Executive Summary Objectives Participants Evidence Validation Key Messages Introduction Rationale for a Change in the Approach to Classification of Idiopathic Interstitial Pneumonias Development of a New Classification of Idiopathic Interstitial Pneumonia Current Classification of IIP New ATS/ERS Classification Principles Guiding the Assessment of Patients with Idiopathic Interstitial Pneumonias The Diagnostic Process Is Dynamic Clinical Evaluation Radiological Evaluation Role of Surgical Lung Biopsy Unclassifiable Interstitial Pneumonia Bronchoalveolar Lavage Fluid Evaluation Idiopathic Pulmonary Fibrosis Clinical Features Radiologic Features Histologic Features IPF: Areas of Uncertainty Nonspecific Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features NSIP: Areas of Uncertainty Cryptogenic Organizing Pneumonia Clinical Features Radiologic Features Histologic Features COP: Areas of Uncertainty Acute Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features AIP: Areas of Uncertainty Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical Features Radiologic Features Histologic Features RB-ILD: Areas of Uncertainty Desquamative Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features DIP: Areas of Uncertainty Lymphoid Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features LIP: Areas of Uncertainty References Appendix

American thoracic society/European respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias

Pathology and genetics of tumours of the urinary system and male genital organs

Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases. Idiopathic pulmonary fibrosis (or cryptogenic fibrosing alveolitis) (IPF or CFA) is one of several idiopathic interstitial pneumonias. IPF is now recognized as a distinct clinical disorder. Despite major accomplishments in our understanding of the pathogenesis of lung fibrosis (l), the diagnosis and management of patients with IPF continues to pose significant challenges (24).

Idiopathic pulmonary fibrosis : Diagnosis and treatment. International consensus statement

Background Pathologic Classification of Idiopathic Pulmonary Fibrosis UIP DIP/Respiratory Bronchiolitis Interstitial Lung Disease (RBILD) AIP NSIP Clinical Features of the Idiopathic Interstitial Pneumonias UIP DIP/RBILD AIP N SIP Grading of “Cellularity” and Fibrosis Relationship of UIP and DIP Relationship of AIP and UIP Significance of NSIP—A Specific Disease or a Histologic Manifestation of Many Diseases? Summary and Conclusions

Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.

Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance. The study group consisted of 54 men and 50 women with a median age of 63 yr. Median survival was 3.8 yr after diagnosis by OLB with an estimated 10 yr survival of 27%. Current histopathologic review showed a heterogeneous group including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia/fibrosis (NSIP), acute interstitial pneumonia (AIP), bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), and others. Median survival of the UIP group was 2.8 yr which is significantly worse (p < 0.001) than for other subgroups of chronic interstitial pneumonias. IPF includes several histopathologic subgroups with significantly different survival rates. Patients with UIP have worse survival than patients with other types of idiopathic chronic interstitial pneumonias including NSIP. Accurate histopathologic classification is essential for prognostication in patients with IPF.

Prognostic Significance of Histopathologic Subsets in Idiopathic Pulmonary Fibrosis

Eight cases of acute interstitial pneumonia were studied to define the clinical and pathologic features and to determine the relationship to chronic interstitial pneumonia. Clinically, this disease differs from the chronic interstitial pneumonias by a sudden onset and a rapid course. Five patients died of respiratory failure after 23 days to 2 months, and two died of other complications after 3 1/2-6 months. An etiologic agent could not be identified in any case. The histologic hallmark was interstitial fibrosis and edema associated with type II pneumocyte hyperplasia. The fibrosis differed from that seen in the chronic interstitial pneumonias by extensive fibroblast proliferation and relatively little collagen deposition. Autoradiographic studies of tritiated thymidine (3H-TdR) uptake showed high labeling indices in interstitial cells and type II pneumocytes. Evidence of acute lung injury, including both endothelial and epithelial cell damage, was a prominent ultrastructural feature. These findings emphasize that acute interstitial pneumonia is a clinically and pathologically distinct form of interstitial pneumonia that should be separated from the group of chronic interstitial pneumonias.

Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study

Five unusual polypoid lesions of the endometrium which we term atypical polypoid adenomyomas are described; these growths occurred in premenopausal women. Each of the polyps was characterized by irregular atypical glands with squamous metaplasia and a cellular, smooth muscle mesenchyme, having a pattern to be distinguished from infiltrating adenocarcinoma or a malignant mixed mullerian tumor. Electron microscopy in one case confirmed the presence of a well-differentiated smooth muscle component. These lesions were focal and noninvasive. Two of the three patients who had hysterectomies has small residual lesions confined to the endometrium. Follow-up from 4 to 24 months showed no recurrence. One patient had a second D & C reported as normal; she subsequently became pregnant. The benign behavior of these unusual polyps suggests that atypical adenomyomas can be managed conservatively in the premenopausal woman without the necessity of a hysterectomy.

Atypical polypoid adenomyomas of the endometrium

In reviewing all proliferative serous tumors of the ovary seen at Barnes Hospital from 1950 to 1974, we quantitated histologic characteristics and defined criteria for diagnosis in 55 borderline tumors, 13 well-differentiated cystadenocarcinomas, and 15 cystadenomas with unusual proliferative areas. This last type with focal proliferation behaved in a benign fashion and should be considered a variant of a simple cystadenoma. Stromal invasion was the only histologic feature which consistently distinguished carcinomas from the borderline tumors. The presence in some borderline tumors of severe cellular atypia, marked epithelial disorganization, frequent mitoses, and cribriform glands in the stroma neither signified carcinoma nor indicated poor prognosis. No patient with a Stage I borderline lesion died of tumor. Although the mortality of patients with Stage IIb or Stage III borderline tumors is high, tumor-related deaths rarely occurred before 5 years, and three patients lived more than 10 years. Borderline serous tumors are low-grade malignant neoplasms which differ from overt carcinomas in the excellent prognosis of Stage I lesions and in long survival even with widespread abdominal disease.

Proliferative serous tumors of the ovary. Histologic features and prognosis.

The fine structure of 26 metastatic melanomas, including 13 pigmented and 13 amelanotic tumors, was studied to define ultrastructural criteria for diagnosis. Several important features in addition to melanosome granules were identified. Dendritic cytoplasmic processes were seen in 25 of the 26 cases, cell clusters formed by concentric aggregates of several cells and their processes were present in 18, and microvilli were found on cell surfaces in all cases. The cytoplasm was complex, containing numerous mitochondria, Golgi systems, endoplasmic reticulum, nonspecific filaments, and microtubules. Nuclear morphology was variable. Basement membranes and cell junctions including desmosomes were often encountered, and some melanomas shared features with Schwann cells, including complex membrane interdigitations. All tumors contained melanosomes, although the classic forms were frequently difficult to identify and abnormal variant forms often predominated. Knowledge of the variant melanosome morphology and an un...

Metastatic melanoma: the spectrum of ultrastructural morphology.

We investigated seven uterine wall lesions, selected because of the presence of unexpected patterns or components, to determine their relationship to normal uterine constituents. These lesions included a bizarre leiomyoma, a palisading leiomyoma which resembled a schwannoma, two myxomas, irradiated myometrium, a plexiform tumor, and a leiomyoma with tubular structures. All of these lesions except for the epithelial component of the plexiform tumor showed ultrastructural characteristics of smooth muscle, demonstrating a common origin from the myometrium. Two tumors, the plexiform tumor and the leiomyoma with tubules, had the pattern of epithelial structures suggesting origin from mullerian mesencyme: the plexiform tumor resembled incompletely differentiated endometrium and the tubular structures in the leiomyoma had features of mesothelium. We conclude that these varied and often confusing morphologic patterns reflect the capacity of uterine smooth muscle and stroma to undergo a wide spectrum of alterations including differentiation toward epithelial structures. Changes of this type occur in benign and malignant uterine stromal neoplasms and do not in themselves have prognostic significance.

Michael T. Mazur

Papers

Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study

Atypical polypoid adenomyomas of the endometrium

Proliferative serous tumors of the ovary. Histologic features and prognosis.

Metastatic melanoma: the spectrum of ultrastructural morphology.

Histogenesis of morphologic variations in tumors of the uterine wall.