Pericardial Mesotheliomas.

Primary pericardial mesothelioma (PM) is a rare tumor arising from the mesothelial cells of the pericardium. It has an incidence of <0.05% and comprises <2% of all mesotheliomas; however, it is the most common primary malignancy of the pericardium. PM should be distinguished from secondary involvement by the spread of pleural mesothelioma or metastases, which are more common. Although data are controversial, the association between asbestos exposure and PM is less documented than that with other mesotheliomas. Late clinical presentation is common. Symptoms may be nonspecific but are usually related to pericardial constriction or cardiac tamponade, and diagnosis can be challenging usually requiring multiple imaging modalities. Echocardiography, computed tomography, and cardiac magnetic resonance demonstrate heterogeneously enhancing thickened pericardium, usually encasing the heart, with findings of constrictive physiology. Tissue sampling is essential for diagnosis. Histologically, similar to mesotheliomas elsewhere in the body, PM is classified as epithelioid, sarcomatoid, or biphasic, with the biphasic type being the most common. Combined with morphologic assessment, the use of immunohistochemistry and other ancillary studies is helpful for distinguishing mesotheliomas from benign proliferative processes and other neoplastic processes. The prognosis of PM is poor with about 22% 1-year survival. Unfortunately, the rarity of PM poses limitations for comprehensive and prospective studies to gain further insight into the pathobiology, diagnosis, and treatment of PM.

Prognostic implications of and clinical risk factors for acute lung injury and organizing pneumonia after lung transplantation: Data from a multicenter prospective cohort study.

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

Donor-derived human herpesvirus 8 and development of Kaposi sarcoma among 6 recipients of organs from donors with high-risk sexual and substance use behavior.

Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV-8) infection or through donor-derived HHV-8 transmission. We describe 6 cases of donor-derived HHV-8 infection and KS investigated from July 2018 to January 2020. Organs from 6 donors, retrospectively identified as HHV-8-positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of 6 donors had risk factors for HHV-8 infection reported in donor history questionnaires. Fourteen of 22 organ recipients (64%) had evidence of posttransplant HHV-8 infection. Lung recipients were particularly susceptible to KS. Four of the 6 recipients who developed KS died from KS or associated complications. The US opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase the risk of HHV-8 transmission to recipients. Better awareness of the risk of posttransplant KS for recipients of organs from donors with HHV-8 infection risk could be useful for recipient management. Testing donors and recipients for HHV-8 is currently challenging with no validated commercial serology kits available. Limited HHV-8 antibody testing is available through some US reference laboratories and the Centers for Disease Control and Prevention.

A single-institution study of concordance of pathological diagnoses for interstitial lung diseases between pre-transplantation surgical lung biopsies and lung explants.

BACKGROUND: By comparing diagnoses made by pre-transplant surgical lung biopsy (SLB) and the final pathologic diagnosis of the explanted pathology (EP), we aimed to study the factors that could impact pathologic diagnoses in patients with interstitial lung disease (ILD). METHODS: We retrospectively reviewed the lung transplant database at Cleveland Clinic [01/01/2006-12/31/2013] to include all lung transplant recipients with a prior diagnosis of ILD. Two pulmonary pathologists independently reviewed each SLB and lung explant. The diagnoses were labeled as concordant (same diagnosis on SLB and explant) or discordant (diagnosis on SLB and explant were different) by consensus. RESULTS: Of 389 patients transplanted for ILD, 217 had an SLB before transplant. Pathological diagnoses were concordant in 190 patients (87.6%) [165 UIP (86.8%), 13 NSIP (6.8%), 8 CHP (4.2%) and 4 other diagnoses (2.1%). In 27 cases (12.4%), the diagnosis on SLB differed from EP. 8/27 were diagnosed with UIP on SLB and of these, 5 were re-classified as NSIP. 14/19 (73.7%) patients with a SLB diagnosis "other than UIP" were re-categorized as UIP based on explant. Discordant cases had a greater time between SLB and EP than concordant cases (1553 days vs 1248 days). CONCLUSIONS: The pathologic diagnosis of ILD by SLB prior to lung transplant is accurate in most patients, but may be misleading in a small subset of patients. The majority of discordant cases that were reclassified as UIP could be due to a sampling error, or perhaps, an increased time from the date of the SLB to transplant. Future studies examining how multidisciplinary consensus diagnosis affects this discordance are necessary.

Backwash ileitis and the risk of colon neoplasia in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND: The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial. AIM: We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen. METHODS: From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation. RESULTS: Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01-12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92-17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06-9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54-80.9, p = 0.01) was the only factor independently associated with an increased risk. CONCLUSIONS: The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.

Spleen size in idiopathic and heritable pulmonary arterial hypertension.

BACKGROUND: It is unknown whether the spleen size correlates with disease severity and outcome in patients with idiopathic and heritable pulmonary arterial hypertension (PAH). OBJECTIVES: To determine the prevalence of splenomegaly in PAH and assess whether it correlates with severity of disease and outcome. METHODS: We identified subjects with either heritable or idiopathic PAH who had Doppler echocardiography, right-heart catheterization and computed tomography (CT) of the chest and/or abdomen that included the spleen. RESULTS: We included 62 subjects with a mean age (±SD) of 49 (±15) years; 82% were women. Spleen dimensions were 10 (±3), 6 (±2) and 9 (±2) cm for the craniocaudal length, thickness and width measurements, respectively. The median [interquartile range (IQR)] spleen volume was 344 (225-533) cm3. Splenomegaly was observed in 52-63% of the patients, depending on the formula used. The spleen volume was not associated with clinical, echocardiographic or hemodynamic variables. Spleen volume was not associated with adjusted mortality. We studied the characteristics of the spleen during autopsy in 9 patients with idiopathic PAH who died of right-heart failure. The mean (IQR) spleen weight was 220 (151-325) g. We observed early congestion in all but 2 patients who had chronic congestion. CONCLUSIONS: Splenomegaly of predominantly mild degree is common in idiopathic and heritable PAH. However, spleen size was not associated with clinical, echocardiographic, hemodynamic and survival data in these patients.

Thymomas With Intravascular and Intracardiac Growth.

Thymomas are derived from the epithelial component of the thymus and constitute the most common tumor of the anterior mediastinum. These neoplasms are considered malignant for their potential for invasion and metastases. Several histopathologic subclassification schemes have been proposed over the years, however, correlation of histotypes with prognosis remains controversial. In contrast, studies invariably have shown that staging and resection status correlate with oncologic behavior and disease outcomes. In this regard, several staging systems have been presented, though transcapsular invasion and degree of involvement of adjacent anatomic structures are common denominators of all schemes. Involvement of the great vessels and heart most commonly results from direct invasion, which may lead to unusual clinical presentations such as superior vena cava syndrome. Moreover, intravascular and intracardiac growth with or without direct mural invasion rarely occurs. We provide an overview of thymomas with intravascular and intracardiac involvement.

Backwash ileitis does not affect pouch outcome in patients with ulcerative colitis with restorative proctocolectomy.

BACKGROUND & AIMS: There has been controversy over the significance of active inflammation of the terminal ileum (also known as backwash ileitis) in patients with ulcerative colitis (UC) and idiopathic inflammatory bowel disease of indeterminate type for diagnosis and pouch construction. We investigated the impact of backwash ileitis on pouch outcome after restorative proctocolectomy with ileoanal pouch anastomosis. METHODS: Data from patients with backwash ileitis (n = 132) were compared with those from 132 matched controls without ileal inflammation for age, sex, and type of proctocolectomies with ileal pouch construction (1- or 2-stage). We evaluated terminal ileal sections from original colectomies of 2213 patients with either UC or idiopathic inflammatory bowel disease of indeterminate type, collected during a 21-year period, for extent and severity of chronic and active ileitis. Clinical pouch outcomes were assessed through a longitudinally maintained clinical outcome database that systematically catalogued all short-term and long-term pouch complications, including pouchitis, sepsis, impaired long-term pouch survival, and conversion to Crohn's disease. RESULTS: Regardless of severity or extent, backwash ileitis was not correlated with any clinical outcome examined, short-term or long-term. CONCLUSIONS: Ileal inflammation is not a contraindication for restorative proctocolectomy with ileal pouch construction in patients with UC or idiopathic inflammatory bowel disease of indeterminate type. Ileal inflammation with pancolitis is not a useful criterion for classifying otherwise typical UC as colitis of indeterminate type, because pouch outcomes are not affected.

Spontaneous cerebrospinal fluid rhinorrhea as the initial presentation of growth hormone-secreting pituitary adenoma.

Patients with acromegaly usually present with characteristic clinical features or comorbidities associated with excess insulinlike growth factor 1 (IGF-1)/growth hormone (GH) or may come to medical attention secondary to mass effects causing visual field distortions. Herein, we report a case of spontaneous cerebrospinal fluid (CSF) rhinorrhea as the presenting symptom of acromegaly. A 68-year-old man presented to an outside facility with a 2-day history of headache associated with nausea, vomiting, dizziness, and clear nasal discharge and underwent 2 attempted repairs of a sphenoid sinus CSF leak. Examination on admission to our hospital was significant for fluctuating level of consciousness. Subsequently, subtle coarse facial features were appreciated. Pituitary function testing showed thyrotropin and gonadotropin deficiencies along with an elevated age- and sex-matched IGF-1 of 285 (normal level, 59-225 ng/mL). Nadir GH during oral glucose tolerance test was 5.5 ng/mL and confirmed the diagnosis of acromegaly. Magnetic resonance imaging showed pneumocephalus, an enlarged sella with an elongated pituitary stalk, and partial erosion of the anterior wall of the sphenoid sinus. A distinct adenoma could not be identified. An endoscopic, transnasal, transsphenoidal exploration and biopsy with multilayered skull base reconstruction were performed. Histologic examination of the biopsy contents was consistent with a GH-producing adenoma. Postoperatively, the patient's fluctuating level of consciousness improved and returned to baseline after his successful skull base repair. During the follow-up period, he had an IGF-1 of 713 ng/mL and started treatment with a somatostatin analogue. To our knowledge, this is the first reported case of a GH-producing pituitary adenoma presenting with spontaneous CSF rhinorrhea. Pituitary adenomas should be considered in the differential diagnosis of patients presenting with spontaneous CSF rhinorrhea with abnormal sellar image, and these patients should undergo a thorough hormonal evaluation.

The pulmonary pathology of COVID-19.

A growing number of international postmortem studies identify acute and organizing diffuse alveolar damage (DAD) as the main pathologic feature of lung injury in patients with COVID-19. Other forms of acute lung injury, including organizing pneumonia, and acute fibrinous and organizing pneumonia are seen. Acute neutrophilic infiltrates have been observed, most frequently as the manifestation of a superimposed bacterial pneumonia. SARS-CoV-2 has been detected in type I and type II pneumocytes and bronchial epithelial cells using electron microscopy, immunohistochemistry, and in situ hybridization, and likewise, viral transcripts were localized with RNA probes in pneumocytes. However, the presence of true viral cytopathic effect seen with light microscopy remains to be defined. Interestingly, vascular changes are frequently observed in association with DAD, which include severe endothelial injury/endothelialitis, hemorrhage, and thrombotic and microangiopathic vasculopathy. Since similar vascular changes also occur in cases of DAD independent of the etiology, whether the vascular pathology in COVID lungs has unique features and represents a separate pathologic process is under investigation.

Systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. It is a rare condition that affects mostly young and middle-aged women, resulting in disproportionate morbidity and mortality. Currently, interstitial lung disease is the most common cause of death among patients with systemic sclerosis, with a prevalence of up to 30% and a 10-year mortality of up to 40%. Interstitial lung disease is more common among African Americans and in people with the diffuse cutaneous form of systemic sclerosis or anti-topoisomerase 1 antibodies. Systemic sclerosis-associated interstitial lung disease most commonly presents with dyspnoea, cough, and a non-specific interstitial pneumonia pattern on CT scan, with a minority of cases fulfilling the criteria for usual interstitial pneumonia. The standard therapy has traditionally been combinations of immunosuppressants, particularly mycophenolate mofetil or cyclophosphamide. These immunosuppressants can be supplemented by targeted biological and antifibrotic therapies, whereas autologous haematopoietic stem-cell transplantation and lung transplantation are reserved for refractory cases.

Desquamative interstitial pneumonia in a non-smoker with neurofibromatosis type 1 (Von Recklinghausen syndrome).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with multiple systemic manifestations. Pulmonary involvement has been reported in the form of interstitial fibrosis, emphysema, pulmonary hypertension and thoracic neoplasm. We report a case of desquamative interstitial pneumonia in a non-smoker with NF1.

Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping).

OBJECTIVES: The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. METHODS: Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. RESULTS: The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. CONCLUSIONS: The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

E-Cigarette or Vaping Product Use-Associated Lung Injury: A Review for Pathologists.

CONTEXT.­: Vaping is the inhalation of heated aerosol from a small battery-powered device as a method to deliver nicotine or other substances. A recent outbreak of severe respiratory illness primarily in the United States has put a spotlight on vaping and its potential risks. OBJECTIVE.­: To familiarize pathologists with vaping, the cytologic and histopathologic features of vaping-associated acute lung injury, and the role of pathology in this diagnosis. DATA SOURCES.­: A targeted literature review was performed. CONCLUSIONS.­: Most cases of vaping-associated lung injury have been linked to vaping products containing tetrahydrocannabinol or other cannabinoids. Lung biopsies show a spectrum of nonspecific acute lung injury patterns (organizing pneumonia, diffuse alveolar damage, acute fibrinous, and organizing pneumonia, or combinations of the above), accompanied by prominent, foamy macrophage accumulation. Injury is usually accentuated around small airways. Lipid-laden macrophages can be identified in bronchioloalveolar lavage fluid in most patients and these can be highlighted using lipid stains, such as oil red O, but the clinical utility of this finding remains unclear, as lipid-laden macrophages can be seen in a wide variety of processes and should not be relied upon to make the diagnosis. Classic histologic features of exogenous lipoid pneumonia have not been identified in tissue samples. Lightly pigmented macrophages, similar to those seen with traditional cigarette smoking, are present in some cases but are usually a minor feature. To date, no specific pathologic features for vaping-related injury have been identified, and it remains a diagnosis of exclusion that requires clinicopathologic correlation.

Pulmonary Pathology in Rheumatic Disease.

The pathology of the pulmonary manifestations of rheumatoid diseases is characterized by its histologic heterogeneity and overlap with other pulmonary diseases. All anatomic compartments are vulnerable; thus, the morphologic changes vary according to the predominant region involved. Furthermore, the histologic patterns of injury are not unique to rheumatic diseases, given their resemblance to those seen in idiopathic forms, or in lung disease associated with other conditions. The patterns of interstitial lung disease, airway disorders, pleural processes, and vascular manifestations are described. The histopathology of selected entities, including the main vasculitides affecting the lung, and Ig G4-related disease are discussed.