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.

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.

Pulmonary Manifestations of Systemic Sclerosis and Mixed Connective Tissue Disease.

Systemic sclerosis (SSc) is a rare disease characterized by widespread collagen deposition resulting in fibrosis. Although skin involvement is the most common manifestation and also the one that determines the classification of disease, mortality in SSc is usually a result of respiratory compromise in the form of interstitial lung disease (ILD) or pulmonary hypertension (PH). Clinically significant ILD is seen in up to 40% of patients and PH in up to 20%. Treatment with either cyclophosphamide or mycophenolate has been shown to delay disease progression, whereas rituximab and lung transplantation are reserved for refractory cases.

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.

Broncholithiasis: A Review.

The term "broncholithiasis" is defined as the presence of calcified or ossified materials within the tracheobronchial tree. The report of the condition dates back to 300 bc when Aristotle first described a symptom of "spitting of stones." The process of calcification usually starts within either the mediastinal, hilar, or peribronchial lymph nodes. The impetus is typically initiated by a granulomatous process such as TB or histoplasmosis; however, it can also been seen following exposure to other fungal or occupational elements. The exact mechanism of the calcified material (broncholith) entering the endobronchial tree remains unknown. It is hypothesized, however, that the calcified tissues gradually erodes and/or breaks loose in the airways as a result of repetitive movements of respiration or cardiac pulsations. The broncholiths are often found in the airways without any signs of erosion, however. The most common symptoms of broncholithiasis include cough, hemoptysis, and wheezing as a result of irritation of the airways and the surrounding tissues. The diagnosis is typically suspected on chest radiographs and confirmed by using bronchoscopy. Depending on the severity of the disease, management options range from simple observation to surgical resection. Despite the potential for major complications, the overall disease prognosis is good if timely and appropriate management is provided.

Does Strong and Diffuse PAX-8 Positivity Occur in Primary Lung Carcinoma? An Immunohistochemical Study of 418 Cases and Review of the Literature.

Although rare cases of PAX-8-positive primary lung carcinoma have been reported, details of staining distribution and intensity in such cases are limited. The aim of this study was to determine whether strong and diffuse PAX-8 staining can occur in primary lung carcinoma. Immunohistochemical staining for PAX-8 (Rabbit polyclonal, 10336-1-AP; Proteintech) was performed on whole-tissue sections from 418 resected primary lung carcinomas. PAX-8 was positive in 5/418 (1.2%) cases, all of which were large cell neuroendocrine carcinomas. Staining was weak to moderate in all 5 cases, and was seen in 5% to 30% of tumor cells. All other primary lung carcinomas (413/418) were negative for PAX-8. This study-the largest series of PAX-8-stained whole-tissue sections of primary lung carcinoma to date-shows that strong and diffuse staining for PAX-8 does not occur in primary lung carcinoma of any type. This staining pattern in a carcinoma in a lung specimen provides strong evidence of nonpulmonary origin.

A 42-Year-Old Woman With Abnormal Chest CT Scan and Chylous Ascites.

A 42-year-old white woman presented to the pulmonary clinic for evaluation of abnormal chest imaging. Twenty years prior to presentation, she was noted to have an abnormal chest radiograph during a routine preemployment evaluation. A subsequent bronchoscopy was nondiagnostic. She was followed up with annual imaging, which demonstrated little or no progression of her disease. She remained symptom free throughout this period. A year before her visit to the pulmonary clinic, she developed abdominal discomfort and was found to have ascites. Subsequently, she underwent three paracenteses with analysis revealing chylous fluid. She was a nonsmoker without a history of exposures or travel.

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.

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.