlap can cause diagnostic confusion, and it raises questions about the boundaries and definition of keratocystoma as an entity. This study seeks to utilize molecular tools to evaluate the pathogenesis of keratocystoma as well as its relationship with its histologic mimics. On the basis of targeted RNA sequencing (RNA-seq) results on a sentinel case, RUNX2 break-apart fluorescence in situ hybridization (FISH) was successfully performed on 4 cases diagnosed as keratocystoma, as well as 13 cases originally diagnosed as tumors that morphologically resemble keratocystoma: 6 primary squamous cell carcinomas, 3 metaplastic/dysplastic Warthin tumors, 2 atypical squamous cysts, 1 proliferating trichilemmal tumor, and 1 cystadenoma. RNA-seq and/or reverse transcriptase-PCR were attempted on all FISH-positive cases. Seven cases were positive for RUNX2 rearrangement, including 3 of 4 tumors originally called keratocystoma, 2 of 2 called atypical squamous cyst, 1 of 1 called proliferating trichilemmal tumor, and 1 of 6 called squamous cell carcinoma. RNA-seq and/or reverse transcriptase-PCR identified IRF2BP2::RUNX2 in 6 of 7 cases; for the remaining case, the partner remains unknown. The cases positive for RUNX2 rearrangement arose in the parotid glands of 4 females and 3 males, ranging from 8 to 63 years old (mean, 25.4 years; median, 15 years). The RUNX2 -rearranged cases had a consistent histologic appearance: variably sized cysts lined by keratinizing squamous epithelium, plus scattered irregular squamous nests, with essentially no cellular atypia or mitotic activity. The background was fibrotic, often with patchy chronic inflammation and/or giant cell reaction. One case originally called squamous cell carcinoma was virtually identical to the other cases, except for a single focus of small nerve invasion. The FISH-negative case that was originally called keratocystoma had focal cuboidal and mucinous epithelium, which was not found in any FISH-positive cases. The tumors with RUNX2 rearrangement were all treated with surgery only, and for the 5 patients with follow-up, there were no recurrences or metastases (1 to 120 months), even for the case with perineural invasion. Our findings solidify that keratocystoma is a cystic neoplastic entity, one which appears to consistently harbor RUNX2 rearrangements, particularly IRF2BP2::RUNX2 . Having a diagnostic genetic marker now allows for a complete understanding of this rare tumor. They arise in the parotid gland and affect a wide age range. Keratocystoma has a consistent morphologic appearance, which includes large squamous-lined cysts that mimic benign processes like metaplastic Warthin tumor and also small, irregular nests that mimic squamous cell carcinoma. Indeed, RUNX2 analysis has considerable promise for resolving these differential diagnoses. Given that one RUNX2 -rearranged tumor had focal perineural invasion, it is unclear whether that finding is within the spectrum of keratocystoma or whether it could represent malignant transformation. Most important, all RUNX2 -rearranged cases behaved in a benign manner.
Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (
n
...= 6). Patients were predominately female (
n
= 7) with a median age of 48 years (35–62 years). The most common primary location of the AdCC was head and neck (
n
= 6, among them parotid gland = 4), followed by lung (
n
= 2), breast (
n
= 1), and vulva (
n
= 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1–336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.
Clear cell carcinoma (CCC) is a low-grade malignancy that commonly arises in minor salivary glands of the oropharynx and other sites. EWSR1-ATF1 gene fusions seem to be specific for this salivary ...neoplasm. Testing for EWSR1-ATF1 has expanded the histologic spectrum of CCC. As one important example, many CCCs have a predominantly squamous phenotype with few clear cells, a finding that can cause confusion with squamous cell carcinoma (SqCC). P16 immunohistochemical staining to determine human papillomavirus (HPV) status has become standard practice for all oropharyngeal carcinomas showing squamous differentiation. The purpose of this study was to determine whether this practice could contribute to the difficulty in distinguishing CCC from p16-positive SqCC. The authors' surgical pathology archives were searched for cases of CCC. All cases were evaluated with p16 immunohistochemistry, high-risk HPV RNA in situ hybridization (ISH), and EWSR1 gene break-apart fluorescence ISH. Sixteen CCCs were identified. All harbored an EWSR1 rearrangement. Eleven patients were women and 5 were men. They ranged in age from 30 to 85 years (mean, 58 y). The CCCs arose in the oropharynx (tongue base or tonsil) (n=8, 50%), oral cavity (n=4, 25%), and nasopharynx (n=4, 25%). Each case demonstrated clear cells, but the proportion was highly variable (10% to 90%, mean 48%), with 7 of 16 cases having <50% clear cells. Submitted diagnoses included SqCC (n=3) and mucoepidermoid carcinoma (n=2). Of the 3 patients diagnosed with SqCC, 1 was scheduled to undergo chemoradiation, and 1 had already completed chemoradiation. All 16 CCCs demonstrated p16 staining, with the percentage of p16-positive cells ranging from ≥70% (n=2), 50% to 69% (n=3), and 10% to 49% (n=11). Staining was cytoplasmic and nuclear. All cases were negative for high-risk HPV by RNA ISH. CCCs regularly show squamous features, often lack prominent clear cell changes, frequently arise in the oropharynx, and invariably show p16 staining. These features may cause confusion with SqCC, particularly HPV-related oropharyngeal SqCC. P16 staining is not to be taken as unequivocal evidence of an HPV-related SqCC, even for carcinomas showing squamous differentiation and originating in the oropharynx. Failure to recognize this pitfall could result in overly aggressive treatment of a low-grade carcinoma.
Paraganglioma of the recurrent laryngeal nerve London, Nyall R.; Hopkins, Mark; Best, Simon R. ...
The Laryngoscope,
December 2020, 2020-12-00, 20201201, Letnik:
130, Številka:
12
Journal Article
Recenzirano
Paragangliomas of the head and neck are rare, and most frequently benign, slow growing, and nonsecretory. The most frequent locations these tumors arise in the head and neck include the carotid body, ...jugular bulb, vagus nerve, tympanic branch of the glossopharyngeal nerve, and sympathetic chain. Here we present, to our knowledge, the second reported case of paraganglioma of the recurrent laryngeal nerve. This case is unique given the patient presentation due to ipsilateral vocal fold paralysis, which has not previously been reported, lack of previous surgery, and demonstration of loss of succinate dehydrogenase iron‐sulfur subunit B expression. Laryngoscope, 2019
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