Colonic oxygen microbubbles augment systemic oxygenation and CO2 removal in a porcine smoke inhalation model of severe hypoxia.

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n = 6 colonic OMB, n = 6 no treatment) ranging from 39 to 51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest X-ray. Colonic OMB infusion (75-100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2 ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9 ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic delivery of OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.

Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Urine Cytology Findings in Cases of Pseudocarcinomatous Urothelial Hyperplasia of the Bladder Often Represent a Diagnostic Challenge.

CONTEXT.­: Pseudocarcinomatous urothelial hyperplasia (PCUH) architecturally and cytologically mimics cancer. The urine cytology features of PCUH have not been described. OBJECTIVE.­: To describe PCUH features in urine cytology. DESIGN.­: We reviewed urine cytology cases with concurrent PCUH tissue specimens from 5 academic institutions and classified them by using The Paris System criteria. RESULTS.­: Thirty-nine patients included 31 men and 8 women with a mean age of 67 years (range, 39-87 years). All patients had prior pelvic irradiation, and most presented with hematuria (n = 27). The specimens included voided urine (n = 16); bladder washing (n = 11); and urine, not otherwise specified (n = 12). The specimen preparation included cytospin (n = 29) and ThinPrep (n = 10). Original interpretations were negative for high-grade urothelial carcinoma (n = 28), atypical urothelial cells (AUCs; n = 10), and high-grade urothelial carcinoma (HGUC; n = 1). Twenty-five urine specimens (64%) had findings of PCUH. These specimens were moderately cellular and composed of sheets, cohesive groups, or isolated urothelial cells. Nucleoli were present in 23 cases. The nuclear membrane was smooth to irregular (n = 9), smooth (n = 8), and irregular (n = 8). The chromatin was glassy (n = 8), vesicular (n = 7), hyperchromatic (n = 7), and vesicular to finely granular (n = 3). The cytoplasm varied from dense squamoid, to finely vacuolated, to vacuolated. Nucleomegaly was observed in all 25 specimens, and nuclear-cytoplasmic ratio greater than 0.5 was seen in 11 of 25 cases (44%). The background contained acute inflammation (n = 14), was clean (n = 9), and contained red blood cells (n = 2). All cases originally interpreted as AUCs and HGUC had PCUH features. CONCLUSIONS.­: PCUH urine features can overlap with AUCs, HGUC, and other nonurothelial malignancies. In our cohort, 44% (11 of 25) of urine specimens with PCUH changes were initially misclassified. Recognition of cytologic features of PCUH is important to avoid overcalling reactive changes.

Curvularia and the Brain: Case Demonstration of Optimal Management.

Background: Curvularia is a ubiquitous fungus found in tropical climates and has been reported to grow on marijuana leaves. Rarely, it can infect humans and propagate from the nasal sinuses into the brain. Case: A 28-year-old immunocompetent patient presented with history of nasal polyps, headache, and subtle visual deficits on the right. Imaging revealed what appeared to be an invasive mass growing through the ethmoid and sphenoid sinuses into the anterior cranial fossa. Results: Otolaryngology performed an endoscopic nasal biopsy with pathology and cultures consistent for Curvularia (figure 6). A combination case with neurosurgery and otolaryngology was planned. Surgeons used a bifrontal craniotomy and endonasal approach for gross total resection. Following resection, the patient was placed on 4 weeks of amphotericin treatment followed by 12 months of voriconazole based on recommendations by infectious disease. The patient has been stable since surgery. Conclusion: Curvularia is a rare but potentially life threatening central nervous system infection that can be acquired from inhalational marijuana use. This illustrative case shows the importance of aggressive debridement followed by broad spectrum antifungal treatment to optimize outcome. With marijuana's increasing popularity, Curvalaria should be included on the differential diagnosis.

Recurrent Cushing Syndrome From Metastatic Adrenocortical Carcinoma With Fumarate Hydratase Allelic Variant.

Background: Adrenal Cushing syndrome (CS) is usually benign in etiology; however, although rarely, it can be due to adrenocortical carcinoma (ACC); in which case, diagnosis and management are quite complicated. Case Report: A 34-year-old woman presented with worsening confusion, weight gain, new-onset diabetes, and hypertension. Her history was significant for a 7.4-cm left adrenal mass and CS, which were treated with left adrenalectomy 2 years ago. She received hydrocortisone replacement therapy after the surgery, which was discontinued on admission when evaluation showed hypokalemia, hypercortisolemia, and undetectable adrenocorticotropic hormone. Subsequent testing included 1-mg and 8-mg dexamethasone suppression tests, which did not suppress cortisol; late-night salivary cortisol measurement, which yielded a very high salivary cortisol level; and 24-hour urinary cortisol measurement. The level of 11-deoxycortisol was elevated. A computed tomography scan revealed multiple hepatic lesions, which were fluorodeoxyglucose avid, and a biopsy confirmed metastatic ACC. She received treatment with mitotane, metyrapone (later changed to mifepristone), doxorubicin, cisplatin, and etoposide. Over 8 weeks, mitotane levels became therapeutic at 20 mcg/mL, the hepatic masses decreased in size, and she transitioned to adrenal insufficiency and improved glycemic control. Next-generation sequencing of liver biopsy and germline testing revealed a frameshift loss-of-function allelic variant in the FH gene that encodes the protein fumarate hydratase. Discussion: We report a case of recurrent CS due to metastatic ACC in a patient with a previously resected adrenal adenoma and FH allelic variant. Conclusion: Metastatic ACC presenting with severe CS presents a diagnostic and management challenge where combination therapy guided by a multidisciplinary team is essential. FH allelic variant may contribute to ACC progression.

Metastatic Clear Cell Renal Cell Carcinoma Involving the Thyroid Gland: A Clinicopathologic Study of 17 Patients.

Background. Metastatic clear cell renal cell carcinoma (RCC) is one of the most common secondary thyroid malignancies. Diagnosis can be challenging, particularly if presenting many years after initial diagnosis. We reviewed clinicopathologic features and immunoprofile of metastatic clear cell RCC in thyroid. Design. We identified 17 patients from 2003-2021. Clinical data were obtained from medical records, and slides were retrieved and reviewed. Results. Seventeen patients (12 male and 5 female) included 12 thyroidectomies, 3 core biopsies, 1 excisional biopsy, and 1 fine-needle aspiration. The average patient age was 68.7 years (range, 45-88 years). Sixteen patients had history of clear cell RCC, and in 1 patient, the clear cell RCC was discovered after the thyroid metastasis was found. Thyroid gland metastases were on average diagnosed 90.7 months after the diagnosis of the renal primary (range, 24-240 months). Patients presented with a new palpable mass (n = 11) or dyspnea/stridor (n = 1). Five tumors were incidentally found via surveillance imaging. In 2 patients, metastases occurred within follicular thyroid neoplasms. All metastases showed conspicuous sinusoidal vasculature between the tumor nests and areas of myxoid degeneration. A prominent thick fibromuscular pseudocapsule was evident in 10 resections. Immunohistochemistry (n = 5) showed that the metastases were positive for PAX8, CA9, and CD10, while negative for keratin 7, thyroglobulin, and TTF1. Conclusions. Metastatic clear cell RCC involving the thyroid gland is infrequent and typically occurs remotely after the initial diagnosis. Cytologic and histologic features may show significant overlap with primary thyroid lesions. Immunohistochemistry can help reliably distinguish metastases from primary thyroid neoplasms.

Leiomyosarcoma of the Nasal Cavity and Paranasal Sinuses: A Case Report and Comprehensive Review of the Literature.

Sinonasal leiomyosarcoma (LMS) is a rare and aggressive mesenchymal tumor with smooth muscle differentiation. The sinonasal tract is an unusual primary site for LMS, as scant smooth muscle exists in this location, with only 75 cases reported in the English literature including the case presented herein. Sinonasal LMS is considered an aggressive head and neck tumor with significant potential for recurrence and metastasis. Since recurrence is high and the potential for late metastasis exists, lifelong follow-up in these patients would be beneficial, especially among those with previous history of RB.

Metastatic mucoepidermoid carcinoma to the pleura: a case report.

BACKGROUND: Mucoepidermoid carcinoma is the most common malignant neoplasm arising from the salivary glands (Ali et al. in J Ayub Med Coll Abbottabad 20(2): 141-2, 2008, Xi et al. in World J Surg Oncol 10: 232, 2012). When arising from anatomic sites other than the salivary glands it can be a diagnostic challenge. Primary and metastatic mucoepidermoid carcinoma from and to the pleura are extremely rare entities that are frequently misdiagnosed as adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma (Xi et al. in World J Surg Oncol 10: 232, 2012). CASE PRESENTATION: We describe an unusual case of a 64-year-old Caucasian female patient with metastatic high-grade mucoepidermoid carcinoma to the pleura, morphologically resembling squamous cell carcinoma. Molecular studies of both the parotid gland and pleural tumors helped prove the metastatic nature of the pleural lesion. CONCLUSIONS:  Metastatic mucoepidermoid carcinoma to the pleura is a rare entity, frequently misdiagnosed as squamous cell carcinoma. Differentiating between a lung primary and a metastatic disease has treatment implications and prognostic significance for the patient. When morphologic and immunophenotypic overlap exists, molecular testing can help distinguish mucoepidermoid carcinoma from other neoplasms.

Mesenchymal Neoplasms of Salivary Glands: A Clinicopathologic Study of 68 Cases.

Salivary gland neoplasms are uncommon, and most exhibit epithelial differentiation. Mesenchymal neoplasms of the salivary gland are rare, and the incidence ranges from 1.9% to 5%. The aim of this study is to identify the types and clinical-pathological features of mesenchymal salivary neoplasm and review their differential diagnosis. A retrospective search for mesenchymal neoplasms of salivary glands from our institution's pathology archives from the 2004-2021 period and consultation files of one of the authors (AER) was performed. The clinical data were obtained from available medical records, and the histological slides and ancillary studies were retrieved and reviewed. We identified a total of 68 cases that form the study cohort. Thirty-five patients were male, and thirty-three patients were female, with a mean age of 48 years (range, 7 months-79 years), and the male to female ratio was 1:.94. Sixty-three (92.6%) of sixty-eight tumors were benign and included: 38 (56%) lipomas, 9 (13%) hemangiomas, 7 (10.3%) schwannomas, 3 (4.4%) neurofibromas, 3 (4.4%) lymphangioma, 2 (3%) solitary fibrous tumors, 1 (1.5%) myofibroma. Five of sixty-eight (7.4%) were malignant and included: 3 (4.4%) Adamantinoma-like Ewing sarcomas, 1 (1.5%) malignant peripheral nerve sheath tumor (MPNST), and 1 (1.5%) malignant solitary fibrous tumor. The involved sites included: parotid (55), submandibular gland (5), parapharyngeal space (5), buccal mucosa minor salivary gland (2), and sublingual gland (1). Sixty-seven patients underwent surgical resection. One patient with lymphangioma manifested a recurrence/persistence a week post-surgery. One patient with a parotid hemangioma developed post-operative numbness, and another patient developed chronic postauricular pain after surgery. Two patients with MPNST and one patient with adamantinoma-like Ewing sarcoma underwent neoadjuvant chemoradiation and were disease-free after treatment. The remaining 37 patients with available follow-up ranging from 7 days to 96 months (mean, 18 months) had a favorable outcome and were disease-free after treatment. Mesenchymal neoplasms of salivary gland are rare; most are benign and demonstrate adipocytic, endothelial, and schwannian differentiation; awareness of their development is important for adequate diagnosis. The mainstay of treatment is surgical excision, with the extent determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas and may be given in a neoadjuvant or adjuvant setting.

A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. METHODS: Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. RESULTS: Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. CONCLUSIONS: This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

Primary Sarcomas of the Larynx: A Clinicopathologic Study of 27 Cases.

Primary sarcomas of the larynx are rare and are associated with diagnostic and treatment challenges. Studies of these tumors are limited, and most examples have been reported as small series. To further increase our understanding of laryngeal sarcomas, we reviewed our experience of an adult cohort. A retrospective search for laryngeal sarcomas from our pathology archives and consultation files of one of the authors was performed. We studied 27 primary laryngeal sarcomas that included 25 males, and 2 females, with a mean age of 60 years (range 33-85). The cases included conventional chondrosarcoma (16), well-differentiated liposarcoma (2), clear cell chondrosarcoma (1), leiomyosarcoma (2), high grade myxofibrosarcoma (2), high grade myofibroblastic sarcoma (1), low-grade myofibroblastic sarcoma (1), malignant granular cell tumor (1), and Kaposi sarcoma (1). Data on treatment and follow-up was available in 17 and 16 cases, respectively. 12 patients underwent partial laryngeal resection; five had total laryngectomy, and the patient with Kaposi sarcoma received combined highly active antiretroviral therapy and chemotherapy. Three patients developed local recurrence, and two patients developed metastases. The remaining patients with follow up had a favorable outcome and were disease-free after treatment. The important differential diagnosis of spindle cell sarcoma is sarcomatoid squamous cell carcinoma, and their distinction often requires extensive sampling of the mucosal surface and immunohistochemical analysis. The mainstay of treatment for laryngeal sarcomas is surgical removal, with the extent dictated by tumor type and grade. Adjuvant therapy is reserved for high-grade sarcomas and may be given in a neoadjuvant or adjuvant setting.

Cardiac Myxoma: Review and Update of Contemporary Immunohistochemical Markers and Molecular Pathology.

Cardiac myxoma is an uncommon benign mesenchymal neoplasm of the heart. It usually arises in the left atrium, near the valve of the fossa ovalis, and most frequently affects adults in the third through the sixth decades of life. It is hypothesized to arise from subendothelial vasoformative reserve cells or primitive cells that differentiate along the lines of the endothelium, but this remains speculative. Microscopically, the neoplastic cells are arranged individually, and nests, and are oriented in single or multiple layers around vascular channels. The neoplastic cells are immunoreactive for vimentin, calretinin, S100, nonspecific enolase, factor VIII, CD31, and CD34. The tumor can have diverse clinical presentations depending on its location and extent of disease and is predisposed to embolization. The current treatment is prompt surgical excision.

Medullary Thyroid Carcinoma Presenting as Metastatic Disease to the Breast.

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that is derived from C cells of the thyroid gland. It is a rare aggressive tumor, known to metastasize to lymph nodes, liver, bones, and lungs. A 41-year-old female, who presented with a breast mass, was initially diagnosed with invasive ductal carcinoma. She was also found to have a thyroid mass which was later diagnosed as MTC. On a rereview of the breast pathology, the morphologic features were strikingly similar to the MTC. Further investigation revealed that this was in fact a very rare case of MTC that had metastasized to the breast. We have identified 20 cases of MTC metastasizing to the breast in the literature that supports its occurrence as a real possibility. Albeit rare, medullary thyroid carcinoma should be considered in the differential diagnosis of a breast mass.

P16 and human papillomavirus in sinonasal squamous cell carcinoma.

Human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SCC) is a well-known cause and prognostic indicator, and the utility of p16 as a surrogate marker for HPV status has been established. P16 and its relationship with HPV have not been defined in sinonasal malignancy nor has a link with outcomes been established. Patients with sinonasal SCC from 2011 to 2017 were identified from our pathology database. P16 immunohistochemistry and HPV RNA in situ hybridization were performed on tissue specimens. Forty-seven patients were included. Disease-free survival for p16+ patients was significantly higher than p16- patients (P = .043). Fewer HPV+ patients died (P = .052) or experienced recurrence (P = .0437). Odds ratio between p16 and HPV status was 14.19 (95% CI: 1.72, 442.03). Our findings demonstrate improved survival in both the p16+ and HPV+ groups and a positive association between p16 and HPV. There may be similar potential for modifying classification for HPV+ sinonasal SCC.

A Rare Case of Plasma Cell Granuloma.

Plasma cell granulomas (PCGs) or inflammatory pseudotumors are nonneoplastic lesions that consist of predominantly antibody-secreting plasma cells and innate immune cells such as neutrophils, macrophages, and eosinophils. Unlike in multiple myeloma, the plasma cells are polyclonal and present in a spindly fibroblast-rich stromal background. These lesions mainly occur in the lungs; however, they can arise in other organs. PCGs from the gingiva are extremely rare, and a proper diagnosis is crucial to treat these patients further. These tumors have an increased number of plasma cells that are immunoreactive with CD138 and are polyclonal for kappa and lambda light chains, confirming these proliferations' nonneoplastic nature. Surgical resection with clear margins, when possible, is the primary choice of treatment. Radiation and anti-inflammatory steroid therapy are other therapeutic approaches. Critical and careful examination by a pathologist is necessary to rule out plasma cell neoplasms. Here, we report a rare occurrence of gingival PCG in an elderly male.

An Unusual Hybrid Salivary Gland Tumor: Molecular Analysis Informs the Potential Pathogenesis of This Rare Neoplasm.

BACKGROUND: The presence of two or more tumor entities growing in adjacent locations within the salivary gland is very rare, and pathologic studies on such lesions are limited, particularly those with molecular information. Since the clinical history and imaging studies are usually nonspecific, accurate diagnosis and clinical management largely depend on a thorough histological examination. METHODS AND RESULTS: We describe a 71-year-old man with an unusual case of hybrid salivary gland tumor composed of mucoepidermoid carcinoma and basal cell adenoma. Molecular analysis revealed differing driver genetic alterations in each component. CONCLUSIONS: Hybrid salivary gland tumors are rare, and their pathogenesis is controversial. The combination of mucoepidermoid carcinoma and basal cell adenoma has not been previously described. While malignant transformation of adenoma to carcinoma seems plausible, gene sequencing was more suggestive of their independent derivation. Key to appropriate surgical management is identifying the more aggressive component, ideally at the time of intraoperative consultation.