Sebaceous Carcinoma of the Middle Ear: A Case Report.

Here we present the first case of sebaceous carcinoma of the middle ear. We discuss the treatment course and post treatment results after 11 years of follow up. We further summarize the available literature of sebaceous carcinoma of the temporal bone, which prior to this case was exclusively limited to the external auditory canal. Laryngoscope, 2024.

Validation and interpretation of Pan-TRK immunohistochemistry: a practical approach and challenges with interpretation.

OBJECTIVES: Actionable, solid tumor activating neurotrophic receptor tyrosine kinase (NTRK) fusions are best detected via nucleic acid-based assays, while Pan-TRK immunohistochemistry (IHC) serves as a reasonable screening modality. We describe a practical and cost-effective approach to validate pan-TRK and discuss challenges that may be encountered. METHODS: Pan-TRK Clone EPR17341 was validated in accordance with the 2014 consensus statements set forth by the College of American Pathologists. Confirmation of IHC results were guided by the European Society of Medical Oncology recommendations for standard methods to detect NTRK fusions. RESULTS: Within 36 samples, ETV6-NTRK3 (n = 8) and TPM4-NTRK3 (n = 1) fusions were confirmed. ETV6-NTRK3 fusion positive cases revealed cytoplasmic and nuclear staining. A TPM4-NTRK3 fusion positive high grade malignant peripheral nerve sheath tumor revealed diffuse cytoplasmic staining. A high grade ovarian serous carcinoma revealed focal punctate staining and revealed a non-actionable NTRK1 truncation at intron 2. Diffuse cytoplasmic staining was observed in a case of fusion-negative polymorphous adenocarcinoma. Wild-type expression of TRK in pulmonary meningothelial-like nodules was discovered following a false-positive IHC interpretation. CONCLUSION: Pan-TRK IHC shows some utility as a diagnostic and surrogate marker for NTRK screening however, physiologic or non-specific expression may lead to false-positive results.

Ameloblastic Carcinoma of the Maxilla: A Rare Case Report and Review of Literature from 1948 to 2021.

Ameloblastic carcinoma is a rare malignant neoplasm arising from the odontogenic epithelium. Ameloblastic carcinoma commonly occurs de novo affecting the posterior segments of the mandible. Presently, only less than 100 cases have been reported arising from the maxilla. We report a unique case of maxillary ameloblastic carcinoma in a 68-year-old male with a 5.6 cm positron emission tomography (PET) avid left maxillary sinus mass. The patient underwent a left maxillectomy which revealed hyperchromatic and pleomorphic tumor cells arranged in a nested and trabecular architecture. The tumor cells showed distinct peripheral palisading with reverse polarization. Areas of bone destruction, necrosis, lymphovascular and perineural invasions, as well as atypical mitoses, were identified. Immunohistochemically, the tumor cells were positive for keratin cocktail (AE1/AE3 and CAM 5.2), keratin 19, p40, and weakly positive for MDM2, while negative for calretinin. Molecular analysis revealed wild-type BRAF; however, alterations in CDKN2A/B, MTAP, RB1, SMARCA4, STK11, FGF12, SETD2, and TP53 were present. This histopathologic and molecular profile supported the diagnosis of ameloblastic carcinoma. There has been no evidence of disease recurrence or metastasis eleven months after the initial diagnosis.

Pituitary carcinoma: A cytopathologic dilemma when metastatic to cervical lymph nodes.

Pituitary carcinomas are rare tumors defined by distant metastasis or cerebrospinal spread. The morphologic features are poorly characterized because only a handful of reports have been described by fine-needle aspiration cytology. We present a case of pituitary carcinoma diagnosed in a 64-year-old male and highlight this rare entity's key cytomorphologic features and differential diagnosis.

NR4A3 fluorescence in situ hybridization analysis in cytologic and surgical specimens of acinic cell carcinoma.

Acinic cell carcinoma (AciCC) may pose a diagnostic challenge, particularly on small biopsies and fine needle aspiration (FNA) because of its variable histology including potential high-grade transformation and its mimickers. Immunoreactivity with circumferential membranous staining for DOG1 can support the diagnosis of AciCC but is not entirely specific. A novel rearrangement t(4;9)(q13;q31) leading to up-regulation of nuclear receptor subfamily 4 group A member 3 (NR4A3) has been described in AciCC, is potentially detectable by fluorescence in situ hybridization (FISH) and may be useful in the evaluation for AciCC. Using NR4A3 Dual Color Break Apart Probe (ZytoVision, Germany) FISH was performed on AciCCs from 3 large academic institutions. NR4A3 rearrangement was defined as positive signal patterns in 15% of tissue interphase nuclei. Fifty-two AciCCs including 47 resections and 5 FNAs (including 5 paired FNA/resections) were analyzed. Five non-AciCC salivary gland tumors and 2 sialadenitis cases were used as controls. Eight AciCCs (15%; 8/52) failed FISH testing. FISH was positive in 23 AciCCs (sensitivity 59%, 23/39) with 100% concordance between 5 matched resection/FNAs (3 were positive for FISH and 2 were negative). FISH was negative in all non-AciCCs (specificity: 100%, 0/7). NR4A3 FISH has a sensitivity of 59% and specificity of 100% in detecting AciCC, which suggests that NR4A3 rearrangement-driven up-regulation is a recurrent, specific oncogenic event in AciCC, consistent with prior results. Hundred percent concordance between matched FNA/resection samples validates its potential utility on cytology samples.

A 73-Year-Old Woman With Progressive Shortness of Breath and Right-Sided Hemithorax Opacity.

CASE PRESENTATION: A 73-year-old frail woman presented with 3 months of progressively worsening exertional dyspnea, mild cough with white mucus, voice changes, and few episodes of dysphagia. She denied weight loss, night sweats, chest pain, or hemoptysis. Medical history was significant for hypertension, remote 30 years of tobacco use, and regular alcohol use. She had neither asbestos nor occupational exposure. She had no family history of malignancy.

Long-Term Maintenance of Acinar Cells in Human Submandibular Glands After Radiation Therapy.

PURPOSE: In a combined retrospective and prospective study, human salivary glands were investigated after radiation treatment for head and neck cancers. The aim was to assess acinar cell loss and morphologic changes after radiation therapy and to determine whether irradiated salivary glands have regenerative potential. METHODS AND MATERIALS: Irradiated human submandibular and parotid salivary glands were collected from 16 patients at a range of time intervals after completion of radiation therapy (RT). Control samples were collected from 14 patients who had not received radiation treatments. Tissue sections were analyzed using immunohistochemistry to stain for molecular markers. RESULTS: Human submandibular and parotid glands isolated less than 1 year after RT showed a near complete loss of acinar cells. However, acinar units expressing functional secretory markers were observed in all samples isolated at later intervals after RT. Significantly lower acinar cell numbers and increased fibrosis were found in glands treated with combined radiation and chemotherapy, in comparison to glands treated with RT alone. Irradiated samples showed increased staining for duct cell keratin markers, as well as many cells coexpressing acinar- and duct cell-specific markers, in comparison to nonirradiated control samples. CONCLUSIONS: After RT, acinar cell clusters are maintained in human submandibular glands for years. The surviving acinar cells retain proliferative potential, although significant regeneration does not occur. Persistent DNA damage, increased fibrosis, and altered cell identity suggest mechanisms that may impair regeneration.

Malignant peripheral nerve sheath tumors (MPNST): a SEER analysis of incidence across the age spectrum and therapeutic interventions in the pediatric population.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are very rare in the general population and challenging to treat. A paucity of data exists regarding the incidence of MPNST across all age groups and treatment outcomes in the pediatric population. We aimed to characterize both using the Survival, Epidemiology, and End Results (SEER) database. PROCEDURE: The SEER-18 database with information on the United States population from 1973 to 2009 was queried for cases of MPNST. For incidence data, 1,182 cases were found among the general population. Of those, 165 cases were in individuals aged 0-19. After exclusions, 139 cases from the SEER-18 database met study criteria for outcomes analysis. For each patient, variables including gender, age, race, stage (localized, regional, or distant), surgical treatment, and radiotherapy were obtained. RESULTS: The overall incidence of MPNST was 1.46 per million person-years, with increased incidence among the elderly. In the pediatric population, the incidence was 0.56 per million person-years, and was higher among post-pubertal children aged 10-19. Median overall survival in the pediatric population was 30 months, with only localized disease and treatment with surgery being positive prognostic factors on multivariate analysis. CONCLUSIONS: MPNST is a rare disease and, among children, is most frequent seen in adolescents. Surgery is crucial as first-line treatment for MPNST, especially if the tumor is localized at diagnosis. In patients with non-localized MPNST, the disease remains extremely difficult to manage, and both surgery and radiotherapy are interventions that should be considered.

Preliminary results of ex vivo multispectral photoacoustic imaging in the management of thyroid cancer.

OBJECTIVE: The purpose of this study was to validate whether ex vivo multispectral photoacoustic imaging can be used to differentiate malignant tissue, benign nodules, and normal human thyroid tissue. SUBJECTS AND METHODS: Fifty patients undergoing thyroidectomy because of thyroid lesions participated in this study. Multispectral photoacoustic imaging was performed on surgically excised thyroid tissue, and chromophore images that represented optical absorption of deoxyhemoglobin, oxyhemoglobin, lipid, and water were reconstructed. After the imaging procedure, the pathologist marked malignant tissue, benign nodules, and normal regions on histopathologic slides, and digital images of the marked histopathologic slides were obtained. The histopathologic images were coregistered with chromophore images. Areas corresponding to malignant tissue, benign nodules, and normal tissue were defined on the chromophore images. Pixel values within each area were averaged to determine the mean intensities of deoxyhemoglobin, oxyhemoglobin, lipid, and water. RESULTS: There was a statistically significant difference between malignant and benign nodules with respect to mean intensity of deoxyhemoglobin (p = 0.014). There was a difference between malignant and normal tissue in mean intensity of deoxyhemoglobin (p = 0.003), lipid (p = 0.001), and water (p < 0.0001). A difference between benign nodules and normal tissue was found in mean intensity of oxyhemoglobin (p < 0.0001), lipid (p < 0.0001), and water (p < 0.0001). The sensitivity, specificity, and positive and negative predictive values of the system tested in differentiating malignant from nonmalignant thyroid tissue were 69.2%, 96.9%, 81.8%, and 93.9%. CONCLUSION: The preliminary results of this ex vivo human thyroid study suggest that multispectral photoacoustic imaging can be used to differentiate malignant and benign nodules and normal human thyroid tissue.

Breast metastases to thyroid gland.

Metastases to the thyroid gland are uncommon. We present the sonographic features of metastatic breast adenocarcinoma to the thyroid in a 67-year-old woman. The lesion measured up to 0.9 cm in diameter, contained an echogenic focus with associated ring-down, and was predominantly cystic, thereby resembling a benign nodule. Because of the patient's history of breast adenocarcinoma, the nodule nevertheless underwent fine-needle aspiration. The unusual appearance of the thyroid nodule underscores the importance of considering patient history in deciding whether obtaining tissue diagnosis of thyroid nodules is warranted.

Pearls and pitfalls of thyroid nodule sonography and fine-needle aspiration.

PURPOSE: To review the ultrasound appearances of thyroid nodules with an emphasis on morphological features and to illustrate pearls and pitfalls related to ultrasound interpretation and fine-needle aspiration. METHODS: The ultrasound features of 156 consecutive thyroid nodules with available cytological diagnoses were retrospectively reviewed. The presence of "honeycomb" morphology, aspect ratio, taller-than-wide shape, presence of colloid, consistency, echogenicity, presence of halo, margin definition, multiplicity of the nodules, largest nodule dimension, and lesion vascularity were compared between benign and malignant nodules. RESULTS: Sonographic features that are significantly more common among malignant lesions include the presence of microcalcifications, coarse internal calcifications, markedly hypoechoic components, mostly solid-to-solid contents, infiltrative or microlobulated margins, taller-than-wide shape, and a high aspect ratio (0.85 vs 0.71). Characteristics that are statistically significantly associated with benignity include peripheral calcification and purely cystic composition. The honeycomb morphology was 100% specific for nodular hyperplasia. Benign and malignant follicular and Hürthle cell neoplasms can have identical sonographic and cytological features. Colloid on both ultrasound and cytology may be found in malignant lesions, whereas microcalcifications can sometimes be found in benign lesions. Cystic components in malignant nodules are not uncommon and should not be dismissed as benign on this basis alone. Fine-needle aspiration may alter the appearance of thyroid nodules. CONCLUSIONS: Certain morphological sonographic features are helpful for differentiating between benign and malignant thyroid nodules and guided subsequent management. However, thyroid nodule ultrasound and fine-needle aspiration must be interpreted with awareness of potential pitfalls.

High-risk HPV testing in women 30 years or older with negative Papanicolaou tests: initial clinical experience with 18-month follow-up.

Cervical screening with combined cytology and high-risk human papillomavirus (HR-HPV) detection has been approved for women 30 years or older. We investigated the clinical use of cotesting for women with negative Papanicolaou tests. Follow-up cytology, HR-HPV test, and biopsy findings were identified during an 18-month period. In 1 year, 2,719 cotests from 2,686 women were identified; 146 were positive for HR-HPV. Among women with positive HR-HPV testing, 120 had follow-up, including 70 with repeated cotesting, and 3 had high-grade dysplasia identified (2.5% of women with follow-up). In 1,334 women with initial double-negative cotest results who had repeated cytologic testing within 18 months, 2 high-grade dysplasias were found (0.1%). The vast majority of cotest results are double-negative. Among tests that show HR-HPV positivity, the prevalence of underlying high-grade dysplasia is low. About half of all women who undergo cotesting receive follow-up that is not in accord with published guidelines.

Routine review of ascites fluid from patients with cirrhosis or hepatocellular carcinoma is a low-yield procedure: an observational study.

BACKGROUND: Patients with cirrhosis develop ascites for physiologic reasons that are unrelated to malignant progression. However, physicians performing paracentesis in these patients, often send fluid to the cytology laboratory, sometimes specifically looking for hepatocellular carcinoma (HCC). We have investigated the diagnostic yield of these specimens. MATERIALS AND METHODS: A computerized pathology database search for all ascites fluid cases submitted to the cytology laboratory at a major liver transplant center between November 2004 and April 2008 was performed. Clinical history was obtained for each case. Patients with cirrhosis, with or without HCC, were included in the study. Cytologic diagnoses were compiled and follow-up information was obtained for cases with non-negative findings. RESULTS: A total of 167 specimens from 133 patients ranging from 29 to 85 years of age (mean 56 years) were submitted over the said time period. The causes of cirrhosis included: alcohol - 44; Hepatitis C - 30; Hepatitis B - 6; non-alcoholic steatohepatitis - 7; cryptogenic - 18; other single causes - 6; and multifactorial (alcohol and hepatitis viruses) - 22. Hepatocellular carcinoma (HCC) was present or strongly suspected in 17 patients and had been previously resected in two others. The status of fifteen patients was post liver transplant, with recurrent liver failure. Human immunodeficiency virus was present in seven patients and eight patients had a history of non hepatic malignancies. Among the specimens, 162 were negative, two had atypical lymphocytes worked up for lymphoma, and three had atypical epithelioid cells; none was positive for HCC. Immunohistochemistry demonstrated a mesothelial origin for the atypical epithelioid cells in two cases; in the third case, the patient died shortly after the specimen was collected, with no radiological evidence of HCC. CONCLUSION: Ascites fluid cytology specimens in patients with cirrhosis, even those known or suspected to have HCC, are almost always negative. Atypical cells seen in such specimens should be treated with skepticism since the likelihood that they represent peritoneal spread of HCC is low..

Fine-needle aspiration of dedifferentiated acinic cell carcinoma: Report of a case with cyto-histological correlation.

Dedifferentiated Acinic Cell Carcinoma (DAcCC) is a rare salivary gland malignancy. It has a high tendency to recur and metastasize and thus has a poor prognosis. So far, to our knowledge, only one case of DAcCC has been reported in the cytology literature. Herein, we describe a second case of DAcCC from a fine-needle aspiration (FNA) along with its subsequent histological correlation.

Should women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, receive reflex human papillomavirus-DNA testing?

BACKGROUND: The 2001 American Society for Colposcopy and Cervical Pathology Consensus Guidelines recommend that women who have Papanicolaou (Pap) smears diagnosed as atypical squamous cells (ASC), cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) should be referred for immediate colposcopic examination. The objective of this pilot study was to evaluate whether reflex human papillomavirus (HPV)-DNA testing performed on smears diagnosed as ASC-H may obviate the need for immediate colposcopic examination. METHODS: All ThinPrep Pap smears that were diagnosed as ASC-H or atypical squamous metaplastic cells (ASMT) between 2001-2003 and that had HPV-DNA testing and subsequent histologic and/or cytologic follow-up were evaluated. Those smears that were diagnosed as ASMT were reviewed and reclassified under the 2001 Bethesda System as either ASC of undetermined significance (ASCUS) or ASC-H. Smears that were diagnosed as ASCUS were excluded from the study. RESULTS: The study included of 48 smears that were diagnosed as ASC-H. All patients with biopsy-proven HSIL had positive high-risk (HR)-HPV results (100% negative predictive value). Approximately 80% of patients with ASC-H who had biopsy-proven, low-grade intraepithelial lesion on follow-up had positive HR-HPV results. Among the patients who had ASC-H with negative follow-up, 50% had positive HR-HPV results, and 50% had negative HR-HPV results. CONCLUSIONS: Among patients with ASC-H, a negative HR-HPV result was found to be an excellent predictor of the absence of HSIL. The results of this pilot study suggested that HPV-DNA testing may serve as a means to better select which patients with ASC-H on Pap smear should undergo colposcopic examination. This approach potentially may reduce medical costs and eliminate the need for routine colposcopic examination among patients with ASC-H Pap smears.

Mucinous adenocarcinoma of ectopic breast tissue of the vulva.

Ectopic breast tissue has been described rarely in the vulva and is known to develop a variety of pathologic changes. Our review of the literature found a total of 11 reported cases of primary infiltrating ductal adenocarcinoma arising in ectopic breast tissue of the vulva. We report what we believe is the first case of primary mucinous adenocarcinoma arising in ectopic breast tissue of the vulva diagnosed by characteristic histopathologic features and immunohistochemical stain results. We discuss the criteria used in diagnosis of primary breast carcinoma of the vulva and review previously reported cases.