Biomedical subjects
Jeffrey L Myers
Publications and source records attributed to Jeffrey L Myers.
Organizing pneumonia in patients with hematologic malignancies: a steroid-responsive lesion.
BACKGROUND: Organizing pneumonia (OP) is a distinct histopathologic lesion that occurs in a variety of clinical contexts. There have been occasional reports of OP occurring in patients with hematologic malignancies. STUDY OBJECTIVES: To examine the association of OP with hematologic malignancies and to assess the clinical course of affected patients. DESIGN: A retrospective review of our institutional experience of unexplained OP developing in patients with hematologic malignancies. SETTING: Tertiary care, referral medical center. PATIENTS: We identified 6 patients with a verified histopathologic diagnosis of OP and antecedent or concomitant diagnosis of a hematologic malignancy from the Mayo Clinic database (1995-2003). Clinical, radiologic, and outcome data were abstracted from records. RESULTS: Underlying hematologic disorders included lymphoma (2), acute leukemia (2), cutaneous T-cell lymphoma (1), and myelodysplastic syndrome (1). OP was diagnosed by surgical lung biopsy in 4 and bronchoscopic biopsy in 2. Four of the 6 patients had previously been exposed to chemotherapeutic agents, two had not. Three of the 6 patients had bone marrow transplantation prior to development of OP. Five patients were treated with prednisone and all experienced symptomatic improvement with documented radiologic resolution in 4. One patient experienced symptomatic and radiologic resolution with observation alone. Three patients ultimately died from complications of their underlying hematologic disorder and 1 patient died of unknown causes. Two patients were alive without respiratory complaints more than 1 year after lung biopsy. CONCLUSIONS: OP occurs in patients with underlying hematologic malignancies who may or may not have been treated with chemotherapy and responds favorably to corticosteroid therapy.
Formation of the 12q14-q15 amplicon precedes the development of a well-differentiated liposarcoma arising from a nonchondroid pulmonary hamartoma.
Pulmonary hamartoma is a benign neoplasm that rarely recurs or undergoes malignant transformation. Herein, we report a 48-year-old woman with a history of an incomplete excised nonchondroid pulmonary hamartoma presenting as an indolent tumor recurrence. Excision of the tumor revealed a well-differentiated liposarcoma arising from the hamartomatous component. Fluorescence in situ hybridation analysis for HMGA2 and MDM2 was performed on both hamartomatous and liposarcomatous component. MDM2 and HMGA2 amplification were found in a subset of stromal cells in the hamartomatous component and in most cells of the well-differentiated liposarcoma. No rearrangement HMGA2 was found in the pulmonary hamartoma component. These findings suggest that the formation of the 12q14-q15 chromosome amplicon, the characteristic cytogenetic finding of well-differentiated liposarcomas and the structural genomic component of the supernumerary ring and giant rod chromosomes, occurred before the morphologic changes characteristic of these malignant adipose tissue tumors and likely represents a very early molecular event in their development.
Diffuse alveolar damage: uncommon manifestation of pulmonary involvement in patients with connective tissue diseases.
BACKGROUND: Diffuse alveolar damage (DAD) is a relatively common finding on surgical lung biopsy and can result from a variety of causes. METHODS: We studied nine consecutive patients with connective tissue disease (CTD) and DAD diagnosed on surgical lung biopsy to examine this association and clinical implications. RESULTS: The median age was 63 years (range, 35 to 76 years), and seven of the patients were women (78%). Underlying CTDs included rheumatoid arthritis in five patients, polymyositis in two patients, and one patient each with systemic sclerosis and mixed CTD. In seven patients (78%), CTD had been diagnosed before the onset of DAD; six of these patients had a preexisting interstitial lung disease (ILD) related to their CTD. DAD was the presenting manifestation leading to a new CTD diagnosis in two patients (22%). CT of the chest revealed ground-glass opacities and/or consolidation bilaterally with or without honeycombing. In all patients, surgical lung biopsy revealed DAD for which no cause could be identified other than the underlying CTD. Seven patients (78%) were receiving mechanical ventilatory support at the time of the surgical lung biopsy. Four patients (44%) survived to hospital discharge and included one patient with preexisting ILD and all three patients without chronic ILD. CONCLUSION: We conclude that DAD can complicate the clinical course of patients with CTD-related chronic ILD, or can occasionally occur as a presenting manifestation of CTDs. When DAD occurs in patients with CTDs, the outcome appears to be worse for those with preexisting chronic ILD compared to those without ILD.
Interstitial lung disease in primary Sjögren syndrome.
BACKGROUND: Primary Sjögren syndrome (pSS) has been associated with various histologic patterns of interstitial lung disease (ILD). METHODS: We retrospectively identified 18 patients with pSS and suspected ILD who underwent lung biopsies (14 surgical biopsies and 9 bronchoscopic biopsies) at our institution during a 13-year period from 1992 through 2004. Histopathologic findings were analyzed and correlated with radiologic features and outcome. RESULTS: Median age was 62 years (range, 34 to 78 years), and 15 patients (83%) were women. Most patients presented with dyspnea and cough. Chest radiographs demonstrated bilateral infiltrates, and high-resolution CT revealed abnormalities of various types including ground-glass, consolidation, reticular, and nodular opacities. The major histopathologic patterns included nonspecific interstitial pneumonia (NSIP) [five patients], organizing pneumonia (OP) [four patients], usual interstitial pneumonia (UIP) [three patients], lymphocytic interstitial pneumonia (three patients), primary pulmonary lymphoma (two patients), and diffuse interstitial amyloidosis (one patient). In four patients (three with OP and one with amyloidosis), the diagnosis was established on transbronchial biopsy results. Treatment commonly included prednisone with or without another immunosuppressive agent. During the follow-up period (median, 38 months), most patients improved or remained stable except three patients with UIP, one patient with NSIP, and one patient with amyloidosis. Seven patients (39%) died, including three deaths from acute exacerbation of interstitial pneumonia. CONCLUSIONS: A variety of histologic patterns can be seen in patients with pSS-associated ILD. Those with UIP tended to have progression of lung disease. Death from acute exacerbation of interstitial pneumonia may occur in patients with pSS-associated ILD.
Bronchiolitis: the pathologist's perspective.
The term "bronchiolitis" refers to a broad morphologic spectrum of inflammatory events that are centered on small conducting airways. Bronchiolitis may be an isolated pathologic finding, although it is often a secondary consequence of diseases affecting other parts of the conducting apparatus or pulmonary acinus. Divergent causes of bronchiolitis may have similar microscopic findings. Hence, a pathologic diagnosis is nonspecific and not clinically meaningful unless placed in the context of relevant clinical and radiographic findings. Etiologically, most cases of bronchiolitis are infectious in nature or related to smoking. Increasingly, other causes of bronchiolitis have been recognized, including collagen vascular disease, idiopathic inflammatory bowel disease, or toxins/drugs. Many cases are idiopathic. Histologically, most examples of bronchiolitis demonstrate acute inflammation, usually corresponding to viral infection. Other well-defined histologic categories of bronchiolitis include bronchiolitis obliterans, in which there is fibroblast proliferation within airspaces, and follicular bronchiolitis, corresponding to lymphoid hyperplasia with formation of germinal centers. In recent years, several new forms of bronchiolitis have been recognized, including constrictive bronchiolitis, diffuse panbronchiolitis, and airway-centered fibrosis. This article highlights the clinical and pathologic features of these more recently described entities.
Histologic spectrum of idiopathic interstitial pneumonias.
Histopathologic classification plays a key role in separating multiple forms of idiopathic interstitial pneumonia into clinically meaningful categories with important differences in natural history, prognosis, and treatment. Microscopic criteria in diagnosis of these entities include the pattern and microanatomic distribution of inflammation, fibroblast proliferation, collagen deposition, and architectural remodeling. Usual interstitial pneumonia (UIP) defines idiopathic pulmonary fibrosis and is the most common of the idiopathic interstitial pneumonias. UIP has distinctive morphologic features that allow precise diagnosis in classical cases. Other forms of idiopathic interstitial pneumonia include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, acute interstitial pneumonia, and nonspecific interstitial pneumonia. These latter categories differ from UIP in that the histopathologic findings do not, by themselves, allow specific diagnosis in most cases and require careful correlation with clinical and radiologic findings.
How safe is safe enough? Ask a patient.
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Usual interstitial pneumonia complicating dyskeratosis congenita.
Dyskeratosis congenita (DC) is a rare disorder characterized by skin hyperpigmentation, nail dystrophy, and leukoplakia of mucous membranes. Pulmonary complications occur in approximately 20% of patients, although the specific histopathologic features, the temporal relationship between the diagnosis of DC and the development of pulmonary fibrosis, and the response to specific treatment are largely undefined. We describe 2 patients with DC who developed usual interstitial pneumonia. Pulmonary fibrosis developed 18 and 38 years after the original manifestations of DC. Both patients died of respiratory failure, 4 and 6 months after lung biopsy. Pulmonary fibrosis in patients with DC may be linked to underlying abnormalities of fibroblast function.
Idiopathic pulmonary fibrosis in patients younger than 50 years.
OBJECTIVE: To assess clinical, radiological, histopathologic, and prognostic differences in younger patients with idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS: This study consisted of patients younger than 50 years with IPF who were seen at the Mayo Clinic in Rochester, Minn, from January 1, 1994, to December 31, 2000. Clinical, radiological, and histopathologic data were abstracted from clinical records. Total lung capacity using plethysmography, vital capacity, diffusing capacity for carbon monoxide using the single-breath method, and alveolar volume using single-breath neon wash-in were measured. RESULTS: Our study population was composed of 16 men and 6 women with a median age of 45 years (range, 28-49 years). Median survival was 2.1 years, with 1- and 2-year survival rates of 68% and 53%, respectively. Of the 22 patients, 2 were current smokers, 14 were former smokers, and 6 had never smoked. Three patients had familial pulmonary fibrosis, 21 had bibasilar inspiratory crackles, and 10 had digital clubbing. Median total lung capacity was 56.2%, vital capacity was 51.0%, diffusing capacity was 45.5%, and alveolar volume was 65.0%. CONCLUSION: Although previous studies have suggested that younger age is a favorable prognostic factor in patients with IPF, we found that younger patients have the same poor prognosis as do older patients with this disorder. We observed no distinguishing differences in the clinical, radiological, and histopathologic features compared with those in older patients in whom the disorder is more common. Lung transplantation should be considered early in the treatment of younger patients with IPF.
Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.
BACKGROUND: Desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are uncommon forms of interstitial lung disease and have been incompletely characterized. STUDY OBJECTIVES: To further characterize the clinical features and course of subjects with DIP and RB-ILD. DESIGN: Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS: Twenty-three subjects with DIP and 12 subjects with RB-ILD seen over a 12-year period between 1990 and 2001. INTERVENTIONS: None. RESULTS: The study population included 19 men (54%) and 16 women (46%). The mean (+/- SD) age at diagnosis was 46 +/- 10 and 43 +/- 7 years, respectively, for patients with DIP and RB-ILD. All subjects were either current or previous smokers except for three subjects with DIP. The diagnosis was confirmed in all cases by surgical lung biopsy. Bronchoscopy with transbronchial lung biopsy had been performed in 12 patients and was nondiagnostic in all. The most common pulmonary function abnormality was a reduced diffusing capacity of the lung for carbon monoxide. A CT scan of the chest revealed ground-glass opacities bilaterally in most patients who had DIP and RB-ILD. No differences were observed between subjects with DIP and RB-ILD with respect to clinical features, radiologic findings, or pulmonary function test results. The clinical course was characterized by relative stability in the majority of patients in both groups and a partial response to corticosteroid therapy. Five deaths were observed, including three resulting from progressive diffuse lung disease, all in subjects with DIP. CONCLUSIONS: We concluded that DIP and RB-ILD are chronic disease processes that in most patients are related to smoking. Persistent abnormalities can be seen on pulmonary function testing and radiologic studies despite smoking cessation and corticosteroid therapy. Corticosteroid therapy appeared to be associated with modest clinical benefit but usually not with resolution of disease. Progressive disease with eventual death can occur in subjects with DIP, especially with continued cigarette smoking.
Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy.
STUDY OBJECTIVES: To define the clinicopathologic features and outcome of acute exacerbation in patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy. DESIGN: Retrospective, single-center study. SETTING: Tertiary care, referral medical center. PATIENTS: Seven patients with acute exacerbation of IPF who underwent surgical lung biopsy. RESULTS: The median age of these seven patients was 70 years (range, 59 to 74 years); two were women. Five patients had a smoking history and included two current smokers. All patients were experiencing an exacerbation of dyspnea for a median duration of 14 days (range, 7 to 28 days) prior to presentation. In three of these patients, the acute deterioration was the presenting feature of IPF, while in the remaining four patients the diagnosis of IPF had previously been established. Chest radiography demonstrated bilateral mixed alveolar-interstitial infiltrates in all of them. CT revealed ground-glass opacities and consolidation bilaterally in all patients with associated peripheral honeycombing in six of them. Echocardiography was performed in six patients and demonstrated pulmonary hypertension in all. BAL fluid was obtained in five patients and revealed neutrophilia in all. Surgical lung biopsy showed diffuse alveolar damage (DAD) in five patients with associated collagen fibrosis and honeycomb changes typical of usual interstitial pneumonia (UIP). One biopsy showed a combination of UIP and organizing pneumonia, while one biopsy showed only DAD. Despite treatment with lung-protective ventilation strategies and high-dose systemic corticosteroids, six patients (86%) died during their hospitalization. CONCLUSIONS: Although IPF is typically associated with an insidious, slowly progressive clinical course, acute exacerbations occur and may be the presenting manifestation in some patients. In either situation, current management strategies including high-dose corticosteroid therapy appear to be relatively ineffective for these patients with acute exacerbation undergoing surgical lung biopsy.
Respiratory epithelium in usual interstitial pneumonia/idiopathic pulmonary fibrosis: spark or destructive flame?
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Malignant basomelanocytic tumor manifesting as metastatic melanoma.
We report a case of an unusual basomelanocytic tumor from the scalp of a 56-year-old man. A 56-year-old white man presented with a scalp lesion that was biopsied and interpreted as a basal cell carcinoma. Fourteen months later, metastatic melanoma was discovered in a cervical lymph node and the liver. A subsequent biopsy from the area of the previously biopsied basal cell carcinoma of the scalp showed an invasive malignant melanoma. Immunohistochemical stains performed on the original scalp specimen showed biphasic immunohistochemical profile. A population of neoplastic cells was strongly positive for the melanocytic markers Melan-A, HMB-45, and tyrosinase and showed weak focal immunoreactivity for S-100. A second population of cells was strongly immunoreactive for keratin (wide-spectrum polyclonal antibody) and BerEp4. To our knowledge, this is the first description of a malignant basomelanocytic tumor complicated by metastatic melanoma.
Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases.
Amyloid-like pulmonary nodules have been described in patients with systemic light-chain deposition disease, but their significance in other clinical contexts is unknown. We examined biopsy specimens of amyloid-like pulmonary nodules from 3 women without systemic light-chain deposition disease. Patient 1 (aged 62 years) had multiple pulmonary nodules and underwent 2 separate lung biopsies, the first showing nodules composed of kappa light-chain deposits accompanied by low-grade lymphoplasmacytic lymphoma limited to the lung and the second, obtained after chemotherapy 9 months later, showing only residual nodules without persistent lymphoma. Patients 2 (aged 65 years) and 3 (aged 69 years) had asymptomatic solitary pulmonary nodules. In all cases, electron microscopic examination showed dense granular extracellular deposits without the fibrillary characteristics of amyloid. Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.
Tracheal myxoma: a rare benign tracheal tumor.
Benign tracheal tumors are rare. We describe a 39-year-old man who underwent resection of a tracheal myxoma, a previously unrecognized benign tracheal neoplasm. He presented with a 9-month history of wheezing, cough, and dyspnea on exertion. Treatment with bronchodilators and corticosteroids administered by inhalation and systemically did not diminish his symptoms. Pulmonary function tests showed a pattern of airflow limitation consistent with variable extrathoracic obstruction. Chest radiography and computed tomography revealed a tracheal mass. Tracheal resection of the tumor with reconstruction was curative. The patient is free of disease 7 years after surgery.
Bronchiolar disorders.
Bronchiolar abnormalities are relatively common and occur in a variety of clinical settings. Various histopathologic patterns of bronchiolar injury have been described and have led to confusing nomenclature with redundant and overlapping terms. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Herein, we present a scheme separating (1) those disorders in which the bronchiolar disease is the predominant abnormality (primary bronchiolar disorders) from (2) parenchymal disorders with prominent bronchiolar involvement and (3) bronchiolar involvement in large airway diseases. Primary bronchiolar disorders include constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans), acute bronchiolitis, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust airway disease, follicular bronchiolitis, and a few other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia), and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical relevance of a bronchiolar lesion is best determined by identifying the underlying histopathologic pattern and assessing the correlative clinico-physiologic-radiologic context.
Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers.
BACKGROUND: BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS: The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS: The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS: The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.