Background Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including ...decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. Methods We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. Results There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs 71%; P < .001) and had a younger median age (43 vs 47 years; P = .03), a lesser incidence of CNM (35% vs 52.4%; P < .001), and a greater incidence of pT1a (40% vs 25%; P < .001) and pT1b (38% vs 29%; P < .001) tumors. Multivariate analysis showed that the presence of CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38–0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9–11% risk of CNM with pT1a tumors. Conclusion Female patients of all ages with CLT and small PTCs have the least incidence of CNM.
Summary Recent advances in the treatment of pulmonary adenocarcinoma have increased the need for accurate typing of non–small cell carcinomas. Immunohistochemistry for thyroid transcription factor-1 ...is widely used in the diagnosis of pulmonary adenocarcinomas because it marks approximately 75% of lung adenocarcinomas and is negative in most squamous cell carcinomas and adenocarcinomas of other organs. Napsin A is an aspartic proteinase involved in the maturation of surfactant protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar macrophages and is a putative marker for pulmonary adenocarcinomas. We performed immunohistochemistry for napsin A and thyroid transcription factor-1 using tissue microarrays of 95 adenocarcinomas, 48 squamous cell carcinomas, 6 neuroendocrine tumors of the lung, as well as 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas, 38 malignant mesotheliomas, 118 renal cell carcinomas, and 81 thyroid tumors. The tissue microarrays also included 15 different benign tissues. Pulmonary adenocarcinomas were napsin A positive in 79 (83%) of 95 cases compared with 69 (73%) of 95 cases that were thyroid transcription factor-1 positive. There were 13 napsin A–positive/thyroid transcription factor-1–negative and 2 thyroid transcription factor-1–positive/napsin A–negative tumors, increasing the number of cases that were positive with at least one of the markers to 81 (85%) of 95. The limited number of neuroendocrine tumors tested was napsin A negative. All squamous cell carcinomas, adenocarcinomas of the colon, pancreas and breast, and mesotheliomas were negative for both markers. Of the renal tumors, napsin A was positive in most of papillary renal cell carcinomas (79%), about one third (34%) of clear cell renal cell carcinomas, and in a single case of chromophobe renal cell carcinoma (3%). In the thyroid, only 2 cases of papillary thyroid carcinoma (5%), both with tall cell morphology, were positive for napsin A, whereas all other papillary and follicular carcinomas were negative. As expected, all renal tumors were thyroid transcription factor-1 negative, and all thyroid tumors, except for one papillary carcinoma, were thyroid transcription factor-1 positive. Napsin A is a sensitive marker for pulmonary adenocarcinoma and is also expressed in a subset of renal cell carcinomas, particularly of the papillary type, as well as in rare cases of papillary thyroid carcinomas. The combined use of napsin A and thyroid transcription factor-1 results in improved sensitivity and specificity for identifying pulmonary adenocarcinoma in primary lung tumors and in a metastatic setting.
Biphenotypic sinonasal sarcoma (BSNS) is a recently recognized low-grade sarcoma that exhibits both neural and myogenic differentiation. This unique dual phenotype stems from recurrent rearrangements ...in PAX3 , a transcription factor that promotes commitment along both lineages. While identification of PAX3 rearrangements by fluorescence in situ hybridization (FISH) can confirm a BSNS diagnosis, this assay is not widely available. This study evaluates whether an expanded immunohistochemical panel can facilitate recognition of BSNS without molecular analysis. Eleven cases of BSNS were identified from the surgical pathology archives of two academic medical centers. In 8 cases, the diagnosis was confirmed by FISH using custom probes for PAX3. In 3 cases FISH failed but histologic and immunophenotypic findings were diagnostic for BSNS. All 11 BSNS (100%) were at least focally positive for S100 as well as calponin and/or smooth muscle actin. In addition, 10 of 11 (91%) expressed nuclear β-catenin, 8 of 10 (80%) expressed factor XIIIa, 4 of 11 (36%) expressed desmin, and 3 of 10 (30%) expressed myogenin. All 11 tumors were negative for SOX10. While no single marker resolves immunohistochemical overlap between BSNS and its histologic mimickers such as nerve sheath tumors, an extended immunohistochemical panel that includes β-catenin and SOX10 helps to support the diagnosis of BSNS without the need for gene rearrangement studies.
Summary Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely ...specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.
Summary Anaplastic thyroid carcinoma can be difficult to diagnose because it does not show thyroid differentiation morphologically or immunohistochemically. Depending on the histologic variant, ...anaplastic thyroid carcinoma may be confused with sarcoma or squamous cell carcinoma of the head and neck. PAX8 is a transcription factor expressed in normal and neoplastic thyroid follicular epithelium and only a few other tissues. This restricted expression suggests that PAX8 staining could be useful when dealing with spindled or squamoid tumors of the neck. The purposes of this study were to determine the frequency of PAX8 staining in anaplastic thyroid carcinoma and to evaluate PAX8 immunohistochemistry as a means of distinguishing its squamoid variant from head and neck squamous cell carcinoma. PAX8 immunohistochemical staining was performed on 34 anaplastic thyroid carcinomas and 118 head and neck squamous cell carcinomas. PAX8 staining was present in 26 (76%) anaplastic thyroid carcinomas including 16 (100%) of 16 squamoid variants, 7 (58%) of 12 giant cell/pleomorphic variants, and 3 (50%) of 6 spindled variants. All head and neck squamous cell carcinomas were negative for PAX8. PAX8 expression is often retained in anaplastic thyroid carcinomas including the squamoid variant, but it is not expressed in head and neck squamous cancers. PAX8 staining is an excellent marker for carcinomas of follicular epithelial origin, including those carcinomas that are undifferentiated in other respects. The tissue specificity of PAX8 expression may be useful in resolving the differential diagnosis of anaplastic thyroid carcinoma such as the distinction between its squamoid variant and squamous cell carcinoma of the head and neck.
Abstract Oropharyngeal squamous cell carcinoma caused by high-risk types of human papillomavirus (HPV) is now a well-recognized tumor entity whose incidence is on the rise. Most HPV-related ...oropharyngeal squamous cell carcinomas have a distinct histomorphology, and most patients fit a typical clinical profile. Importantly, HPV-related oropharyngeal carcinoma patients overall have significantly improved outcomes when compared to their HPV-negative counterparts, and the differences in tumor biology may soon lead to modifications in how they are treated. While high-risk HPV can be detected in a significant minority of head and neck squamous cell carcinomas across anatomic subsites in the head and neck, it has become clear in recent years that the biologically and clinically favorable features are limited to tumors that harbor transcriptionally active, high-risk HPV, something that occurs predominantly (but certainly not exclusively) in the oropharynx. It is now acknowledged that detecting transcriptionally active, high-risk HPV is a necessity in routine clinical practice, but there is considerable confusion among pathologists and clinicians alike about the subsites and settings in which HPV testing should be performed. Compounding this lack of clarity is the fact that there are multiple HPV testing options available, but currently there is no clear consensus on which test or combination of tests is optimal for routine diagnostic use. This review serves as an update for practicing pathologists on the current status of HPV (and surrogate marker) testing in head and neck cancers.
Abstract Surgical pathology of the sinonasal region (i.e., nasal cavity and the paranasal sinuses) is notoriously difficult, due in part to the remarkable diversity of neoplasms that may be ...encountered in this area. In addition, a number of neoplasms have been only recently described in the sinonasal tract, further compounding the difficulty for pathologists who are not yet familiar with them. This manuscript will review the clinicopathologic features of some of the recently described sinonasal tumor types: NUT midline carcinoma, HPV-related carcinoma with adenoid cystic-like features, SMARCB1 (INI-1) deficient sinonasal carcinoma, biphenotypic sinonasal sarcoma, and adamantinoma-like Ewing family tumor.
Summary Uroplakins are markers of terminally differentiated urothelium. Uroplakin II (UPII) is a newly described sensitive marker for urothelial carcinoma (UC). The expression profile of UPII in ...different types of UC and its utility in the diagnostic setting are needed. We evaluated UPII expression in bladder tissue microarrays, including urothelial neoplasm of low malignant potential (n = 8), low-grade papillary UC (n = 72), noninvasive high-grade papillary UC (n = 77), UC in situ (n = 27), and invasive high-grade UC (INVUC) (n = 122). UPII expression in 52 breast carcinomas and 38 high-grade prostate adenocarcinomas was also assessed. UPII expression was compared with GATA binding protein 3 (GATA3) and estrogen receptor for its role in facilitating the differential diagnosis of the above 3 types of malignancy. UPII labeling was seen in 83.0% of UC overall, including 95.7% of noninvasive UC and 65.6% of INVUC. UPII labeling was not found in any breast and prostate carcinomas. In comparison, GATA3 labeling was seen in 91.6% of all UCs, including 96.4% of noninvasive UCs and 85.1% of INVUC, with stronger intensity and extent compared with UPII ( P < .005). GATA3 labeled 2 (5%) of 38 high-grade prostate adenocarcinoma. Estrogen receptor nuclear labeling was seen in 13.0% of UCs and 12.5% of prostate carcinomas. UPII was highly specific (100%) but only moderately sensitive for UC and can therefore be a potentially useful marker to identify urothelial lineage and help distinguish UC from prostate cancer or, in conjunction with GATA3, from metastatic breast cancer.
Summary Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a ...form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.
Introduction Lymphoepithelial carcinoma of the salivary gland is an extremely rare neoplasm and is challenging to diagnose by fine needle aspiration (FNA). There are rare reports on the ...cytopathologic features of lymphoepithelial carcinoma, which may be mistaken for other high-grade salivary gland neoplasm or a metastasis to the salivary gland. Materials and methods A retrospective review was undertaken of 7 cases of lymphoepithelial carcinoma of the parotid diagnosed on FNA with histologic confirmation from 4 major medical centers. Results Cytomorphologic features of lymphoepithelial carcinoma include smears with moderate cellularity displaying a rich nonneoplastic population of lymphoplasmacytic cells admixed with tissue fragments of high grade, malignant undifferentiated epithelial cells with high nuclear to cytoplasm ratio, hyperchromasia, prominent nucleoli, and scant to abundant, indistinct cytoplasm. Discussion Diagnostic pitfalls of lymphoepithelial carcinoma include metastatic squamous cell carcinoma, metastatic nasopharyngeal carcinoma, and other high grade primary salivary gland neoplasms. Recognizing this lesion may help guide clinicians to perform additional imaging studies to exclude a primary from other sites.
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