Cytologic features of metastatic epithelioid uterine leiomyosarcoma to the pancreas.

Although uterine leiomyosarcoma (ULMS) is a rare disease, it accounts for a significant proportion uterine cancer-related deaths due to frequent metastasis and chemoresistance. The WHO currently recognizes the conventional (spindle), myxoid, and epithelioid variants of ULMS, the latter of which is the rarest, least understood, and cited as clinically more aggressive than the other variants. Descriptions of the histologic features of epithelioid ULMS are extremely limited, and are absent from the cytology literature which has only published descriptions of conventional ULMS or epithelioid variants of other LMS primaries. Therefore, we present a unique case of metastatic epithelioid ULMS to an unusual location, the pancreas, along with its cytologic features on endoscopic ultrasound-guided fine needle aspiration not previously described including pseudoglandular arrangements, scant cytoplasm, and frequent molding.

Pathology Trainees Gain Clinical Pathology Experience as Lab Consultants Through Auditing Myeloid Mutation Panel Send-Out Tests: Hitting Two Birds With One Stone?

CONTEXT.­: Inappropriate laboratory testing and the threat it poses to patient care and rising health care costs has become an important focus in the medical literature. Pathology residents, as physicians with an intimate knowledge of laboratory testing, may be uniquely equipped with the tools to intervene in situations of inappropriate testing and also benefit from lab use experience as part of their clinical pathology training. OBJECTIVE.­: To employ a resident-driven initiative aimed at incorporating pathology residents as consultants for appropriate ordering of high-volume, send-out myeloid mutation panel testing. DESIGN.­: During a 6-month study period, all myeloid mutation panel send-out tests were screened by senior pathology residents on their clinical chemistry rotation prior to approval at an academic medical center. A retrospective review of myeloid mutation panels from the prior 6 months was conducted with the same criteria to determine effectiveness of the intervention. RESULTS.­: Of the 234 tests ordered during the study period, screening resulted in cancellation of 17% (n = 39), with proportional cost savings. The number of inappropriate orders successfully cancelled was significant compared with the preintervention period (control, 0%; intervention, 76.5%; P < .001, Fisher exact test). There was no significant difference in the proportion of inappropriate tests before and after intervention. CONCLUSIONS.­: Although test ordering patterns did not substantially change during the intervention period, pathology residents effectively reduced inappropriate myeloid mutation panel testing through prospective send-out auditing, leading to significant cost savings. Moreover, assessment of test use and appropriateness provided critical clinical pathology training within the areas of hematology, molecular genetics, and laboratory management.

Sarcomatoid Mesothelioma with Bland Histologic Features: A Potential Pitfall in Diagnosis.

Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little if any collagen; no chest wall, soft tissue, or fat; and mesothelial markers were negative. The cells were positive for pancytokeratin and GATA3 by immunohistochemistry, and in situ hybridization showed a "negative" result for homozygous loss of CDKN2A; however, there was partial (heterozygous) loss of one allele. A diagnosis of atypical spindle cell proliferation was made based on these findings. Several months later, the patient had a repeat pleural biopsy that showed spindled cells with more pleomorphism, areas of invasion into the chest wall, and the same partial loss of CDKN2A, consistent with a sarcomatoid mesothelioma. This case underscores the challenges present on small biopsy specimens, the fact that sarcomatoid mesotheliomas can be relatively bland appearing with focal pleomorphism, and that heterozygous loss of CDKN2A should be considered a positive result indicative of a neoplastic process.

Epithelioid hemangioma involving large arteries in the skin.

Epithelioid hemangioma (EH) is a benign vascular lesion, typically consisting of small vascular channels lined by epithelioid endothelial cells and associated with a dense lymphocytic infiltrate with eosinophils. Here, we report a rare case of EH involving large arteries. The patient presented with a 9-month history of an asymptomatic nodule on the forehead, which was thought to be an epidermal inclusion cyst. Skin biopsy revealed large arteries with clusters of epithelioid cells in the vascular walls and lumen. Scattered eosinophils were noted in the walls. Adjacent areas showed groups of small-caliber vessels lined by prominent endothelial cells and associated with a dense lymphoid infiltrate with eosinophils. No significant cytologic atypia was noted. Given the presence of the classic small-vessel involvement, along with CD31 reactivity for the epithelioid cells in the large vessels, the findings are classified as EH involving large arteries, which is an uncommon subtype. There have only been a handful of such cases reported in the literature.

Metastatic mesonephric-like endometrial adenocarcinoma diagnosed on transbronchial needle aspirate cytology.

Mesonephric-like adenocarcinoma is a relatively rare neoplasm with morphology similar to mesonephric adenocarcinoma but unassociated with mesonephric remnants. Its relatively recent description and rarity make it difficult to diagnose, but it has a high rate of distant metastasis, making distinction from endometrioid carcinoma important. Descriptions of its cytologic features are particularly limited. We describe a case of mesonephric-like adenocarcinoma diagnosed on transbronchial needle aspiration of the lung, that had been misdiagnosed as endometrioid endometrial adenocarcinoma on a prior hysterectomy. We discuss the characteristic cyto and histomorphology, immunoprofile, molecular alterations, and clinical significance of this uncommon tumor.

Hypercalcemia of Malignancy: Simultaneous Elevation in Parathyroid Hormone-Related Peptide and 1,25 Dihydroxyvitamin D in Sarcoma.

OBJECTIVE: Hypercalcemia is a common finding in patients who have an underlying malignancy. Only a few cases of hypercalcemia of malignancy have been linked to more than one mechanism of hypercalcemia. Here, we present a patient with liposarcoma and hypercalcemia of malignancy in the setting of simultaneous elevations in parathyroid hormone-related peptide (PTHrP) and 1,25 dihydroxyvitamin D [1,25(OH)2D] levels. Sarcoma-associated hypercalcemia is a rare disorder. METHODS: The patient was an 89-year-old woman with sarcoma-associated hypercalcemia. Multiple mechanisms were uncovered, and treatments were adjusted for them. Literature search for hypercalcemia of malignancy with multiple mechanisms was conducted. RESULTS: This is the first report describing dual mechanisms of sarcoma-associated hypercalcemia and only the fifth report on PTHrP and 1,25(OH)2D simultaneously causing hypercalcemia of malignancy. CONCLUSION: Based on this finding, we recommend measuring the 1,25(OH)2D levels in conjunction with the PTHrP level in patients with malignancy as this would allow for a more proactive approach to the diagnosis and treatment of hypercalcemia of malignancy.

Evaluation of Inappropriate COVID-19 RT-PCR Test Utilization at an Academic Medical Center.

BACKGROUND: An evolving COVID-19 testing landscape and issues with test supply allocation, especially in the current pandemic, has made it challenging for ordering providers. We audited orders of the Xpert® Xpress SARS-CoV-2 PCR with reverse transcription (RT-PCR) platform-the fastest of several other testing modalities available-to illuminate these challenges utilizing a multidisciplinary laboratory professional team consisting of a pathology resident and microbiology laboratory director. METHODS: Retrospective review of the first 5 hundred Xpert Xpress SARS-CoV-2 RT-PCR test orders from a 2-week period to determine test appropriateness based on the following indications: emergency surgery, emergent obstetric procedures, initial behavioral health admission, and later including discharge to skilled care facilities and pediatric admissions. Our hypothesis was that a significant proportion of orders for this testing platform were inappropriate. RESULTS: On review, a significant proportion of orders were incorrect, with 69.8% (n = 349, P < 0.0001) not meeting indications for rapid testing. Of all orders, 249 designated as emergency surgery were inappropriate, with 49.0% of those orders never proceeding with any surgical intervention; most of these were trauma related (64.6% were orders associated with a trauma unit). CONCLUSIONS: Significant, pervasive inappropriate ordering practices were identified at this center. A laboratory professional team can be key to identifying problems in testing and play a significant role in combating inappropriate test utilization.

Parotid Salivary Duct Carcinoma With a Prominent Squamous Component: Immunohistochemical Profile, Diagnostic Pitfalls, and Therapeutic Implications.

Salivary duct carcinoma of the parotid gland is a highly aggressive epithelial malignancy morphologically resembling high-grade, invasive, and in situ breast carcinoma. It can occasionally present with variable morphology making it diagnostically challenging in cases with unusual morphological components. Ancillary testing, particularly androgen receptor (AR) positivity on immunohistochemistry, can be very helpful in cases that demonstrate extensive squamous morphology, since AR positivity is uncommon in both the primary salivary gland and metastatic squamous cell carcinomas to the parotid. In this report, we describe a case of salivary duct carcinoma that showed only a squamous cell carcinoma component on the initial primary tumor site biopsy, as well as in subsequent contralateral neck lymph node and skin metastases. Apart from the variable morphology, the typical salivary duct and squamous cell carcinoma tumor components also showed significant immunohistochemical differences, including differential staining of human epidermal growth factor receptor 2/neu. The associated diagnostic pitfalls, distinct immunoprofiles of the tumor components, helpful adjuncts for making the correct diagnosis, and associated therapeutic implications are discussed.

A Cardiac Amyloidosis Presentation: Atrial Mass Versus Thrombus.

Cardiac neoplasms are a rare finding of which a cardiac myxoma is the most commonly encountered. Therefore, a density identified in the left atrium commonly leads to the presumptive diagnosis of an atrial myxoma. However, other pathologies, such as atrial thrombi, can mimic in clinical presentation and appearance to a myxoma. Clinically, these pathologies may lead to obstructive symptoms such as syncope, palpitations, or sudden cardiac death. At present, echocardiography, magnetic resonance imaging, or computed tomography can be used to identify such masses, but fall short of identifying the primary cause. The management of atrial thrombi is not yet fully understood and definite recommendations have not been established. We present a case of an 87-year-old man complaining of syncopal episodes found to be secondary to an incidental intracardiac density resulting from age-related amyloidosis.

Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program.

BACKGROUND: Perioperative cardiac xenograft dysfunction (PCXD) was described by McGregor and colleagues as a major barrier to the translation of heterotopic cardiac xenotransplantation into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24 to 48 hours of transplantation. We describe our experience with PCXD at a single program. METHODS: Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 monoclonal antibodies (mAb), thymoglobulin, cobra venom factor, and anti-CD40 mAb, and maintenance with anti-CD40 mAb, mycophenolate mofetil, and tapering doses of steroids. Telemetry was used to assess graft function. Extracorporeal membrane oxygenation was used to support 1 recipient. A full human clinical transplantation team was involved in these experiments and the procedure was performed by skilled transplantation surgeons. RESULTS: A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful, and all hearts were weaned from cardiopulmonary bypass without issue. Support with inotropes and vasopressors was generally required after separation from cardiopulmonary bypass. The cardiac xenografts performed well immediately, but within the first several hours they required increasing support and ultimately resulted in arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection. CONCLUSIONS: Despite excellent surgical technique, uneventful weaning from cardiopulmonary bypass, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24 to 48 hours without evidence of rejection. Modification of preservation techniques and minimizing donor organ ischemic time may be able to ameliorate PCXD.

Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs.

A combination of genetic manipulations of donor organs and target-specific immunosuppression is instrumental in achieving long-term cardiac xenograft survival. Recently, results from our preclinical pig-to-baboon heterotopic cardiac xenotransplantation model suggest that a three-pronged approach is successful in extending xenograft survival: (a) α-1,3-galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody-mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co-stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal antibody (mAb). Using this combination of manipulations, we reported significant improvement in cardiac xenograft survival. In this study, we are reporting the survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts underwent rejection at an early time point (median 70 days) despite utilization of our previously reported successful immunosuppression regimen and effective control of non-Gal antibody response. These results support our hypothesis that transgenic expression of human thrombomodulin in donor pigs confers an independent protective effect for xenograft survival in the setting of a co-stimulation blockade-based immunomodulatory regimen.