Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience.

Purpose: This series reports long-term clinical outcomes of patients with salivary duct carcinoma (SDC), which is associated with a poor prognosis. Methods and Materials: Eighty-nine patients with SDC were treated with curative intent from February 5, 1971, through September 15, 2018. Kaplan-Meier and competing risk analyses were used to estimate locoregional control, distant metastasis-free survival (DMFS), progression-free survival, and overall survival (OS). Cox regression analyses of disease and treatment characteristics were performed to discover predictors of locoregional control, DMFS, and OS. Results: Median follow-up was 44.1 months (range, 0.23-356.67). The median age at diagnosis was 66 years (interquartile range, 57-75). Curative surgery followed by adjuvant radiation therapy was performed in 73 patients (82%). Chemotherapy was delivered in 26 patients (29.2%). The 5-year local recurrence and distant metastasis rates were 27% and 44%, respectively, with death as a competing risk. Distant metastasis was associated with lymph node-positive disease (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.38-7.23; P = .006), stage IV disease (HR, 4.78; 95% CI, 1.14-20.11; P = .033), perineural invasion (HR, 4.56; 95% CI, 1.74-11.97; P = .002), and positive margins (HR, 9.06; 95% CI, 3.88-21.14; P < .001). Median OS was 4.84 years (95% CI, 3.54-7.02). The 5-year OS was 42%. Reduced OS was associated with lymphovascular space invasion (HR, 3.49; 95% CI, 1.2-10.1; P = .022), perineural invasion (HR, 2.05; 95% CI, 1.06-3.97; P = .033), positive margins (HR, 2.7; 95% CI, 1.3-5.6; P = .011), N2 disease (HR, 1.88; 95% CI, 1.03-3.43; P = .04), and N3 disease (HR, 11.76; 95% CI, 3.19-43.3; P < .001). Conclusions: In this single-institution, multicenter retrospective study, the 5-year survival was 42% in patients with SDC. Lymphovascular space invasion, lymph node involvement, and higher staging at diagnosis were associated with lower DMFS and OS.

Imaging Patients with Kidney Failure.

The approach to imaging a patient with kidney failure continues to evolve. Overstatement of the risk of iodinated contrast material-induced (ie, contrast-induced) acute kidney injury and new guidelines for administration of gadolinium-based contrast media affect screening and the choice of contrast material. Treatment of kidney failure requires dialysis or a kidney transplant. Pretransplant imaging includes assessment for the feasibility of performing a transplant and evaluation for underlying malignancy and peripheral vascular disease. Patients with kidney failure are at high risk for renal cell carcinoma. Subtypes that occur exclusively or more commonly in patients with kidney failure, such as acquired cystic kidney disease, renal cell carcinoma, and clear cell papillary renal cell carcinoma, have specific clinical-pathologic characteristics, with indolent behavior. Performing US for dialysis planning increases the success of placement of an arteriovenous fistula, while postoperative US evaluation is essential in assessment of access dysfunction. Systemic manifestations in patients with kidney failure are multifactorial and may relate to the underlying cause of renal failure or may be secondary to treatment effects. Disturbances in mineral and bone metabolism and soft-tissue and vascular calcifications are seen in patients with chronic kidney disease and mineral bone disorder. Neurologic and cardiothoracic complications are also common. The authors provide a comprehensive overview of imaging considerations for patients with kidney failure, including the appropriate use of CT, MRI, and US with their respective contrast agents; the use of imaging in transplant workup and dialysis assessment; and the common renal and extrarenal manifestations of kidney failure. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Complete response in Patients With Lung-Only Metastatic Prostate Cancer: Outcome Analysis.

Lung-only metastatic prostate cancer can be seen in 4.6% of patients and historically patients with visceral metastastic disease are considered high risk. In order to determine survival outcomes in this patient population, we conducted a restrospective review of patients with metastatic hormone sensitive prostate cancer with lung-only metastases. In this single institution review, 10 patients were identified with 8 achieving a complete response and 2 achieving a partial response when treated with androgen deprevation therapy (ADT) with or without metastastetomy. The median progression free survival was 64.4 months with 8 of these patients (80%) with ongoing complete response at time of follow-up. Lung-only metastases may serve as a good prognostic characteristic which will allow the clinician to treat with ADT alone with or without surgery to minimize treatment realted toxicity and still offer the ability to achieve a complete response with prolonged survival.

Fat Necrosis Mimicking Renal Cell Carcinoma Recurrence Following Cryotherapy, Partial Nephrectomy, and Nephrectomy.

OBJECTIVE: To present our experience with three patients surgically treated for suspected recurrent renal cell carcinoma whose final pathology was consistent with tumefactive fat necrosis. METHODS: Three patients underwent definitive therapy for biopsy proven renal cell carcinoma (cryoablation, partial nephrectomy, and nephrectomy) and later demonstrated evidence of recurrent renal cell carcinoma on follow up imaging. All three patients underwent surgical resection of the suspected recurrences with final pathology consistent with tumefactive fat necrosis. RESULTS: The three patients were 60, 74, and 39-years old, respectively. The previous definitive therapies for renal cell carcinoma were percutaneous ablation, RAPN, and nephrectomy. Each patient had previous surgical pathology that confirmed prior renal cell carcinoma. Signs of recurrence on diagnostic imaging occurred 2 years, 23 months, and 8 months post-definitive therapy. CONCLUSION: In patients with a history of renal cell carcinoma, consideration of fat necrosis should be taken into account upon seeing imaging concerning for tumor recurrence. Continued analysis of cases with such a diagnosis will be beneficial in recognizing this possibility to avoid unnecessary surgery or therapy when possible.

Association of Ancillary Pathology Findings in Non-neoplastic Renal Parenchyma and Renal Outcomes of Robotic-Assisted Partial Nephrectomy.

Background: To evaluate robotic-assisted partial nephrectomy (RAPN) renal outcomes associated with ancillary pathology findings in non-neoplastic renal parenchymal tissue. Methods: Tissue samples from 378 RAPNs were analyzed for glomerular disease (GD), vascular disease (VD), and tubulointerstitial disease (TD). One hundred and fifty-two patients were excluded due to insufficient non-neoplastic tissue for analysis and 4 patients were excluded due to calyceal diverticulum. Non-neoplastic tissue was evaluated for GD (negative, moderate, or global), VD (absent, mild, moderate, or severe), and TD (present or absent). Associations of ancillary pathology factors with patient characteristics were explored using the non-parametric Kendall tau-test and propensity score adjusted longitudinal mixed effects regression models were used to evaluate associations of these pathology factors with changes in estimated glomerular filtration rate (eGFR) following RAPN. Results: One hundred and fifty-three (68.9%) patients had hypertension and 50 (22.5%) patients had diabetes. The majority of patients did not have any GD (N = 158, 71.2%) or TD (N = 186, 83.8%) while 129 (58.1%) had VD. VD was categorized as absent (N = 93, 41.9%), mild (N = 45, 20.3%), moderate (N = 76, 34.2%), and severe (N = 8, 6.8%). Older age (P = 0.018), hypertension (P < 0.001), and high grade MAP score (P = 0.047) were associated with a higher number of ancillary pathology factors. High grade MAP score (P = 0.03, P = 0.002) and hypertension (P = 0.02, P < 0.001) were individually associated with GD severity and VD severity, respectively. Older age was also individually associated with VD severity (P = 0.002) and hypertension was associated with TD (P = 0.04). Moderate-to-severe VD was associated with a worse change in eGFR from pre-RAPN to 1-month post-RAPN compared to those with mild or no VD (difference in mean change, -3.4 ml/kg/1.73m2; 95% CI, -6.6 to -0.2 ml/kg/1.73m2; P = 0.036). Conclusions: Moderate-to-severe VD in non-neoplastic renal parenchyma is associated with post-operative changes in eGFR. Older age, hypertension, and high grade MAP scores are associated with the number of ancillary pathologies observed in RAPN specimens.

Case report expanding the germline AXIN2- related phenotype to include olfactory neuroblastoma and gastric adenoma.

BACKGROUND: Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant. CASE PRESENTATION: The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed. CONCLUSIONS: This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.

Thoracoabdominal resection of giant malignant esophageal solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm. It usually originates from the parietal pleura. SFT originating from the esophagus is exceedingly rare and even more so as a malignancy. We report a 57-year-old patient with a malignant 18 cm SFT of the esophagus that was treated with esophagectomy through a left thoracoabdominal incision. We discuss his surgical and oncologic management.

Case of aggressive metastatic follicular variant papillary thyroid carcinoma with BRAF K601E and BCORL1 mutations.

BCL6 corepressor like-1 (BCORL1) mutation has rarely been described in thyroid cancer or in association with BRAF mutations in any malignancy. However, we report a 49-year-old woman who had aggressive follicular variant papillary thyroid carcinoma (FV-PTC) with both the BRAF K601E and BCORL1 mutations. The patient underwent a total thyroidectomy for a 3.6 cm right thyroid nodule and a smaller lesion in the left lobe in 2007; both were FV-PTCs with no lymphovascular invasion or metastases. In 2015, a positron emission tomography-CT scan showed a small defect in the left posterior lateral fifth rib with mild increased hypermetabolic activity with standardised uptake value of 3.9 and another lesion in the right hip at the junction of the femoral neck and trochanter. Tumour biopsy and genetic analysis revealed an uncommon BRAF K601E and a rare BCORL1 mutation. While rare, we report a case of aggressive FV-PTC with both the BRAF K601E and BCORL1 mutations.

Subaortic Membrane Papillary Fibroelastoma.

A 61-year-old male presented for an annual exam and received a transthoracic echocardiogram (TTE) which revealed a mobile mass arising from a subaortic membrane. Further investigations with a transesophageal echocardiogram (TEE) and cardiac computerized tomography angiography (CTA) confirmed the presence of a mobile 9 mm × 3 mm mass on a subaortic membrane. Cardiothoracic surgery was performed with an open operation removing the mass and subaortic membrane. Upon visual inspection, the mass was likened to a sea anemone and immunohistochemical staining performed pathologically confirmed the diagnosis of cardiac papillary fibroelastoma. This case represents the first reported example of a cardiac papillary fibroelastoma (PFE) arising from a subaortic membrane. Although PFEs are benign cardiac tumors, proper identification and consideration for excision of these lesions may be indicated to prevent thromboembolic complications.

Primary synovial sarcoma of the kidney-A case report and literature review.

Primary synovial sarcoma of the kidney is a very rare spindle cell neoplasm that occasionally displays epithelial differentiation. It occurs between 15-60 years of age with a mean of 35 years and a slight male predilection. Most of synovial sarcomas appear as relatively nonspecific soft tissue masses involving the kidney. This rare entity has some overlapping morphologic and immunohistochemical characteristics with other more common renal spindle cell neoplasms. Molecular tools add valuable diagnostic confirmation. We report a 56 year old male who presented to the emergency department with hematuria and abdominal pain. He had an abdominal CT-scan which showed a 6.6 cm enhancing right renal mass. Morphologic and immunohistochemical studies were directed towards synovial sarcoma with confirmation by SYT-SSX gene fusion using RT-PCR molecular technique. We reviewed the literature on the epidemiologic, histologic spectrum, immunophenotypic, clinical significance and prognosis and therapy.

Updates on Immunohistochemical and Molecular Markers in Selected Head and Neck Diagnostic Problems.

CONTEXT: - The head and neck regions have complex anatomic structures. They are not exempted from the rare occurrences of highly unusual, diagnostically challenging malignant neoplasms and mimickers. OBJECTIVE: - To review and update the utility of immunohistochemistry and molecular biomarkers and to pursue diagnostic accuracy on selected rare neoplasms, especially some poorly differentiated malignancies. DATA SOURCES: - Personal experience and information from the literature. CONCLUSIONS: - Head and neck tumors include neoplasms originating from heterogeneous tissue. Using the selected clinical cases, this review illustrates a continuous development of emerging molecular-genetic techniques to assist in the interpretation of uncommon, often poorly differentiated, highly malignant neoplasms. The diagnostic results are appropriately transmitted to the oncologists, radiation oncologists, and surgeons to create a coordinated plan of care for patients with these unusual disorders affecting the head and neck.

Relapse Rates With Surgery Alone in Human Papillomavirus-Related Intermediate- and High-Risk Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review.

PURPOSE: To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-human papillomavirus (HPV) and pre-transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+ oropharyngeal squamous cell cancer patients undergoing TOS. METHODS AND MATERIALS: A multi-institutional retrospective review of intermediate- and high-risk HPV+ oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or ≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. RESULTS: Median follow-up was 42.9 months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. CONCLUSIONS: Risk category was associated with clinically significant relapse rates after TOS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer.

Primary Hepatic Neuroendocrine Tumor with Unusual Thyroid Follicular-Like Morphologic Characteristics.

We describe a primary hepatic neuroendocrine tumor of a 57-year-old Thai woman who presented in 2004 with a suspicious mass in the left hepatic lobe. She underwent left hepatectomy for the 10.5-cm mass, called intermediate grade neuroendocrine carcinoma of unknown origin, likely metastatic. The tumor recurred in 2007, then called recurrent primary hepatic neuroendocrine tumor (PHNET), and the patient underwent liver transplant. Because of similarity between the neuroendocrine tumor and a thyroid tumor-specifically, follicular-like characteristics-immunohistochemical stains for thyroglobulin, TTF1, and calcitonin were performed. However, all were negative. All imaging studies revealed no evidence of a primary lesion other than the liver mass. In 2008, the patient's liver transplant failed because of ischemic cholangiopathy, and she underwent a second liver transplant. Seven years later, in 2015, she presented with metastatic neuroendocrine tumor of intermediate grade to the lung, consistent with metastatic PHNET. She underwent left upper-lobe wedge resection to remove the tumor. The patient is alive with no evidence of disease at 13 years after initial diagnosis. This rare variant of PHNET had thyroid-like morphologic characteristics but there is no evidence of primary thyroid tumor or thyroid markers in the primary and recurrent hepatic tumors and lung metastasis.

Invasive ductal carcinoma with in situ pattern: how to avoid this diagnostic pitfall?

Although the microscopic features of invasion are usually readily recognized, occasionally invasive ductal carcinoma may mimic the pattern of comedo ductal carcinoma in situ (DCIS) by forming large cellular nests with circumscribed borders, but lacking a definitive myoepithelial cell layer. In these cases, the histologic pattern may appear deceptively noninvasive and the absence of a myoepithelial layer can be easily overlooked. We prospectively examined 10 cases of high grade DCIS. P63, smooth muscle actin, muscle specific actin and calponin immunohistochemical stains were used to identify the presence of myoepithelial cells. In our study, 20% of apparent high grade DCIS cases did not exhibit a myoepithelial layer surrounding large, solid nests with comedo necrosis. Since invasion is defined by the absence of a myoepithelial layer, these results suggest that a DCIS-like pattern may actually represent invasive disease in some cases. Immunohistochemical studies may be essential in making this distinction and in avoiding the potential diagnostic pitfall.

Plectin-1 as a Biomarker of Malignant Progression in Intraductal Papillary Mucinous Neoplasms: A Multicenter Study.

OBJECTIVE: This study aimed to evaluate Plectin-1 expression as a biomarker of malignant risk for intraductal papillary mucinous neoplasms (IPMNs). METHODS: Plectin-1 immunohistochemistry (IHC) was performed retrospectively on surgical (n = 71) and cytological (n = 33) specimens from Mayo Clinic Jacksonville and UCLA Medical Center, including IPMNs with low-grade dysplasia, high-grade dysplasia (HGD), or an associated invasive adenocarcinoma. RESULTS: Plectin-1 expression was increased in invasive adenocarcinoma compared with adjacent in situ IPMN (P = 0.005), as well as the in situ HGD component of IPMNs with invasive cancer compared with HGD of IPMNs without invasive cancer (P = 0.02). Plectin IHC discriminated IPMNs with invasive adenocarcinoma from noninvasive IPMN (area under the curve [AUC] of 0.79, 75% sensitivity, and 85% specificity) but was insufficient for discriminating HGD IPMN from low-grade dysplasia IPMNs in surgical resections (AUC of 0.67, 56% sensitivity, and 64% specificity) or fine-needle aspiration specimens (AUC of 0.45). CONCLUSIONS: Although Plectin-1 IHC has insufficient accuracy to be used as a definitive biomarker for malignant risk in the evaluation of IPMN biopsy or cytological specimens, increased Plectin-1 expression observed in both invasive cancer and in situ HGD of malignant IPMNs suggests that it might be successfully leveraged as a cyst fluid biomarker or molecular imaging target.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: more aggressive than previously reported.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a rare traditionally "low-grade" tumor that predominantly occurs in women. Approximately 50 cases have been reported in the literature. It arises in a background of Hashimoto thyroiditis and is characterized by nests of epidermoid and mucin-secreting cells located within an eosinophil-rich sclerotic stroma. Herein, we outline the clinicopathological and immunohistochemical characteristics of 6 cases of thyroid SMECE. All tumors were detected in women (age, 36-89 years; average, 59 years), and all patients underwent total thyroidectomies. Clinicopathological findings included extensive tumor invasion into the adjacent soft tissues, trachea, pharynx, and esophagus. Of 6 specimens, 5 had positive surgical margins. Cervical lymph node metastases were seen in 4, and distant metastases were in 3 patients. Immunohistochemically, all tumors were positive for CK19, galectin 3, and p63 and negative for calcitonin, calponin, S-100, and smooth muscle actin. Interestingly, 2 tumors also showed faint focal staining for thyroglobulin, and 2 others had focal positivity for thyroid transcription factor 1. Together, galectin 3 and CK19 expression supported the malignancy of these lesions, and p63 expression raised the possibility that these tumors originated from the ultimobranchial body. In summary, SMECE tumors in our series exhibit a clear female predominance with aggressive behavior and appear to arise from pluripotent solid cell nests. A correct diagnosis is crucial to providing SMECE patients with the appropriate treatment options, and we recommend a closer follow-up schedule than previously considered.

Diagnostic utility of E-cadherin and P120 catenin cocktail immunostain in distinguishing DCIS from LCIS.

BACKGROUND: Breast carcinoma in situ (CIS) is classified into ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). DCIS is treated with surgical excision while LCIS can be clinically followed with or without hormonal treatment. Thus, it is critical to distinguish DCIS from LCIS. Immunohistochemical (IHC) staining for E-cadherin is routinely used to differentiate DCIS from LCIS in diagnostically challenging cases. Circumferential diffuse membranous staining of E-cadherin is the typical pattern in DCIS, whereas LCIS lacks or shows decreased E-cadherin expression. Recent studies have shown that DCIS has membranous staining of P120 catenin and LCIS has diffuse cytoplasmic staining of P120 catenin. We developed a cocktail composed of E-cadherin and P120 catenin primary antibodies so that only one slide is needed for the double immunostains. DESIGNS: Twenty-seven blocks of formalin-fixed paraffin-embedded tissue from 26 cases of DCIS or LCIS were retrieved from the archives of Houston Methodist Hospital. Four consecutive sections from the same blocks were used for H&E and immunohistochemical (IHC) stains. The E-cadherin antibody was a rabbit polyclonal antibody and the P120 catenin antibody was a mouse monoclonal antibody. The E-cadherin primary antibody was detected using a secondary antibody raised against rabbit antibody and was visualized with a brown color. The P120 catenin primary antibody was detected using a secondary antibody raised against mouse antibody and was visualized with a red color. RESULTS: Using individual antibodies, 15 of 15 DCIS lesions had diffuse circumferential membranous E-cadherin staining (brown stain) or P120 catenin staining (red stain). All 12 LCIS cases showed cytoplasmic P120 red staining or loss of E-cadherin staining when the single P120 catenin or E-cadherin antibody was used. When stained with the antibody cocktail, all 15 DCIS samples showed diffuse red and brown membranous staining without cytoplasmic stain; all 12 LCIS samples showed diffuse cytoplasmic red staining for P120 catenin but no membranous staining for E-cadherin. CONCLUSIONS: 1. This antibody cocktail can be applied in daily practice on paraffin-embedded tissue and is especially useful in small biopsies with small foci of CIS lesions. 2. Immunohistochemical staining with the antibody cocktail showed 100% concordance with the traditional single antibody immunostaining using either E-cadherin or P120 catenin antibody. 3. Our antibody cocktail includes E-cadherin as a positive membranous stain for DCIS and P120 catenin as a positive cytoplasmic stain for LCIS, which may enhance accuracy and confidence in the differential diagnoses.