Pediatric Hypersensitivity Pneumonitis: Clinicopathologic Characteristics of Two Cases with Fungal Triggers.

Background Hypersensitivity pneumonitis (HP) infrequently presents in childhood. Asthma or a pneumonia-like clinical presentation may lead to diagnostic delay, especially in children. Case Report: We present two cases of HP, a 6-year-old (Case 1) male and a 5-year-old (Case 2) female. Both cases had a negative infectious work-up and patchy ground glass lung opacities on chest computed tomography. Lung biopsies demonstrated lymphocytic bronchiolitis with granulomatous interstitial and peribronchial inflammation. Serology demonstrated elevated immunoglobulin precipitins toward Thermoactinomyces and Aspergillus species in Case 1 and Aspergillus fumigatus in Case 2. Both patients received steroid therapy and had symptom resolution. Conclusions: A diagnosis of HP should be considered in pediatric lung biopsies with granulomatous interstitial and peribronchial inflammation, if infectious etiologies are excluded. Integration of clinical, radiological, and laboratory findings can facilitate a timely diagnosis.

p16INK4a as a proliferation marker unrelated to HPV expression in odontogenic cysts and tumors.

INTRODUCTION: p16INK4a 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. METHODS: With 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. RESULTS: Results 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. CONCLUSION: This 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.

Understanding and Overcoming the Pitfalls in Cytopathological Diagnosis of Hyalinizing Trabecular Tumor of Thyroid.

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.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.

Validation and implementation of telecytology at an academic medical center using digital cameras and Microsoft Teams software.

INTRODUCTION: Rapid On-Site Evaluation of cytological samples obtained through fine needle aspiration for adequacy is a critical component of a cytology service; however, it imposes a significant time and cost burden for the practicing pathologist and the cytology service. Telecytology enables adequacy assessment by a pathologist remotely, greatly saving time. Telecytology also allows slide preparation and manipulation at the procedure site by an employee with less training requirements, liberating the cytotechnologist to screen cases and perform other laboratory duties - an important aspect to consider during times of cytotechnologist shortages. We propose a telecytology system with a simple setup of a microscope, microscope camera, laptop, and Microsoft Teams software. MATERIALS AND METHODS: We designed a system consisting of a mobile cart, backup battery, microscope, digital camera, and a laptop computer with microscope imaging software and Microsoft Teams software for image transmission. Validation was performed by 4 pathologists making adequacy assessments on randomly selected previously signed out cases using the telecytology system. RESULTS: Our validation of this system demonstrated a greater than 90% concurrence rate between the original adequacy call and the call made by pathologists using the telecytology system - a benchmark used by most, if not all, published validations of similar telecytology systems. In addition, the adequacy assessment concordance rate between select pathologists exceeded 90%. CONCLUSIONS: In summary, our telecytology system provides excellent adequacy services for the clinicians and patients we serve. The Microsoft Teams software is a great tool for transmission of video microscopy. This system will be used with the goal of saving time and increasing efficiency for the cytopathology department.

Metastatic High-Grade Endometrial Stromal Sarcoma with BCOR Translocation to the Pleural Fluid: A Case Report.

Sarcomas in cytology fluids are uncommon, accounting for an estimated 3-6% of malignant effusions. High-grade endometrial stromal sarcomas are uncommon malignancies, whose true frequency is not well defined. We present a case of high-grade endometrial stromal sarcoma with a BCOR translocation metastatic to the pleural fluid. A 31-year-old female with a long-standing history of abnormal uterine bleeding underwent needle core biopsy, which showed a high-grade endometrial stromal sarcoma with a BCOR translocation. In the months following her diagnosis, the patient underwent multiple cycles of chemotherapy along with radiation therapy, but had disease progression. She then presented with bilateral pleural effusions. Cytology from the pleural effusions showed single cells and three-dimensional clusters of spindle-shaped to epithelioid cells. The cell block showed many groups of the atypical cells. The histologic and immunophenotypic features were consistent with metastatic endometrial stromal sarcoma. Ten months after initial diagnosis and two months after positive pleural fluid cytology the patient was deceased. Malignant pleural fluids with sarcoma metastases are not common. Endometrial stromal sarcomas are infrequent malignancies and those with BCOR translocations are recently described with a small number of cases reported. Pleural fluid metastasis of high-grade endometrial stromal sarcoma with BCOR translocation has not, to our knowledge, been described in the literature.

Diagnostic difficulties in non-tuberculous mycobacterial infection in lung transplant recipients.

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life-threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid-Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR-restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.

Educational Case: Group B Streptococcus Meningitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Hands in medicine: understanding the impact of competency-based education on the formation of medical students' identities in the United States.

PURPOSE: There have been critiques that competency training, which defines the roles of a physician by simple, discrete tasks or measurable competencies, can cause students to compartmentalize and focus mainly on being assessed without understanding how the interconnected competencies help shape their role as future physicians. Losing the meaning and interaction of competencies can result in a focus on 'doing the work of a physician' rather than identity formation and 'being a physician.' This study aims to understand how competency-based education impacts the development of a medical student's identity. METHODS: Three ceramic models representing three core competencies 'medical knowledge,' 'patient care,' and 'professionalism' were used as sensitizing objects, while medical students reflected on the impact of competency-based education on identity formation. Qualitative analysis was used to identify common themes. RESULTS: Students across all four years of medical school related to the 'professionalism' competency domain (50%). They reflected that 'being an empathetic physician' was the most important competency. Overall, students agreed that competency-based education played a significant role in the formation of their identity. Some students reflected on having difficulty in visualizing the interconnectedness between competencies, while others did not. Students reported that the assessment structure deemphasized 'professionalism' as a competency. CONCLUSION: Students perceive 'professionalism' as a competency that impacts their identity formation in the social role of 'being a doctor,' albeit a competency they are less likely to be assessed on. High-stakes exams, including the United States Medical Licensing Exam clinical skills exam, promote this perception.