Hyalinizing trabecular tumor (HTT), a rare low-malignant-potential thyroid neoplasm, is usually treated with conservative surgery. However, cytomorphological diagnosis of HTT is challenging due to the significant overlap of nuclear features with more common malignancies such as papillary thyroid carcinoma (PTC), which usually requires more radical surgical intervention. To avoid unnecessary overtreatment, a precise diagnosis of HTT is therefore essential. Advances in molecular diagnostics provide the opportunity to overcome the limitations of cytological analysis. We present a case of HTT in a 71-year-old male who was initially suspected to be PTC based on cytopathology. However, further molecular analysis revealed PAX8::GLIS3 gene fusion, classifying the lesion as HTT and preventing surgical overtreatment. We discuss the diagnostic pitfall of cytopathology in HTT and suggest using emerging molecular genetic tools to avoid it.

Sarcoidosis is a systemic disease characterized by the formation of non-necrotizing granulomas, primarily involving the lungs and other organs such as the heart. The diagnosis of cardiac sarcoidosis can be difficult. The last set of diagnostic guidelines for diagnosis and treatment of cardiac sarcoidosis was published in 2019 by the Japanese Circulation Society (JCS). We describe a case of classic cardiac sarcoidosis and review the literature on clinical presentation, imaging, and management.

Background In patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important — those with classic histology and favorable T and M stage. Materials and methods Twenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8th edition) of T0–3, N1b with ≥ 5 positive nodes, and M0. Results The median positive node number was 10 (range, 5–31). The median adjuvant I-131 dose was 158 mCi (range, 150–219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%. Conclusion Recurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.

Sclerosing polycystic adenoma (SPA) is an uncommon entity with fewer than 100 reported cases in the literature. Predominately affecting the major salivary glands, SPA typically presents as a painless, slow-growing mass in a middle-aged woman. The lesion’s histopathologic features are reminiscent of fibrocystic changes of the breast, but recent genetic studies provide evidence for a neoplastic process. We present a case of a sclerosing polycystic adenoma in a 69-year-old female with no significant medical history who was found to have a left parotid mass. This led to a fine needle aspiration (FNA) which was non-diagnostic. Superficial parotidectomy yielded a well-circumscribed unencapsulated mass with histologic and immunohistochemical features consistent with the diagnosis of SPA. We present this case to further characterize SPA, adding to the body of literature regarding the tumor’s presentation and histopathologic and immunohistochemical features.

Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). This study describes a series of SC in minor glands with a literature review. We performed a retrospective search for oral SC, within the archives of the University of Florida, Oral Pathology and Surgical Pathology Biopsy services from 2010 to 2018. A total of 10 SCs were identified in the oral and maxillofacial region, four of which were in the minor salivary glands. The demographic, clinical, histological, and molecular findings were aggregated for all 4 cases. Patient age varied from 30 to 60 years, with an average of 45 years. Two cases each were in female and male patients. Two cases presented on the labial mucosa, and one each on the hard and soft palate. Immunohistochemical (IHC) staining showed mammaglobin positivity in all cases, GATA3 positivity in two cases, S100 positivity in three cases, and SOX10 positivity in only one case. Fluorescence in situ hybridization demonstrated positivity for ETV6-NTRK3 fusion in 4 cases. Although oral SC is rare, pathologists should be aware of the histologic overlap between the SC and other salivary gland neoplasms such as ACC and MEC. A judicious application of IHC staining would aid in diagnosis. SC should be considered in the differential diagnosis for intraoral salivary gland tumors.

Primary tumors of the heart are uncommon; even rarer are primary cardiac neuroendocrine tumors. To our knowledge, only two cases have been described to date, both being high-grade tumors. We report a solitary low-grade neuroendocrine tumor of the heart, unexpectedly discovered during aortic valve repair for infectious bacterial endocarditis on the wall of the right ventricle in a 44-year-old man with a history of balloon valvulotomy as a child. Frozen section was sent intraoperatively and demonstrated a plasmacytoid neoplasm. Final pathology of the biopsies showed a tumor composed of both cohesive and discohesive plasmacytoid cells separated by a vascular network and strands of fibrosis. The tumor showed strong reactivity for AE1/3, synaptophysin, and CDX2 with focal reactivity for chromogranin-A and CD56. Neither necrosis nor a mitotic rate of greater than 2 mitoses per 2 mm2 was seen. A colonoscopy was performed and demonstrated only a tubular adenoma. An esophagogastroduodenoscopy was unremarkable. PET-CT DOTATATE, performed after complete resection of the tumor, demonstrated no abnormal radiotracer uptake. The patient continues to do well at present, 1 year later, and reports no symptoms attributable to carcinoid syndrome or disease progression. The patient was assigned by medical oncology to yearly follow-up and imaging, and is considered to have no evidence of disease.

BACKGROUND Carcinosarcoma of the sinonasal tract is an extremely rare malignant neoplasm; it is often designated as carcinoma with spindle cell or sarcomatoid features. We report a case of carcinosarcoma arising in a pre-existing inverted Schneiderian papilloma in the left maxillary antrum and nasal cavity of a 72-year old male patient. CASE REPORT The patient had a significant history of radiotherapy for squamous cell carcinoma in the sinonasal area, 3 decades ago. The patient presented with chief complaints of left nasal blockage, nasal discharge, anosmia, and occasional epistaxis. Computed tomography scan displayed a lobular soft tissue mass resulting in narrowing of the nasopharyngeal airway with massive destruction of palatal tissue. The lesion was resected via endoscopic surgery. Macroscopically, a white fleshy appearance with necrosis was noted in the submitted specimen. Microscopically, the tumor was composed of pleomorphic epithelial and spindle cells with numerous mitoses and remarkable tissue necrosis. Residual inverted papilloma (IP) with high-grade dysplasia, and minimal foci of moderately differentiated squamous cell carcinoma (SCC) component was present at the tumor margin. A distinct zone of transition of SCC to spindle cell carcinoma (SpSCC) was noted and confirmed by focal positivity of p63 in epithelial and sacromatoid components. The pleomorphic sarcomatoid tumor was positive for vimentin with Ki67 highlighting 70% of tumor cells. A final diagnosis of sinonasal spindle cell carcinoma associated with residual inverted papilloma was rendered. CONCLUSIONS Due to the rarity of such cases, the prognosis and response to treatment is unclear. No effective directed treatment has been developed. Unfortunately, the patient refused any further treatment and died of persistent disease. To the best of our knowledge, only one case of sinonasal carcinosarcoma arising from dysplastic inverted papilloma has been reported. The distinct possibility of previous radiotherapy contributing to development of sarcomatoid features in this neoplasm should also be considered.

INTRODUCTION:Pericardial involvement of sarcoidosis is a rare cause for acute heart failure, and usually occurs as a result of the development of a pericardial effusion leading to cardiac tamponade. Even rarer still, is the manifestation of constrictive pericarditis. We report a case of sarcoidosis with lung, pleural, and pericardial involvement with effusive-constrictive pericarditis leading to cardiac tamponade.CASE PRESENTATION:A 34-year-old Caucasian man presented for evaluation of a history of worsening exertional dyspnea, edema, and weight loss. A high-resolution chest computed tomography showed diffuse pulmonary nodules with upper lobe predominance and in a perilymphatic distribution; large right pleural effusion; and large pericardial effusion with pericardial thickening. A transthoracic echocardiogram demonstrated early tamponade physiology for which a pericardial drain was placed. After removal of the drain he developed cardiogenic shock from cardiac tamponade attributed to the reaccumulation of a pericardial effusion and urgent pericardial window was performed. Serial echocardiography was concerning for organization and localization of the pericardial fluid. Cardiac magnetic resonance imaging demonstrated a significant reduction in pericardial slippage between the parietal and visceral layers around the heart collectively suggestive of constrictive pericarditis. Confirmation of effusive-constrictive pericarditis was noted on right heart catheterization. He then underwent pericardiectomy, which on histopathologic evaluation demonstrated non-necrotizing granulomas, thus confirming pericardial involvement of sarcoidosis.CONCLUSIONS:We report a case demonstrating unique manifestations of sarcoidosis; effusive-constrictive pericarditis presenting with acute congestive heart failure.

Benign metastasizing leiomyoma is a very uncommon clinicopathologic entity with unknown molecular pathogenesis. We present a case of a 40-year-old woman who has a history of surgical resection of a large uterine leiomyoma and then subsequently presented with benign metastasizing leiomyomas to her lungs. Due to her tumor being estrogen receptor (ER) positive and progesterone receptor (PR) positive, she was empirically treated with anastrozole with sustained clinical benefit. Molecular studies with Foundation One testing showed low mutational burden and mutational variants in five known cancer genes. Our findings have important clinical and pathogenetic implication for metastasizing uterine leiomyoma.

Introductionp16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse. MethodsWith IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing. ResultsResults were scored as follows: nuclear and cytoplasmic staining of <5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2), >50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result. ConclusionThis study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.

Kaposi sarcoma (KS) is a low-grade mesenchymal tumor that is often encountered in acquired immune deficiency syndrome (AIDS)-associated malignancy. The typical manifestation is primarily cutaneous involvement before disseminating to other organs in patients with advanced AIDS. In ~45% of patients with cutaneous AIDS-related KS, thoracic involvement can occur. Thoracic involvement includes lung parenchyma, pleura, and intrathoracic lymph nodes.1 Since the entry into the era of antiretroviral therapy over the last few decades, KS presenting as an endobronchial lesion has been rarely reported in the literature. We present a case of endobronchial KS with cutaneous and pulmonary involvement in a young man with advanced AIDS. CASE REPORT A 24-year-old homosexual man with past medical history of AIDS diagnosed 6 years ago, secondary syphilis, and history of biopsy-proven cutaneous KS was admitted for evaluation of altered mental status. He had been noncompliant with antiretroviral therapy, with undetectable CD4 count and a human immunodeficiency virus (HIV)-1 viral load over 623,000 copies/mL. He underwent lumbar puncture. Varicella zoster virus was detected by polymerase chain reaction method from the cerebrospinal fluid. He was treated with intravenous acyclovir. His hospital course was complicated by complaints of dry cough and dyspnea on exertion. Physical examination was notable for oral thrush, hyperpigmented lesions over the nasal ridge and lower extremities. These findings were consistent with the known diagnosis of cutaneous KS (Fig. 1). Computed tomography (CT) of the chest demonstrated bilateral spiculated nodules in a peribronchovascular pattern, and an endotracheal lesion along the left upper endotracheal mucosa (Fig. 2). Fiberoptic bronchoscopy demonstrated a polypoid lesion attached to the endotracheal mucosa occluding approximately one-third of the endotracheal lumen with surrounding confluent areas of violaceous and erythematous mucosa (Fig. A). A biopsy was obtained to characterize the endobronchial lesion. Pathologic examination demonstrated a spindle cell proliferation. Immunohistochemistry demonstrated positive nuclear staining for ETS-related gene, a transcription factor expressed in vascular tumors such as angiosarcomas, epithelioid hemangioendothelomas, and KS.2 Nuclear staining for human herpes virus 8 (HHV-8) was also positive by immunohistochemistry (Fig. 3), supporting the diagnosis of endobronchial KS. The left upper lobe bronchoalveolar lavage was Gram stain, acid fast bacilli stain, and culture negative, excluding an infectious etiology. Antiretroviral therapy was initiated. The patient tolerated the treatment well without symptoms of immune reconstitution inflammatory syndrome. He was discharged home a week after antiretroviral therapy was initiated. He was readmitted 2 weeks later with acute brain stem infarct from complete occlusion of the basilar artery requiring emergent thrombectomy complicated by reocclusion of the basilar artery and locked-in-syndrome. He was mechanically ventilated for 2 weeks. The prognosis of him having meaningful neurological recovery was very poor. His health care proxy decided to change his code status to comfort care, and the patient ultimately passed away.FIGURE 1: A biopsy-proven cutaneous Kaposi sarcoma of the lower extremity.FIGURE 2: A, The H&E demonstrated a bland spindle cells proliferation, free of mitotic figures, marked atypia and tumor necrosis. B, Immunohistochemistry of ERG demonstrated positive nuclear staining for ERG, a transcription factor that has been linked to angiogenesis. C, Immunohistochemistry for HHV-8 demonstrated positive nuclear staining for HHV-8. ERG indicates ETS-related gene; H&E, hematoxylin and eosin; HHV-8, human herpes virus 8.FIGURE 3: Computed tomography of the chest demonstrated an endotracheal lesion along the left upper endotracheal mucosa (A) and irregular nodular opacities with a peribronchovascular distribution typically represents pulmonary Kaposi sarcoma (B).FIGURE A: Fiberoptic bronchoscopy demonstrated a polypoid lesion attached to the endotracheal mucosa occluding approximately one-third of the endotracheal lumen (A) with surrounding confluent areas of violaceous and erythematous mucosa (B).DISCUSSION The most common HIV-associated malignancy is KS, although the incidence has been declining since the start of antiretroviral therapy era. It is most often seen in male individuals (male to female ratio close to 3:1). It is diagnosed with an increased rate in individuals from the Mediterranean basin, Central and Eastern Europe.3 HHV-8 infection is recognized as an essential factor in the development of KS, as KS is thought to originate from HHV-8 infected endothelial cells. This is especially true with the type A HHV-8 strain which is associated with rapid progression of KS and higher blood viral loads compare to other genotypes.4 In addition, other risk factors for KS include immunosuppression, either acquired as in the case of HIV, or iatrogenic such as in solid organ transplantation.3 Our patient had both AIDS and HHV-8 infection in the airway endothelial cells. There are 4 different types of KS characterized by the clinical setting in which they occur, including classic type usually seen in the middle-aged to elderly population, endemic type established in sub-Saharan Africans, iatrogenic type caused by immunosuppressive drugs, and AIDS-associated epidemic KS. The lesions of KS are highly vascularized and have a propensity to bleed because they are comprised of distinctive spindle cells that line blood vessels.1,5 Chest CT findings of AIDS-related KS is classically described as bilateral and symmetric ill-defined nodules in a peribronchovascular distribution, also known as flame-shaped lesions, as demonstrated in our patient's CT chest.6 The typical bronchoscopic appearance of endobronchial KS is described as erythematous, violaceous, maculopapular lesions in a discrete or confluent distribution.7 Yoo et al7 evaluated 35 patients with endobronchial KS, of which only one patient had a mass lesion appearance on bronchoscopy. Our patient had an endotracheal mass which partially occluded the trachea. We performed an endobronchial biopsy because KS presenting as an endobronchial mass is rare. Moreover, other common etiologies of endotracheal lesions, such as infection and HIV-associated malignancies, needed to be excluded. Endobronchial KS could progress to total occlusion of the tracheobronchial tree if not appropriately treated. Other diagnostic possibilities in AIDS patients with a radiologic presentation of diffuse pulmonary nodules include infections such as mycobacterial tuberculosis; opportunistic infection from pneumocystis pneumonia or cytomegalovirus pneumonia; and noninfectious etiologies such as non-Hodgkin lymphoma, adenocarcinoma, or sarcoidosis. We excluded these causes by way of a negative bronchoalveolar lavage stain, culture, and endobronchial biopsy. There is no official staging system for KS. Our literature review found that for epidemic or AIDS-related KS, a scoring system was developed by the AIDS Clinical Trials Group of the National Institute of Health. This system utilizes 3 variables that include tumor extent, immune status, and systemic symptoms.8 The staging system for classic KS is based on the disease distribution and speed of disease evolution.9 Prognosis is dependent on the type of KS. Nevertheless, our patient had disseminated disease with visceral involvement of the most aggressive form, which portends a poor prognosis. The lesions may regress in size and number with antiretroviral therapy. Literature review suggests treatment of KS with pegylated liposomal doxorubin or paclitaxel, the first and second line chemotherapeutic agents, respectively.9–11 Our patient was not a candidate for chemotherapy because of the diagnosis of a brain stem infarct complicated by lock-in syndrome and history of noncompliance to antiretroviral therapy. CONCLUSIONS This case highlights the importance of considering bronchopulmonary KS in the differential diagnoses in advanced AIDS patients presenting with a polypoid endobronchial mass. Bronchoscopy should be performed for airway inspection and to exclude other infectious or noninfectious etiologies in HIV/AIDS patients. If the diagnosis remains in question, transbronchial or endobronchial biopsy should be cautiously performed because of the increased risk of bleeding from the angiogenic effect of vascular tumors such as KS.

BACKGROUND:Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death-ligand 1 (PD-L1) expression.OBJECTIVES:Since a significant portion of lung cancer is diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA); there is a need for PD-L1 testing in these specimens. However, to date few studies have evaluated performance of cytology specimens from EBUS TBNA for PD-L1 analysis.METHODS:Patients who had a diagnosis of NSCLC and in whom ancillary testing, i.e., next generation sequencing (NGS), anaplastic lymphoma kinase (ALK), and PD-L1 expression was requested between January and May 2017 were reviewed.RESULTS:Fifty of the 112 patients reviewed had the diagnosis of NSCLC for which ancillary testing was requested. Twelve patients (24%) had squamous cell carcinoma, twenty-seven had adenocarcinoma (54%), five had NSCLC favor adenocarcinoma (10%), two had NSCLC favor squamous cell cancer (4%), and four had NSCLC not otherwise specified (NOS) (8%). Size of the lymph nodes or lesion sampled ranged from 10 to 50 mm. Four (8%) patients had insufficient number of tumor cells in the cell block for any of the ancillary molecular testing. Forty-one (82%) patients had an adequate sample for all three ancillary tests. Satisfactory results for PD-L1 expression for all cases was 86% with 14 (32%) patients having levels of PD-L1 expression >50%.CONCLUSION:EBUS TBNA is effective and has a high proportion of satisfactory results for testing PD-L1 expression on tumor cells in addition to NGS and ALK FISH.

A young boy had an enlarging right facial mass; a computed tomographic scan showed a discrete necrotic mass in the right parotid gland, and fine-needle aspirate yielded a cellular sample with spindloid features. What is your diagnosis?

Merkel cell carcinoma (MCC) is an uncommon but highly malignant neuroendocrine tumor of the skin. MCC can metastasize, but involvement of the central nervous system is rare. Here, we report a case of rapidly progressing metastatic MCC to the clivus and bilateral cavernous sinus in an immunocompromised patient. This case is unique in that it is the first case report showing MCC metastasis to the clivus from a distant site. It also demonstrates that a MCC metastasis can masquerade with symptoms of Tolosa-Hunt syndrome. A literature review on MCC with CNS metastasis is presented.

OBJECTIVES:There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era.METHODS:Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient.RESULTS:Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%.CONCLUSIONS:Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.