Background

Second hand smoke has brought the issue of cigarette smoking and lung cancer to the forefront.  It is amazing the degree to which the lung is involved in many diseases.  A terminal pneumonia is often the final death blow in a chronically ill patient.  Biopsies of lung tumors often present a diagnostic dilemma for the pathologist.  Many metastatic cancers to the lung may resemble primary lung cancers.  The pathologist has a battery of immunohistochemical stains which can greatly aid in the diagnosis.  By discerning whether a tumor is primary or secondary, appropriate treatment may begin.  Open lung biopsies are performed by the surgeon often to evaluate chronic interstitial lung diseases. This group of diseases may have their origin in chemical or occupational exposure, hypersensitivity reactions to allergens or drugs, or most often, of unknown or idiopathic causes. The pathologist correlates the biopsy findings with the radiologic and clinical presentation of the patient.

Another type of biopsy known as a transbronchial biopsy (TBB) is also increasingly utilized by pulmonologists to take biopsies of the lung. The challenge for the pathologist is to determine the adequacy of the biopsy as well as to determine whether an actual diagnosis can be made. Various definitions of adequacy have been proposed. Katzenstein suggests that a biopsy be viewed as adequate if at least one fragment of alveolated parenchyma is present. However, there are diseases where alveoli may not be present and a diagnosis may still be established. Sarcoidosis with noncaseating granulomas is one example. TBB is an excellent diagnostic procedure for some malignancies, infections, sarcoidosis (as high as 90% in some reports), and acute transplant rejection.

It is not a good procedure for diseases where the low power microscopic survey of the tissue is critical. These include diseases with interstitial inflammation, fibrosis, air space granulation tissue, air space macrophages, and reactive alveolar lining cells (i.e., idiopathic interstitial pneumonias and morphologically related conditions). A recent joint consensus statement of the American Thoracic Society and the European Respiratory Society on idiopathic interstitial fibrosis states that ``transbronchial biopsies are not helpful in making the diagnosis of UIP.''

Churg-Strauss Syndrome (Allergic Angiitis and Granulomatosis)
Congenital Cystic Adenomatoid Malformation
Diffuse Alveolar Damage (ARDS, Adult Respiratory Distress Syndrome)
Emphysema
Interstitial Lung Disease (Pneumonitis, DIP, UIP)
Lung Cancer
Lymphangiomyomatosis (LAM)
Lymphoid Interstitial Pneumonitis (LIP)
Neuroendocrine Carcinoma (Including Carcinoid, Atypical Carcinoid Tumors, and Small Cell/Oat Cell Carcinoma)
Pleural Effusion
Pneumoconiosis
Pulmonary Alveolar Proteinosis
Pulmonary Blastoma
Pulmonary Hypertension
Pulmonary Sclerosing Hemangioma
Sarcoidosis
Solitary Fibrous Tumor of the Pleura
Transfusion Related Acute Lung Injury (TRALI)

OUTLINE

Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Commonly Used Terms
Internet Links

LABORATORY/ RADIOLOGIC/OTHER	CHARACTERIZATION
Interpretation of tissue artifacts in transbronchial lung biopsy specimens. Kendall DM, Gal AA. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.	Ann Diagn Pathol 2003 Feb;7(1):20-4 Abstract quote Proper interpretation of transbronchial biopsies is critical for appropriate patient management. Artifacts in lung tissue acquired during the biopsy procedure or subsequent processing may mimic "true" disease and potentially lead to incorrect diagnoses. In this study the interpretation of various artifacts in transbronchial biopsies will be correlated with the level of pathologist training and experience. Minced 1 to 2 mm fragments of normal lung tissue were processed to produce various tissue artifacts (atelectasis, sponge artifact, or bubble artifact). Seven hematoxylin-eosin-stained slides of various artifacts and three similar-appearing slides from "true" pulmonary diseases (lipoid pneumonia, usual interstitial pneumonia, and foreign body reaction) were evaluated by eight pathologists of different levels of training and experience. Most pathologists were unaware of the various artifacts in transbronchial biopsies and were occasionally able to differentiate them from true disease. Senior faculty frequently identified and correctly diagnosed the true pathology slides; however, they often failed to recognize artifacts. Junior faculty performed the best by correctly identifying the majority of true pathology and dismissed most artifacts. Junior and senior residents described the microscopic changes, but had more difficulty determining the significance of both true pathology and artifacts. Various artifacts in transbronchial biopsy specimens can create diagnostic dilemmas for all pathologists regardless of level of training. The elimination of these artifacts should reduce the possibility of biopsy misinterpretation.
Estimation of Performance and Sequential Selection of Diagnostic Tests in Patients With Lung Lesions Suspicious for Cancer Dana Marie Grzybicki, MD, PhD, Thomas Gross, MD, Kim R. Geisinger, MD, and Stephen S. Raab, MD From the Department of Pathology and Laboratory Medicine, Allegheny General Hospital and MCP Hahnemann University, Pittsburgh, Pa (Drs Grzybicki and Raab); the Department of Internal Medicine, University of Iowa College of Medicine, Iowa City (Dr Gross); and the Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC (Dr Geisinger).	Arch Pathol Lab Med 2002;126, No. 1, pp. 19–27. Abstract quote Context.—Measuring variation in clinician test ordering behavior for patients with similar indications is an important focus for quality management and cost containment. Objective.—To obtain information from physicians and nonphysicians regarding their test-ordering behavior and their knowledge of test performance characteristics for diagnostic tests used to work up patients with lung lesions suspicious for cancer. Design.—A self-administered, voluntary, anonymous questionnaire was distributed to 452 multiple-specialty physicians and 500 nonphysicians in academic and private practice in Pennsylvania, Iowa, and North Carolina. Respondents indicated their estimates of test sensitivities for multiple tests used in the diagnosis of lung lesions and provided their test selection strategy for case simulations of patients with solitary lung lesions. Data were analyzed using descriptive statistics and the 2 test. Results.—The response rate was 11.2%. Both physicians and nonphysicians tended to underestimate the sensitivities of all minimally invasive tests, with the greatest underestimations reported for sputum cytology and transthoracic fine-needle aspiration biopsy. There was marked variation in sequential test selection for all the case simulations and no association between respondent perception of test sensitivity and their selection of first diagnostic test. Overall, the most frequently chosen first diagnostic test was bronchoscopy. Conclusions.—Physicians and nonphysicians tend to underestimate the performance of diagnostic tests used to evaluate solitary lung lesions. However, their misperceptions do not appear to explain the wide variation in test-ordering behavior for patients with lung lesions suspicious for cancer.

 

DISEASE VARIANTS	CHARACTERIZATION
BLACK SPOTS ON PLEURA
'Black Spots' and hyaline pleural plaques on the parietal pleura of 150 urban necropsy cases. Mitchev K, Dumortier P, De Vuyst P	Am J Surg Pathol 2002 Sep;26(9):1198-206 Abstract quote The absence of any direct connection between the lung and the parietal pleura raises questions about the mechanisms of pleural migration and retention of inhaled particles. It has been suggested that specific areas of parietal pleura absorb and retain inorganic particles from the pleural space, including carbon pigments and asbestos fibers, and could be starting points for pathologic changes induced by mineral fibers. These particle-collecting structures have been called "black spots." To study their distribution, macroscopic appearance, and possible relationship with pleural plaques, the parietal pleura of 150 consecutive necropsies of urban dwellers (mean age 67.7 +/- 12.9 years) were examined. The size and intensity of spots were scored and recorded on a computer scheme together with information of the presence of pleural plaques. Black spots were observed in 92.7% of the cases. They were mainly located in the lower costal and diaphragmatic zones and could correspond to the anatomic distribution of structures involved in pleural cavity clearance. Scores correlated with sex and age. There was no relationship between the predominant locations of black spots and hyaline pleural plaques.
HIGH-ALTITUDE PULMONARY EDEMA
Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor. Swenson ER, Maggiorini M, Mongovin S, Gibbs JS, Greve I, Mairbaurl H, Bartsch P. Pulmonary and Critical Care Section, S-111-Pulm, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108	JAMA 2002 May 1;287(17):2228-35 Abstract quote CONTEXT: The pathogenesis of high-altitude pulmonary edema (HAPE) is considered an altered permeability of the alveolar-capillary barrier secondary to intense pulmonary vasoconstriction and high capillary pressure, but previous bronchoalveolar lavage (BAL) findings in well-established HAPE are also consistent with inflammatory etiologic characteristics. OBJECTIVES: To determine whether inflammation is a primary event in HAPE and to define the temporal sequence of events in HAPE. DESIGN, SETTING, AND PARTICIPANTS: Case study from July through August 1999 of 10 subjects with susceptibility to HAPE and 6 subjects resistant to HAPE, all of whom are nonprofessional alpinists with previous mountaineering experience above 3000 m. MAIN OUTCOME MEASURES: Pulmonary artery pressure measurements and BAL findings at low altitude (490 m) and shortly before or at the onset of HAPE at an altitude of 4559 m. RESULTS: Subjects who were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P =.004). Despite development of HAPE in the majority of HAPE-susceptible subjects, there were no differences in BAL fluid total leukocyte counts between resistant and susceptible subjects or between counts taken at low and high altitudes. Subjects who developed HAPE had BAL fluid with high concentrations of plasma-derived proteins and erythrocytes, but there was no increase in plasma concentrations of surfactant protein A and Clara cell protein. The chest radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of the HAPE-susceptible group was lavaged before edema was apparent on radiographs. However, 6 subjects from the HAPE-susceptible group who developed HAPE on the following day had a score on bronchoscopy of 1.5, which increased to 4.6, reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites. CONCLUSIONS: Early HAPE is characterized by high pulmonary artery pressures that lead to a protein-rich and mildly hemorrhagic edema, with normal levels of leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary edema with altered alveolar-capillary permeability.
NODULAR LESIONS IN BONE MARROW TRANSPLANT PATIENTS
Pulmonary Nodular Lesions in Bone Marrow Transplant Recipients Impact of Histologic Diagnosis on Patient Management and Prognosis H. Evin Gulbahce, MD, Stefan E. Pambuccian, MD, Jose Jessurun, MD, Paul Woodard, MD, Marie E. Steiner, MD, J. Carlos Manivel, MD, Stephen Hite, MD, Norma K.C. Ramsay, MD, and K. Scott Baker, MD	Am J Clin Pathol 2004;121:205-210 Abstract quote Bone marrow transplantation is associated with numerous pulmonary complications, which may manifest as nodules. We studied 33 bone marrow transplant (BMT) recipients in whom pulmonary nodular lesions (PNLs) developed during a 5-year period and who underwent open lung biopsy (OLB) for diagnosis. Of 33 patients with PNL, 15 (45%) had pulmonary cytolytic thrombi (PCT), a recently described condition characterized histologically by occlusive vascular lesions and hemorrhagic infarcts and clinically by a favorable outcome. Clinical symptoms and radiologic abnormalities disappeared during a period of a few weeks. None of the patients died of PCT; 10 were alive at last contact. The second most common cause of PNL (8/33 [24%]) was Aspergillus infection, which was the cause of death in 6. OLB is an effective way of obtaining diagnostic tissue in BMT recipients with PNLs. Histologic examination is accurate in determining the cause of PNLs and identifying lesions that have a favorable outcome and those that require a change in treatment.
PLACENTAL TRANSMOGRIFICATION
Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a case report and review of the literature. Marchevsky AM, Guintu R, Koss M, Fuller C, Houck W, McKenna RJ. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif, USA.	Arch Pathol Lab Med. 2005 May;129(5):686-9. Abstract quote   Swyer-James (MacLeod) syndrome is an acquired form of unilateral hyperlucency of the lung and is characterized by the development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. It may develop as a complication of repeated episodes of pulmonary infection resulting in bronchiolitis obliterans and obstruction of small airways. Most patients with Swyer-James (MacLeod) syndrome can be managed clinically, and the pathologic features of the syndrome have been described in only a few reports. Placental transmogrification of the lung is a rare histopathologic finding that has been described in patients with severe emphysema associated with cigarette smoking, congenital bullous emphysema, and fibrochondromatous hamartomas of the lung and is characterized by the development of peculiar structures in the pulmonary parenchyma that resemble placental villi. To our knowledge, placental transmogrification of the lung has not been previously described in patients with Swyer-James (MacLeod) syndrome. We encountered a 32-year-old man with a history of childhood asthma who presented with progressively severe exertional dyspnea and had unilateral right lung hyperlucency. The patient underwent a right pneumonectomy. Examination of the lung revealed severe mixed centriacinar-panacinar emphysema in all lobes, bullous emphysema in the upper lobe, bronchiectases, mild interstitial pneumonia with fibrosis, and placental transmogrification of the pulmonary parenchyma of all 3 lobes. Here, we review the pathology of Swyer-James (MacLeod) syndrome and the possible pathogenesis of villous-like changes in the lung tissues.
Placental transmogrification of the lung: clinicopathologic, immunohistochemical and molecular study of two cases, with particular emphasis on the interstitial clear cells. Cavazza A, Lantuejoul S, Sartori G, Bigiani N, Maiorana A, Pasquinelli G, Paci M, Rossi G. Operative Unit of Pathology, S. Maria Nuova Hospital, Reggio Emilia, Italy.	Hum Pathol. 2004 Apr;35(4):517-21. Abstract quote   Two cases of placental transmogrification of the lung are reported. The lesions presented in the left lung, in one case as a giant bulla of the upper lobe and in the other as a cystic nodule of the lower lobe. A segmentectomy was performed in both cases, and the patients were alive and well 5 years and 2 months after surgery, respectively. In our opinion, pulmonary placental transmogrification is not a variant of emphysema, as generally considered, but rather probably represents a benign proliferation of immature interstitial clear cells with secondary cystic change. This report presents a histological, immunohistochemical, ultrastructural and molecular study of these peculiar cells, together with a review of the literature.
Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma. Xu R, Murray M, Jagirdar J, Delgado Y, Melamed J. Department of Pathology, New York University School of Medicine, New York, NY.	Arch Pathol Lab Med 2002 May;126(5):562-6 Abstract quote Context.-Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. Objectives.-To study the relationship between placental transmogrification and pulmonary hamartomas. Design and Methods.-Reports of 38 cases of pulmonary hamartomas during 18 years (1982-1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. Results.-Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit-positive cells were mast cells and not stem cells. Conclusions.-Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.

 

HISTOPATHOLOGY	CHARACTERIZATION
GENERAL
Intrapulmonary airways visualized by staining and clearing of whole-lung sections: the transparent human lung. Monforte-Munoz H, Walls RL. 1Division of Anatomic Pathology, Childrens Hospital Los Angeles, University of Southern California-Keck School of Medicine, Los Angeles, CA, USA.	Mod Pathol. 2004 Jan;17(1):22-7. Abstract quote   Methods for the study of cartilaginous airways represent technically very laborious and time-consuming procedures, many of these with the inevitable disruption or elimination of the distal bronchi and bronchioles. We describe and illustrate a methodology to demonstrate the cartilaginous support of the most distal intrapulmonary airways in hemisections or slabs of whole-, fixed-lung specimens. By this process, the cartilaginous framework of intrapulmonary air passages is highlighted and their outlines are defined. An important and distinct benefit of our procedure is the preservation of the alveolar parenchyma, vasculature and pleura, serving as an anatomic structural context. This improved methodology is based on procedures used in the past, now applied to entire half-sections or slabs of lungs, stained with toluidine blue, subsequent removal of stain from noncartilaginous elements and finally clearing of the specimen. The procedure takes 7-8 days but with limited technical - manual involvement. The resulting specimens demonstrate a highly complex, variable and at times, even unpredictable distribution of cartilage throughout the bronchial anatomy. This method represents a practical way of studying intact, this vital component of the respiratory tract. It also allows assessment of the potential implication of these critical smaller pathways in pathologic conditions, where thus far they have been under-studied.
CYTOLOGY
Diagnostic Sensitivity of Bronchoalveolar Lavage versus Lung Fine Needle Aspirate. Clark BD, Vezza PR, Copeland C, Wilder AM, Abati A. Cytopathology ServiceLaboratory of Pathology, National Cancer Institute/National Institutes of Health (BDC, CC, A-MW, AA), Bethesda, Maryland.	Mod Pathol 2002 Dec;15(12):1259-65 Abstract quote Bronchoalveolar lavage (BAL) and lung fine-needle aspirate (LFNA) are commonly performed as the first line of investigation for a myriad of pulmonary problems associated with abnormal imaging findings (mass, cavitary lesion, infiltrates, etc.). The relative sensitivities of these two procedures are not well established for cytologic diagnosis of lesions for any single disease event. Records were searched for single pulmonary disease events with closely timed BAL and LFNA, as defined by both procedures occurring within </=8 days of each other. No samples with "unsatisfactory" diagnoses were considered for the analyses. Success of identifying malignancy and/or an infectious agent was recorded for both procedures. Between January 1989 and June 2000, 52 episodes of closely timed (65% within 3 d) BAL and LFNA procedures were identified in 45 patients for a single disease event. The clinical scenarios as per the sample requisitions were as follows: consolidation/infiltrate (60%), mass/nodule (23%), cavitary lesion (5.7%), pneumonia (5.7%), or not specified (5.7%). For all cases examined (n = 52), in 18 (35%) of the episodes, LFNA uniquely identified either malignancy, 6/18 (12%), or infectious agents such as Aspergillus and acid-fast bacteria, 12/18 (23%), with a corresponding nondiagnostic BAL. In one episode with a clinical diagnosis of infiltrates, the BAL was positive for acid-fast bacteria, whereas the LFNA was negative. Chi-square analysis of the data revealed statistical significance with P <.0001 with 2 degrees of freedom, indicating LFNA to be a superior method for the diagnosis of pulmonary pathology over BAL. Based on our data, LFNA is the superior method for the cytologic diagnosis of pulmonary pathology amenable to cytologic examination.
EMBOLIZED CROSPOVIDONE
Embolized Crospovidone (poly[N-vinyl-2-pyrrolidone]) in the Lungs of Intravenous Drug Users. Ganesan S, Felo J, Saldana M, Kalasinsky VF, Lewin-Smith MR, Tomashefski JF Jr. Department of Pathology, MetroHealth Medical Center and Case Western Reserve University School of Medicine (SG, JFT) and Cuyahoga County Coroner's Office (JF), Cleveland, Ohio.	Mod Pathol 2003 Apr;16(4):286-92 Abstract quote Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.
ETANERCEPT THERAPY
Pulmonary lymphohistiocytic reactions temporally related to etanercept therapy. Yousem SA, Dacic S. 1The Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.	Mod Pathol. 2005;18:651-655 Abstract quote   This report details the pulmonary pathologic findings in four patients with rheumatoid arthritis, who developed new onset of pulmonary signs and symptoms with alveolar infiltrates temporally related to the institution of etanercept therapy. Biopsy findings showed an interstitial and air space lymphohistiocytic infiltrate with non-necrotizing granulomas, in the setting of negative cultures and special stains for microorganisms. The association with etanercept therapy and granulomatous reactions is discussed along with the differential diagnosis.
MENINGIOMA-LIKE NODULES
Pulmonary Meningothelial-like Nodules: A Genotypic Comparison With Meningiomas Ionescu, Diana N MD; Sasatomi, Eizaburo MD; Aldeeb, Dalal MD; Omalu, Bennet I MD; Finkelstein, Sydney D MD; Swalsky, Patricia A BSC; Yousem, Samuel A MD From the Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, Pennsylvania.	The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 207-214 Abstract quote Background: Minute pulmonary meningothelial-like nodules (MPMNs) are incidental interstitial pulmonary nodules. They share histologic, ultrastructural, and immunohistochemical features with meningiomas (MGs). Design: Sixteen cases yielding 33 separate MPMNs and 10 cases of benign MG were studied. Immunohistochemical studies and mutational analyses were performed on microdissected tissue using 20 polymorphic microsatellite markers targeting 11 genomic regions in an effort to identify genetic similarities of MPMN and MG. Results: A total of 96.6% of MPMNs stained positive for vimentin, 33.3% for epithelial membrane antigen, 3% for S-100, and all were negative for cytokeratin and synaptophysin. Loss of heterozygosity (LOH) was identified in 25% of single MPMN affecting 3 genomic loci. No solitary MPMN had more than 1 LOH event. Multiple LOHs were seen only in MPMN-omatosis syndrome, where 33.3% of MPMNs showed LOH affecting 7 genomic loci. MG showed the highest frequency of LOH with major events seen at 22q (60%), 14q (42.8%), and 1p (44.4%) that were not shared by MPMN. Conclusion: Isolated MPMN lacks mutational damage, consistent with a reactive origin. MPMN-omatosis syndrome might represent the transition between a reactive and neoplastic proliferation. MPMNs are different from MG based on the major molecular genetic events seen in their formation and progression.
MUCINOUS CYSTIC NEOPLASMS
The Spectrum of Pulmonary Mucinous Cystic Neoplasia A Clinicopathologic and Immunohistochemical Study of Ten Cases and Review of the Literature Zu-hua Gao, MD, PhD, FRCPC, and Stefan J. Urbanski, MD	Am J Clin Pathol 2005;124:62-70 Abstract quote We describe 10 new cases and review 66 previously reported cases of primary pulmonary mucinous cystic neoplasia (PMCN). The 3 men and 7 women were 44 to 73 years old (mean, 60.0 years) at diagnosis. Lesions were found by chest radiograph (featuring a solitary, lobulated nodule with soft tissue density that enlarged slowly), or patients had major bronchial occlusion by mucus or hemoptysis. Tumors were well-circumscribed, lobulated soft masses with a central cavity filled with gray to greenish translucent mucus and were 1.5 to 5.5 cm in greatest dimension (mean, 3.3 cm). Microscopically, confluent lakes of mucin characterized all cases. Tumor epithelium ranged from bland to focal cytologic atypia to frankly malignant. The adjacent lung parenchyma was stretched, compressed, or showed an inflammatory reaction to dissected mucin. After 1- to 10-year follow-up (mean, 3.7 years), 3 patients died of metastasis and 1 of amitriptyline toxic effects; 6 were alive without tumor. Combined analysis of our cases and previously reported cases suggests a histologic spectrum from benign cystadenoma to mucinous cystic tumor with atypia to well-differentiated mucinous cystadenocarcinoma. The histomorphologic criteria derived from this analysis can help distinguish PMCN from other types of primary or metastatic mucinous tumors and predict outcome.
SALIVARY GLAND-LIKE TUMORS IN HAMARTOMAS
Salivary Gland-Type Tumors With Myoepithelial Differentiation Arising in Pulmonary Hamartoma: Report of 2 Cases of a Hitherto Unrecognized Association. Pelosi G, Rodriguez J, Viale G, Rosai J. *Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy daggerOncologic Pathology Consultation Center, Italian Diagnostic Center, Milan, Italy.	Am J Surg Pathol. 2006 Mar;30(3):375-387. Abstract quote   Reported is a hitherto unrecognized association of pulmonary hamartomas with salivary gland-type tumors showing myoepithelial differentiation, namely, a case of myoepithelioma arising in a otherwise classic hamartoma with cartilage predominance, and a case of malignant mixed tumor arising in a predominantly fibrous hamartoma resembling mullerian adenofibroma. The tumors occurred in middle-aged female patients of 35 and 44 years, respectively, and presented as 7 cm (treated with lobectomy) and 13 cm (treated with pneumonectomy) masses of the right upper lobe showing a short clinical history of cough, dyspnea, and wheezing. Both lesions did not present regional lymph node metastases after mediastinal lymphadenectomy. The myoepithelioma patient was well with no signs of recurrent disease at 6-month clinical control, but she was then lost to follow-up; the malignant mixed tumor patient is alive and well after 6 months since operation. Both tumors presented with morphologic and immunohistochemical features of myoepithelial cells, and we interpret them as being derived from a myoepithelial-like stromal cell population found within the hamartomatous areas, which is also consistently detected in classic pulmonary hamartoma. The lack of individual cell necrosis, mitotic activity, cell atypia, and pulmonary parenchyma infiltration supported a diagnosis of benign or unproven malignant potential tumor for the myoepithelioma, whereas the reverse held true for the other tumor in which the diagnosis of malignant mixed tumor of the lung was rendered. Their main importance of recognizing this association lies in separating these tumors histologically from other monophasic or biphasic tumors, either primary or secondary, such as pulmonary sarcomatoid carcinomas or true sarcomas, and metastatic salivary gland tumors, spindle cell carcinomas, melanomas, and soft tissue and visceral sarcomas.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
IMMUNO-FLUORESCENCE
Direct and indirect immunofluorescence as a diagnostic adjunct in the interpretation of nonneoplastic medical lung disease. Magro CM, Morrison C, Pope-Harman A, Rothrauff SK, Ross P Jr. Department of Pathology, Ohio State University Medical Center, Columbus, USA.	Am J Clin Pathol 2003 Feb;119(2):279-89 Abstract quote Fresh open lung biopsy material from 57 patients was incubated with fluoresceinated complement and immunoglobulin antisera. An indirect immunofluorescent assay using neonatal lung as substrate was conducted as well. Direct immunofluorescent patterns could be categorized into interalveolar septal capillary deposition, large vessel wall localization, alveolar basement membrane localization, or a pauci-immune immunofluorescence pattern. With respect to the septal capillary pattern, endothelial cell decoration was seen with scleroderma, mixed connective tissue disease, anti-Ro-associated lupus erythematosus, dermatomyositis, humoral allograft rejection, and patients with isolated pulmonary fibrosis in whom autoantibodies were established, including antiphospholipid antibodies. A similar pattern of endothelial cell staining was seen in these cases via the indirect assay. Granular mural septal capillary deposition was seen in the aforesaid settings along with rheumatoid factor-positive rheumatoid arthritis, type II cryofibrinogenemia, and mixed cryoglobulinemia and, in some cases, light microscopically corresponded to a neutrophilic capillaritis. Isolated vascular IgA corresponded with rheumatoid arthritis corresponding to IgA-specific antiendothelial cell antibodies, celiac disease-associated pulmonary hemorrhage, Schonlein-Henoch purpura and with IgA antiphospholipid antibodies. Alveolar wall deposition was seen with anti-glomerular basement membrane disease.

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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
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Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Consolidation-Solidification of the lung secondary to pus and exudate.  Often present in bacterial pneumonias.

Curschmann's Spirals-Collections of shed epithelium arranged in whorls mixed with mucous. Often found in asthma. 

Diffuse Alveolar Damage-This is the histologic equivalent of Adult Respiratory Distress Syndrome or Shock Lung. 

Hyaline Membranes-These are waxy fibrin rich collections which line the alveolar spaces.  It is a hallmark of diffuse alveolar damage.

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