Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 03-33330A cytokeratin Bovine Cytokeratin-normal 03-33330B cytokeratin Bovine Cytokeratin-normal lung 07-107482-A1 Porcine Swine influenza Swine influenza--with nice IHC. 38514-98 Wild boar Metastrongylus 98-38514-5 Feedlot steer, bronchiolitis obliterans, as a sequel to viral bronchiolar necrosis, with arteriolar hypertrophy and 97-3591 Bovine Bronchiolitis fibrosa obliterans failure 98-887-20A 20hrs pi 20 hours after Mannheimia challenge 98-887-20B 20hrs pi 20 hours after Mannheimia challenge 98-887-3A 3hrs pi 3 hours after Mannheimia challenge 98-887 Lambs with low antibody titres, challenged by aerosol with PI3V then 6 x 10^8 cfu of M. haemolytica. 98-887-3B 3hrs pi 3 hours after Mannheimia challenge 98-887-8A 8hrs pi 8 hours after Mannheimia challenge 98-887-8B 8hrs pi 8 hours after Mannheimia challenge ACVP-81 Equine Silicosis Slide from an old ACVP meeting. Gross postmortem examination reveals multifocal, well-demarcated, pale, bulging, solid regions within all lung lobes (from <1 to 4cm dia). Contained airways exude frothy fluid although only small amounts of such fluid is noted in the mainstem bronchi or trachea. Histopathological examination of affected lung reveals multifocal, unencapsulated regions where the alveolar architecture is obscured by complex acinar & papillary arrangements of well regimented columnar cells on thin fibrovascular septi. These cells are densely packed, have pale eosinophilic to clear cytoplasm & basally orientated vesicular nuclei. Mitotic figures are inconspicuous. Infiltrates of neutrophils & macrophages are noted within contained & adjacent airspaces. No significant D08-26 Ovine Jaagsiekte N76/08 abnormalities noted within mediastinal lymph node sample. Incidental finding in the lung of an adult horse. The lung lesion is well-demarcated and delineated by a fibrous capsule, with an area of mature fibrosis in the adjacent lung tissue and pleura. The wall of the cyst is formed by a laminated layer of basophilic mucinous material, and an inner layer of cuboidal cells. The innermost aspect contains innumerable multifocal 100-um aggregates of mineralized debris, and rare similarly sized structures N124108A Equine Echinococcus N124108A with viable cells and several refractile hooks (indicating that they are protoscolices of Echinococcus granulosus). Dog was attacked and shaken by another dog. The lung is markedly congested and edematous, and close inspection reveals many thin hyaline membranes lining the surface of the alveoli. Alveolar hemorrhage is present but mild. This is an example of acute respiratory distress syndrome, probably as a result of trauma, PB-Ca8 Canine Diffuse alveolar damage (ARDS), 2ry to trauma 04-60164-A asphyxiation, or both. PB-Ca9 Bovine Endotoxemic lung injury 00-16766-2 Endotoxemic lung injury. Cow, acute mastitis, dyspnea 12 hours after calving. Cow. Massive from a in the uterine vein. Cow at Elora was examined and treated by 4th year vet students, who then went elsewhere in the barn to treat another cow. When they returned, the cow was dead, and necropsy revealed metritis with a thrombus in the uterine vein, and massive PB-Cb4 Bovine Pulmonary embolus 67805-2 pulmonary embolism. Dog. Interstitial fibrosis secondary to chronic heart failure. 10 year old Calvalier King Charles Spaniel, with a chronic history of mitral valve disease. Gross: left AV valvular endocardiosis, left atrial dilatation, left PB-Cb5 Dog Interstitial fibrosis 2ry to chronic heart failure. 96-514-5 ventricular eccentric hypertrophy, one ruptured chorda tendinae, and pulmonary edema and congestion. PB-Cc100 Canine Blastomycosis Experimental with Nipah virus. Attenuation of tracheal surface epithelium, with lymphocytic tracheitis and moderate numbers of eosinophils, lymphocytes cluster within tracheal epithelium. Patchy suppurative exudate within the lumen. One area has single cell necrosis of epithelial cells, and possible PB-Cc103 Pig Nipah virus: tracheal epithelial necrosis 04-303-40B inclusions (or uptake of apoptotic cells?). PB-Cc104 Calf Embolic pneumonia 2ry to endocarditis 65151-2 Embolic pneumonia 2ry to endocarditis PB-Cc105 Dog Cryptococcosis 02-32154-13 PB-Cc94a PB-Cc94b PB-Cc94c PB-Cc96 Cat? Idiopathic pulmonary fibrosis?

Page 1 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details PB-Cc98 Horse? Heaves? PB-Cd11a Feline Pulmonary adenocarcinoma nasal adenocarcinoma; has had unilateral nasal disease for >1 year and a diagnosis of lymphoplasmacytic rhinitis PB-Cd12 Canine Nasal adenocarcinoma YB133947 last year PB-Cf13 Feline Idiopathic pulmonary fibrosis 05-15413 chronic interstitial pneumonia / idiopathic pulmonary fibrosis with pulmonary carcinoma Chronic proliferative interstitial pneumonia/idiopathic pulmonary fibrosis. 8 year old cat. Born in South Africa. Hiding, stopped eating. Vague clinical signs. Also has severe hepatic lipidosis. Histo: Irregular distribution of chronic interstitial lung disease with type II pneumocyte proliferation, remarkable hyperplasia/metaplasia of smooth muscle, and mild fibrosis. Fragments of blue-gray material are present in PB-Cf14 Feline Idiopathic pulmonary fibrosis, smooth muscle hyperplasia D05-06 alveoli (rule out inhalation of bentonite-cat litter dusts as pneumoconiosis?). YB 132809. PB-Cf15 Bovine Normal bovine lung 97-2054 PB-Cf16 Canine Normal canine lung D09-04 The lung is immature with an excess of connective tissue in the alveolar septa. Many of the alveoli are lined by hyaline membranes, and cuboidal epithelium lining the hyaline membranes is occasionally still present (probably has not yet differentiated to type 1 pneumocytes, rather than a reversion). Keratin squames are present in the PB-RESP-1 Puppy, 1 d old Puppy. Neonatal ARDS / hyaline membrane disease 02-D14 alveoli. The the fine black pigment within some cells is acid hematin (artifactual). Renal disease last year, renal transplant, great postop. One month hx lethargy, 2 wk hx anorexia/inappetance. Developed dyspnea 5d ago, Chest rads - patchy diffuse infiltrates. Cyclosporin level very elevated (1500!). PM: lung is diffusely firm and has multifocal coalescing white consolidated depressed areas (0.5 - 3 cm), mostly present in the cranioventral lobes and rarely in the caudodorsal parts. On cut section, lung has a dry congested surface that alternates with the white consolidated areas. Also multifocal hepatic necrosis. Histo: Multifocal random lesions of inflammation and necrosis, in which alveoli are lined by cuboidal type 2 pneumocytes and filled with necrotic cellular debris, basophilic chromatin debris, neutrophils, macrophages. The epithelial cells contain large numbers of protozoal cysts, which are up to 25 microns diameter and contain numerous zoites. PB-RESP-2 Cat Cat. Pulmonary toxoplasmosis 02-31610-2 Multifocal necrotizing and proliferative interstitial pneumonia with protozoal cysts. 13-yr-old dog, incidental finding.The pulmonary tumor is poorly demarcated, non-encapsulated, and occupies most of the section in those affected. In many areas, the arrangement of neoplastic cells mimics that of normal alveoli -- the tumor forms multiple epithelial-lined air spaces separated by fibrous trabeculae. The neoplastic cells are cuboidal, with indistinct borders, scant eosinophilic cytoplasm, round nuclei with finely clumped chromatin, 2-fold anisokaryosis, and rare mitotic figures. A prominent feature of the tumor is the presence of 5- 100 micron diameter concretions of brightly eosinophilic material (surfactant-like proteins?) within the air spaces. Occasionally, neoplastic epithelial cells tightly encircle this material, suggesting that it is being secreted Dog. Pulmonary adenocarcinoma; some features of by the tumor cells. In addition, there are numerous macrophages, occasional neutrophils, and cellular debris in PB-RESP-3 Dog bronchioloalveolar carcinoma D03-92-1 the air spaces. The areas in which alveoli are Adult dog, unilateral bloody nasal discharge. The tissue consists entirely of plaques of fungal hyphae which PB-RESP-5 Dog Dog. Nasal aspergillosis 93-2024 show features characteristic of Aspergillus: parallel walls, 4-micron-diameter, dichotomous branching, Bronchioles are markedly dilated and there is corresponding atelectasis of the alveoli. The bronchioles often contain neutrophils, with occasional erosion of the epithelium. In some bronchioles, the brush border is unexpectedly dense and slightly basophilic. A Warthin Starry silver stain reveals that this is the result of many PB-RESP-6 Rat CAR bacillus with bronchiectasis. D05-109. YB146764 bacilli adherent to the cilia. Mycoplasma pneumoniae is a differential diagnosis for bronchiectasis in rats. Bronchioles are markedly dilated and there is corresponding atelectasis of the alveoli. The bronchioles often contain neutrophils, with occasional erosion of the epithelium. In some bronchioles, the brush border is unexpectedly dense and slightly basophilic. A Warthin Starry silver stain reveals that this is the result of many PB-RESP-7 Rat CAR bacillus --Warthin Starry stain of above. D05-109. YB146764 bacilli adherent to the cilia. Mycoplasma pneumoniae is a differential diagnosis for bronchiectasis in rats. Several of the airways are tremendously dilated and occupy the majority of the section. These are filled with an exudate of neutrophils, the epithelial lining has undergone squamous metaplasia or is eroded, and there is granulation tissue leading to fibrosis of the airway wall. The surrounding lung tissue is atelectatic due to airway PB-RESP-8 Bovine Bovine. Bronchiectasis Cc55 obstruction. Bronchiectasis. PB-RESP-10 Calf Calf. Atelectasis due to bronchiolitis 435-67 RCX PB-RESP-11 Pig Pulmonary edema, pigs died in power failure 98-38369-A1 Protein-rich alveolar edema, presumably due to endothelial retraction from heat stress

Page 2 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Alveolar septa are diffusely thickened by mononuclear cells -- probably both macrophages and lymphocytes. Lymphocytes encircle bronchioles and airways, but bronchiolar necrosis is never present in this disease. Suppurative bronchopneumonia is also present in one section. Lymphocytic interstitial pneumonia due to PRRS. Numerous Pneumocystis fill alveoli in some areas (subpleural in the triangular section of lung, adjacent PB-RESP-12a Pig Pig. PRRS and Pneumocystis 99-1309-2 to the fatty liver). Alveolar septa are diffusely thickened by mononuclear cells -- probably both macrophages and lymphocytes. Lymphocytes encircle bronchioles and airways, but bronchiolar necrosis is never present in this disease. Suppurative bronchopneumonia is also present in one section. Lymphocytic interstitial pneumonia due to PRRS. Numerous Pneumocystis fill alveoli in some areas (subpleural in the triangular section of lung, adjacent PB-RESP-12b Pig Pig. PRRS and Pneumocystis 99-1309-2 to the fatty liver). Alveolar septa are diffusely thickened by mononuclear cells -- probably both macrophages and lymphocytes. Lymphocytes encircle bronchioles and airways, but bronchiolar necrosis is never present in this disease. Suppurative bronchopneumonia is also present in one section. Lymphocytic interstitial pneumonia due to PRRS. Numerous Pneumocystis fill alveoli in some areas (subpleural in the triangular section of lung, adjacent PB-RESP-12c Pig Pig. PRRS and Pneumocystis 99-1309-2 to the fatty liver). 4 month old Standardbred foal. Noted by owner to be a bit dull for the past couple of weeks, and got much worse 3 days ago. Treated with antibiotics for 2 days then euthanized. The veterinarian describes multiple abscesses in the cranial lung. The section is entirely consolidated, and both bronchioles and alveoli are filled with neutrophils. Many of these alveoli are entirely lined by cuboidal epithelium, and occasional multinucleate syncytia are present in the alveoli. The bronchiolar epithelium is irregularly hyperplastic/dysplastic. In addition, there are liquefying areas containing numerous neutrophils and fewer macrophages, and macrophages in these areas are occasionally greatly enlarged and contain myriad basophilic bacteria in their cytoplasm (highlighted in blue with the Gram stain -- slide #14). Diagnoses: pyogranulomatous bronchopneumonia (Rhodococcus); PB-RESP-13 Foal Foal. Rhodococcus equi 99-01247 chronic bronchointerstitial pneumonia with syncytia (bronchointerstitial pneumonia of foals). PB-RESP-14 Equine Foal. Rhodococcus equi- B&B stain 99-01247 See above. The lesion is patchy in its distribution. In the affected areas, many of the alveoli are completely or partially filled with homogeneous, dark-pink material. Type 2 pneumocytes proliferation is prominent in many of the alveoli leading to a cuboidal lining. There are numerous leukocytes and fewer macrophages in the interstitium. The PB-RESP-15 Goat Goat. Pneumonia due to caprine arthritis encephalitis virus 99-01515-2 abnormal areas of lung are edematous. The bronchioles are normal. The lung is atelectatic. Many of the small bronchioles are lined by attenuated epithelium that contains many multinucleate syncytial cells, and necrotic cellular debris and neutrophils fill the lumen. The alveoli are PB-RESP-16 Calf Bovine respiratory syncytial virus 99-2240-1 atelectatic, contain edema fluid and neutrophils, and occasional syncytia are present. Swine influenza. The lesion in one section is dominated by suppurative bronchopneumonia. Suppurative proper pneumonia is also present in the other section. However, in addition, a minority of the bronchioles are lined by markedly attenuated epithelium and contain low numbers of neutrophils in their walls. Note that the alveoli are normal apart from the proper pneumonia and atelectasis -- influences typically causes necrosis only in PB-RESP-17 Pig Swine influenza. Bronchiolar necrosis 99-303-A1 the bronchioles. Airways and vessels are surrounded by many lymphocytes, and there is variable diffuse thickening of alveolar septa by mononuclear cells. In slide #21, macrophages and lymphocytes filled the alveoli (air spaces) as well. Bronchiolar necrosis may be present in this disease, but is not appreciated in this case. Thus, the lesion in this case would be indistinguishable from PRRS. The kidney contains patchy cortical infiltrates of lymphocytes. In the ileum, the Peyer's patches are partially depleted of lymphocytes and infiltrated by macrophages, and these macrophages occasionally contain multiple intracytoplasmic basophilic inclusion bodies. Similarly, lymphoid PB-RESP-21ab Pig Porcine circovirus 99-38170-C depletion and macrophages filtration are prominent in the lymph node, and inclusions are present.

Page 3 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Airways and blood vessels are surrounded by many lymphocytes, and there is variable diffuse thickening of alveolar septa by mononuclear cells. In slide #21, macrophages and lymphocytes filled the alveoli (air spaces) as well. Bronchiolar necrosis may be present in this disease, but is not appreciated in this case. Thus, the lesion in this case would be indistinguishable from PRRS. The kidney contains patchy cortical infiltrates of lymphocytes. In the ileum, the Peyer's patches are partially depleted of lymphocytes and infiltrated by macrophages, and these macrophages occasionally contain multiple intracytoplasmic basophilic inclusion bodies. Similarly, lymphoid PB-RESP-21c Pig Porcine circovirus 99-38170-C depletion and macrophages filtration are prominent in the lymph node, and inclusions are present. PB-RESP-22 Bovine Bovine. Diffuse alveolar damage without bronchiolar necrosis 14848 The lung contains a nodular lesion composed of coalescing, caseous granulomas. These each contain a central area of caseous necrosis, with numerous yeast bodies. The yeast are 10-micron-diameter, with a thick refractile cell wall, and occasional broad-based budding. Many of the yeast are apparently empty (dead), while others (the live ones) have a basophilic granular nucleus. These foci of necrosis are surrounded by macrophages that have abundant cytoplasm, and are occasionally elongate or epithelioid. Numerous lymphocytes infiltrate the adjacent PB-RESP-23 Dog Dog. Blastomyces dermatitidis 99-71545-1 tissue. Several sections are congested but otherwise normal. One section (long rectangle) came from one of several focal lesions in the lung of this cow with toxic mastitis. This section contains extensive serofibrinous exudate (protein-rich edema with lacy strands of fibrin) with increased numbers of macrophages and a few neutrophils hyaline membranes are rare. Might this be an infarct secondary to ? More typical lesions of endotoxemia are diffuse pulmonary edema, diffuse serofibrinous alveolar exudate, and/or increased numbers of PB-RESP-25 Cow with acute mastitis Cow. Endotoxemic lung injury secondary to acute mastitis 99-71621-4 mononuclear cells through the alveolar septa. Mycoplasma hyopneumoniae. Thick cuffs of lymphocytes bronchioles and extend into the lamina propria. The bronchioles occasionally contain neutrophils in their lumen, and bronchiolar epithelial hyperplasia may be present. The alveoli are edematous and contain increased numbers of macrophages and lymphocytes -- a PB-RESP-26 Pig Pig. Mycoplasma hyopneumoniae 10160A frequent finding in this disease. Piglet, 35 days old, incidental finding, PM: nasal passages filled with discharge. Diffuse lymphocytic rhinitis. The additional lesions are not numerous, but are found in several areas including the nubbin protruding from the turbinate near its junction with the septum. In these areas, some of the epithelial cells lining the mucosal glands are enlarged up to 30-micron-diameter, with pale vacuolated cytoplasm and a large (15 micron) blue- PB-RESP-27 Pig Pig. Cytomegalovirus- inclusion body rhinitis 00-15445-4 purple smudgy nucleus. These represent cytomegalic cells with intranuclear inclusions. Dog, 6 yrs of heart failure, 2 months renal failure, hypothyroid, recent lethargy anorexia, dysphagia. PM: coalescing pattern of lesions in the ventral lung, affecting 20% of the lung. Lesions appear to encircle small airways, are firm pale, & are reticular at the edge of the lesion. Histo: The lesion is patchy in its distribution. In the affected areas, many of the alveoli are filled with irregularly shaped, homogeneous, grey-khaki masses of material. These are partially encircled by macrophages and multinucleate giant cells, and a similar population of cells is present in the bronchioles. The alveolar septa are thickened by fibrous tissue and perhaps smooth PB-RESP-28 Dog Dog. Alveolar proteinosis 00-30559-1 muscle. Patchy aggregates of lymphocytes are present around blood vessels. Horse with chronic respiratory disease, died in status asthmaticus-like condition. Lesions targeted the bronchioles and spare the alveoli. Many bronchioles are filled with mucous and with neutrophils. There is mucous metaplasia of bronchiolar epithelium (goblet cells where there are normally none) increased numbers of lymphocytes and plasma cells in the lamina propria and adventitia, and increased prominence of the bronchiolar smooth muscle (reflecting chronic bronchoconstriction). In addition, some bronchioles have hyperplasia or squamous metaplasia of the epithelium, and fibrosis of the airway wall (which is the "airway remodeling" that is a hot topic in human asthma research). The alveoli are often overdistended (due to partial airway obstruction), PB-RESP-29 Horse Horse. Heaves 01-38976-3 or occasionally atelectatic (due to complete airway obstruction). Bovine respiratory syncytial virus. This case is probably more subacute than that in #16. There is much more prominent attenuation of bronchiolar epithelium, but although syncytia are present they are infrequent. The alveoli contain many neutrophils and macrophages, with extensive proliferation of type 2 pneumocytes and PB-RESP-30 Calf Calf. BRSV. Bronchointerstitial pneumonia without syncytia 01-50585-2 formation of alveolar syncytia is present.

Page 4 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 13 year old cat, 4 year history of asthma controlled with cyprohepatidine, recent (2 day) history of viral upper respir infection treated with cephalexin, died acutely. Lesions target the airways and spare the alveoli. Many bronchioles have large numbers of lymphocytes in their walls which form follicular structures. Hyperplasia/hypertrophy of the bronchial mucosal glands is prominent, and there is equivocal increase in prominence of the smooth muscle. Mucus and neutrophils fill the bronchiolar lumen. The alveoli are overdistended, but otherwise normal (apart from an increased amount of smooth muscle mainly in the alveolar ducts). This lesion is suppurative and eosinophils are not present. Nevertheless, it is thought that this lesion represents chronic bronchitis/bronchiolitis due to hypersensitivity, rather than bacterial infection. IHC= 06- PB-RESP-31 Cat Cat. Feline asthma D03-94 50797. These is an "essentially normal" dog lung from a research study, but illustrate several incidental findings. There are occasional aggregates of lymphocytes adjacent to airways or blood vessels. A wedge-shaped area of subpleural fibrosis with accumulation of lymphocytes and macrophages is present, and the adjacent mesothelial cells are hypertrophied (perhaps a chronic infarct? A few sub-pleural clusters of alveoli contain foamy macrophages, termed alveolar histiocytosis. A 200-micron-diameter focus of osseous metaplasia is present. Occasional terminal bronchioles contain proliferation of cuboidal epithelial cells that extend along the adjacent PB-RESP-32 Dog Dog. Alveolar histiocytosis, bronchioloalveolar hyperplasia 02-55389-K alveoli -- bronchioloalveolar hyperplasia. 12-year-old FS Shiba Inu dog. Honking cough for a week, then increased respiratory effort (day 0), worsened over 2 days. Pericardial effusion (day 7). Normal serum albumin, no proteinuria. Hemorrhagic (day 9) with epistaxis, cutaneous , from injection sites. Alveolar radiographic pattern, pleural effusion. Ultrasound: enlarged right atrium & ventricle, enlarged pulmonary artery with pulmonary arterial hypertension, reduced filling of left ventricle. Markedly prolonged PT & PTT, no detectable plasma fibrinogen, elevated fibrin degradation products. Necropsy: -diffusely edematous, rubbery, congested; no thrombi, parasites, or anomalies; liver mildly enlarged; cutaneous petechiae, black flecks in gastric mucus. Histo: Small pulmonary arteries are more prominent than normal with increased cellularity of tunica into a from endothelial proliferation (FVIIIra+). Some of these blood vessels appear as a plexus of anastomosing channels, termed plexiform arteriopathy as is seen in human primary pulmonary hypertension. Increased numbers of alveolar macrophages throughout the lung, with patchy edema; alveolar septa mildly hypercellular. Diagnosis: pulmonary arterial PB-RESP-34 Dog. Pulmonary hypertension with plexiform arteriopathy of small arteries. 05-32203 intimal proliferation with plexiform arteriopathy, the result of idiopathic pulmonary hypertension The lung contains multifocal plaques on the pleural surface, which consist of fibrin, neutrophils, and macrophages. Lymphocytes and plasma cells are present in the underlying pleural tissue. The pleura adjacent to these lesions is lined by plump mesothelial cells. The lung is atelectatic. A similar inflammatory lesion is present in a second section of tissue (pericardium?), and both on the capsular surface and within portal tracts in the liver. The lymph nodes contain multifocal inflammatory lesions, which have neutrophils, macrophages, and fibrin in their centers, surrounded by lymphocytes and plasma cells. Histologic lesions are not present in the PB-RESP-35 Dog Feline infectious peritonitis--pleuritis with atelectasis, lymphadenitis D05-147. YB153172 sections of kidney, or spleen. Dx: pyogranulomatous pleuritis, peritonitis, hepatitis, and lymphadenitis; typical of Foal EHV abortion: intranuclear inclusion bodies in bronchiolar epithelium, keratin squames numerous in PB-RESP-36 Equine Equine herpesvirus abortion-lung, spleen 06-14583-7 alveoli and bronchioles, spleen-lymphoid necrosis with inclusion bodies. Incidental finding at the tracheal bifurcation of a dog. A nodular mucosal lesion protrudes into the lumen, and is formed by many cross-sections of adults nematodes with a lymphoplasmacytic inflammatory reaction. Internal organs of the worms are in a pseudocoelom, including an intestine formed by cuboidal syncytial cells with an indistinct brush border, and a uterus containing many eggs some of which are embryonated. The PB-RESP-37 Dog Dog. Oslerus osleri 3477-67 musculature is very thin, and spines adorn the cuticle.

Page 5 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Jack Russell terrier, appx 4-yr-old, 2 wk. hx. of coughing, reduced appetite, increased RR. Tx. with clindamycin, enrofloxacin, solu-delta (x2 days). The developed facial swelling, acutely dyspnea-anaphylactic rxn to antibiotics? X rays marked diffuse severe patchy interstitial - alveolar pattern. Frank hemorrhage within lung, drained frank blood from intratracheal tube. Euthanized. Gross: subcutaneous hemorrhages in forelegs and pinna; Blood oozed from nares; lungs were mottled bright and dark red, failed to collapse, and oozed large amounts of blood when cut. Histo: (a) extensive hemorrhage, (b) suppurative vasculitis affecting arteries as well as the small capillaries in alveolar septa; (c) neutrophil infiltrates in the lung, (d) sheets of macrophages (which Pulmonary hemorrhage due to suppurative vasculitis, with were CD18+). Also had vasculitis in the ear skin. This represents pulmonary hemorrhage due to vasculitis; the PB-RESP-39 Dog suppurative and histiocytic pneumonia 05-55670-2 cause of the vasculitis is obscure, some feature are reminiscent of Wegener's granulomatosis in humans. Nipah virus infection. Degenerative changes in olfactory epithelium, Nipah virus infection. Lymphocytic rhinitis, degenerative changes in olfactory epithelium (nuclear swelling of PB-RESP-40 Pig lymphocytic rhinitis. Nasal anatomy. D04-339-32J olfactory neurons, blebbing at surface). Note the histologic appearances of respiratory & olfactory epithelium. Put on erythromycin and rifampin June 6/03. On Ventipulmin last 3-4 days. Treated with Anafen as needed for high temps. Had high temp and rapid respiration last 3 days - improved June 21 with temp and RR. Temp at midnight 38.8 C. Died quietly - June 22/03. Severe bronchointerstitial pneumonia with bronchiolitis, PB-RESP-41 Equine Bronchointerstitial pneumonia of foals, many syncytia 03-33431-2 alveolitis and moderate numbers of syncytial cells in air passages and alveoli. PB-RESP-42 Dog Dog. Canine distemper with syncytia 9296 5-yr-old ewe, 2 months post partum, normal until day of death, standing and staring (brain was not examined- visna??). Histo: Most small and medium sized blood vessels and fewer bronchioles are surrounded by wide lymphocytic cuffs. Smooth muscle hyperplasia expands the walls of many terminal bronchioles, and alveolar walls are thickened by fibrosis. Most alveoli contain small clusters of macrophages and many are lined by PB-RESP-44 Sheep Maedi. 02-30892 hyperplastic type II pneumocytes. Mannheimia. Calf originated from Western Canada; was purchased Oct. 24/01. Vaccinated less than 48 hours after purchase with Resvac 4, injected with LA Liquamycin 200, no antibiotics in feed/water. Calf was first treated for illness Dec 17/01 - respiratory signs/coughing, depression. Calf died Dec. 19/01, overnight. Approximately 60 percent of the cranioventral region of the lungs is dark red and firm with a small amount of fibrin on the pleural surface. Affected areas of the lungs have irregular, white and well- demarcated areas of necrosis. In the right middle lobe of the lungs there is a red-black area of about 6 x 8 cm representating an area of hemorrhage and necrosis. The entire trachea contains a large amount of white-yellow fibrin adherent to mucosal surface (calf had concurrent IBR). Only E.coli was isolated from lung. Histo: Large amounts of fibrin, many neutrophils and macrophages fill the alveolar spaces. Many of the infiltrated neutrophils and macrophages are necrotic and have streaming nuclei. There is necrosis of the alveoli in the areas with marked infiltration of neutrophils. In some areas there are large numbers of red cells in the alveolar spaces. The severity of the lesions have lobular pattern. Many bronchioles in the affected areas contain intraluminal accumulation of degenerative neutrophils, fibrin and cellular debris. There are several early M bovis like lesions, which consist of focal aggregates of eosinophilic necrotic cells. Marked edema, fibrin, hemorrhages and infiltration of many neutrophils markedly thicken the interlobular septa and pleura. Pleura has also mild fibroplasia with PB-RESP-45 Bovine Mannheimia-fibrinosuppurative bronchopneumonia 01-51794-2 neovascularization and abundant fibrin on the pleural surface. Thrombosed lymphatic and blood vessels are in 3 year old goat that died of lymphoma. A subpleural nodule contains large numbers of nematodes, including eggs, curved and coiled larva (some with dorsal spines?); and low numbers of adults that have a very thin polymyarian-coelomyarian musculature, and an intestine composed of few multinucleate cells with an indistinct brush border. The alveoli contain numerous macrophages and lymphocytes, and there is extensive smooth muscle hyperplasia (which can form a residual lesion within the worms are eventually cleared.). Also lymphoma PB-RESP-46 Goat Muellerius capillaris 03-38587-1 in the section of kidney, which was the cause of death. B6C3F1 mouse. Multifocal bronchioloalveolar carcinomas, and PB-RESP-47 Mouse acidophilic macrophage pneumonia. CMHD 150-s338. E04-24a B6C3F1 mouse. Common background findings in this strain of mouse.

Page 6 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Mycoplasma bovis. Charolais-X heifer - Vaccinated with Pyramid 4 after arrival from Western Canada, 6 weeks previously. First treated for illness 10 days after. Animals presented with diarrhea progressing to lameness; respiratory signs. Animal was recumbent during examination. Treated with several label doses of Micotil at 3- day intervals. Last treatment Nov 8. Euthanized Nov 12/01. There are multifocal intense eosinophilic areas of caseous necrosis bordered by infiltration of many degenerated and non-degenerated neutrophils. These foci are frequently coalescing and are bordered at periphery by thick walls of infiltration with many lymphocytes, plasma cells and macrophages admixed with abundant granulation tissue, fibrin and neovascularization with a gradual transition to mature fibrous tissue in some areas. Many bronchioles are filled with variable numbers of necrotic inflammatory cells predominantly neutrophils mixed with sloughed/necrotic epithelial cells and cellular debris and there is peribronchiolar cuffing with large numbers of lymphocytes and plasma cells. The affected bronchiolar epithelium is eroded and/or ulcerated. The pulmonary parenchyma between these foci consists of partially collapsed alveoli filled with abundant proteinaceous material, fibrin, and mild to moderate numbers of macrophages with a few neutrophils and sometimes red cells. In other areas there is marked distention and fusion of multiple alveolar spaces. In some sections, many small and mid-size arteries have fibrinoid degeneration, necrotic smooth muscle cells of the tunica media and infiltration of a few mononuclear cells predominantly lymphocytes (concurrent acute BVDV infection). PB-RESP-48 Bovine Mycoplasma bovis pneumonia 01-47262-1 4 Week old kitten. Anorexia and poor doer. Kitten had been one of litter of 4, one died at 2 week, another had severe conjunctivitis but is doing well. Zeus had stopped eating June 20 and was admitted, tube feeding supportive care caused cat to rally for a short time. Blood samples for Glucose, PCV, BUN, total solids, Felv/FIV all negative or normal. GROSS: This kitten is thin and without body fat. Lungs are mottled and firm to nodular on palpation. Heart appears normal. Stomach is empty, colon contains semi-formed feces. HISTO: Marked mineralization of stroma of bronchi, bronchioles, terminal airways and alveolar septae with mild patchy fibrosis and increased mononuclear cellularity. Some areas are totally atelectatic; others have alveolar emphysema. KIDNEY - Few mineralized concretions in tubules; no other recognizable changes. Normal heart, intestine, liver. Histological Diagnosis: Massive pulmonary mineralization. Comment: Thyroid-parathyroid misplaced; tissues retrimmed and could not identify any thyroid tissue. At any rate, the 'pure' presence of mineralization in lung without any renal lesion indicates that there is not a primary or secondary parathyroid problem. Assumedly this represents a congenital defect of connective tissue of lung; I have been unable to find any description of this in Sphynx cats but will seek further opinions also. [is not renal hyperparathyroidism since PB-RESP-49 Cat Pulmonary mineralization (not uremic) 05-33286-1 kidney is normal; also consider metabolic alkalosis, toxicity, ???) 9-mos-old Old English sheepdog. Surgery for intussusception 1 week ago. Noticed abnormal lungs on radiographs just before the surgery. Developed respiratory distress. The entire right middle lung lobe was excised at surgery. It was markedly distended and pink, and did not sink in formalin. The bronchioles were prominent and a small air-filled region of the parenchyma was noted adjacent to the airway. Histo: marked enlargement and hyperinflation of alveoli, with some loss and/or displacement of alveolar walls. Those remaining are often thickened. There are multifocal regions of parenchymal necrosis with hemorrhage along the edges of the lobe, with hemosiderin-laden macrophages, fibrous connective tissue, type II pneumocyte hyperplasia and fibrin. Diagnosis: Lobar emphysema with multifocal hemorrhagic infarcts. Comments: The infarctions are likely secondary to the emphysema, resulting from over-inflation and rupture of alveolar walls. Most cases of congenital lobar emphysema are reported to occur in the right middle lung lobe. Cartilage PB-RESP-51 Dog Infarction due to congenital lobar emphysema (vs. lung lobe torsion?) 05-13764-a abnormalities are described in other cases but were not found in this case.

Page 7 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Equine multinodular pulmonary fibrosis. Mare, age unknown, respiratory disease of at least 4 months duration. PM: multifocal coalescing 2-20 cm diameter white, raised, firm to hard masses that are firm and homogeneous on cut surface, affecting about 85% of the dorsocaudal lung fields; cranioventral lobes have scattered nodules with smooth borders and sharp demarcation between normal and abnormal tissue; one bronchial lymph node is enlarged and firm. The multifocal white nodules observed grossly correspond with areas of dense mature interstitial fibrosis with marked infiltration by mononuclear cells. Alveoli are separated from one another and from blood vessels by dense bands of fibrosis and are lined by hyperplastic type 2 pneumocytes. Alveolar lumens are filled with neutrophils and exfoliated epithelial cells and there are large round amphophilic inclusions within the nuclei of exfoliated epithelial cells, consistent with adenoviral inclusions. Bronchiolar epithelium is hyperplastic, with almost no goblet cells, and there are focal areas of bronchiolar necrosis. Bronchiolar lumens are also filled with neutrophils and exfoliated cells. Viral inclusions are only seen in exfoliated epithelial cells. There is a dense band of hemorrhage at the margin between affected and unaffected lung. In the grossly unaffected areas there is extensive hemorrhage with neutrophils within alveolar septa and alveolar sacs, acute bronchiolar necrosis and also multifocal areas of acute necrosis with fibrin and degenerative neutrophils. There PB-RESP-52 Horse Equine multinodular pulmonary fibrosis 03-25551-2 is fibrosis surrounding blood vessels and some larger airways. Referring veterinarian indicates he has seen the dog for at least 4 years and has never administered barium to it. Incidental finding at necropsy?? Multiple deposits of crystals, usually centred on alveoli. In areas of crystal deposition, there is loss of alveolar architecture, filling of space by innumerable, extracellular & intracellular, angular, 1-15 um clear birefringent crystals; many macrophages (and type II pneumocytes??), & mild fibrosis. X- ray diffraction crystallography--Barium sulfate. See data: Barium crystal pneumoconiosis- Xray diffraction PB-RESP-53 Dog Pneumoconiosis--Granulomatous pneumonia with barium crystals D06-57 crystallography D06-57.doc PB-RESP-54 Bovine Chronic suppurative bronchitis with mucous metaplasia 39144 PB-RESP-55 Dog Heart failure with marked hemosiderosis 39065 Lung from a cat, and material that was attached to the costal/parietal pleura (ignore the thymus). The cat presented with an acute onset of severe respiratory distress, radiographic evidence of , and died shortly thereafter. Dx: Paragonimus cyst in lung; pleural reaction is to trematode eggs--probably released by PB-RESP-56 Feline Paragonimus kellicotti 03-D263-C rupture of the parasitic cyst, that may have caused the pneumothorax and acute respiratory distress. YB111329 8 week old miniature pinscher dog. Group of pups began coughing 4-5 days ago, some anorexia. Condition has worsened despite treatment with Clavamox. This pup was presented in severe dyspnea, euthanized. Gross: severe consolidation of ventral lobes, did not float in formalin, section from caudal lobe is more normal. HISTO: One section of lung is edematous but otherwise normal. However, the other three sections contain similar lesions of bronchopneumonia. The alveoli and bronchioles are completely filled with large numbers of neutrophils and relatively scant fibrin. These neutrophils are non-necrotic in most areas, although an area of leukocyte necrosis is present adjacent to the pleura in one area. Numerous bacteria are present in this exudate, and bacteria are frequently adherent to the apical surface of the bronchiolar epithelium. These bacteria are Gram negative, based on the B&H and B&B stains. This lesion is not associated with any necrosis or attenuation of the epithelium. There is early hypertrophy of fibroblasts in the adjacent connective tissue, but no visible collagen production as yet. Histologic lesions are not present in the sections of heart. SUPPURATIVE BRONCHOPNEUMONIA WITH BACTERIA ADHERENT TO BRONCHIOLAR EPITHELIUM (PROBABLY BORDETELLA) The lesions are of bacterial bronchopneumonia and there is no evidence of bronchiolar or alveolar epithelial injury to suggest underlying viral infection. Bacteria adherent to the bronchiolar epithelium is a very prominent feature of these lesions, and is suggestive of Bordetella bronchiseptica infection. The diagnosis was confirmed by PCR (2008-1-25, see jpg) using Fla2 and Fla4 PB-RESP-57 Dog Bordetella--suppurative bronchiolitis and bronchopneumonia D06-119 primers to flagellin gene of B. bronchiseptica. D06-119. YB173800.

Page 8 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details Lungworms (Filaroides or Andersonstrongylus), dog also has laryngeal neuropathy with muscle atrophy, idiopathic suppurative meningoencephalitis with fibrinoid change in vessels, possible multi-organ vasculopathy, adrenocortical adenoma. Presented for acute respiratory distress due to laryngeal paralysis, these lesions are presumably incidental. Gross: The caudal lung lobes are diffusely slightly firm (pulmonary edema), and the right middle lung lobe is firm and dark red (possible pneumonia). Histo: Alveoli and small airways contain rare plant material (evidence of aspiration) in a patchy distribution associated with moderate aggregates of 5-20 pulmonary alveolar macrophages with foamy vacuolated cytoplasm and black phagocytosed granular debris. Alveoli additionally contain amorphous strongly eosinophilic fluid (high protein edema). Multifocally, aggregates of nematode parasites are present within the alveoli both subpleurally and within lung parenchyma in all examined sections of lung. Parasites are 50-100 microns in diameter with a 5-micron thick lightly eosinophilic cuticle, a coelom lined by platymyarian musculature, single gut lined by syncitial cells, and reproductive tract that contains embryos and eggs (indicative of a Strongyle, probably Filaroides hirthi or Andersonstrongylus milksi). No inflammation surrounds viable worms, and rarely nematodes are degenerate and are surrounded by PB-RESP-58 Dog Lungworm- Filaroides hirthi or Andersonstrongylus milksi 06-27057 moderate infiltrates of eosinophils and macrophages. YB173536. The abnormal tissue in the thorax is inflamed granulation tissue, which forms disorganized fronds of immature well-vascularized congested connective tissue. This contains large numbers of foamy macrophages as well as lymphocytes and plasma cells. With the Fite's modified acid-fast stain, there are rare extracellular clusters of pink-staining filamentous bacteria. Mesothelial cells covering the surface of the mass are hypertrophied. The section of lung is markedly atelectatic, and contains a similar reaction on the surface, although it is more dominated by lymphocytes and granulation tissue with only patchy aggregates of macrophages. PROLIFERATIVE AND GRANULOMATOUS PLEURITIS WITH NOCARDIA BACTERIA This condition is most commonly seen in young outdoor dogs, and is thought to represent pleural infection secondary to penetrating injury such as from migrating grass awns. However, foreign material is not found in the majority of cases. Nocardia and Actinomyces are typical isolates from such lesions, and the PB-RESP-59 Dog Nocardia pyogranulomatous and proliferative pleuritis D06-124 partially acid fast staining pattern confirms the diagnosis of nocardial pleuritis. PB-RESP-60 Dog Atelectasis, secondary to pneumothorax D05-139. Atelectasis, secondary to pneumothorax. Also anthracosis, focal hemorrhage. Dog was attacked and shaken by another dog. The lung is markedly congested and edematous, and close inspection reveals many thin hyaline membranes lining the surface of the alveoli. Alveolar hemorrhage is present but mild. This is an example of acute respiratory distress syndrome, probably as a result of trauma, PB-RESP-61 Dog Acute respiratory distress syndrome, traumatic 04-60164-A asphyxiation, or both. Young adult dog with progressive dyspnea. Lesions in the lung are diffuse. The alveolar septa are diffusely but only moderately thickened by collagenous connective tissue, which is highlighted by the Masson stain. Alveoli are filled with neutrophils and macrophages, and there is variable proliferation of type 2 pneumocytes, and infrequent syncytia. The epithelium of small bronchioles is attenuated and the lumens contain neutrophils and PB-RESP-65 Dog Pulmonary fibrosis. HE D06-003 macrophages. In contrast, the larger bronchioles appear normal. PB-RESP-69 Elk/red deer hybrids Tuberculosis 06-58499-2 Tuberculosis. 40L RtrphLN PB-RESP-70 Elk/red deer hybrids Tuberculosis--ZN stain of above. 06-58499-2 Tuberculosis. 40L RtrphLN Mature cat. Histo: Mass—The main mass is composed of variable amounts of fibrous tissue and granulation tissue. There is infiltration by lymphocytes and plasma cells with formation of lymphoid aggregations, areas of hemorrhage, and numerous dilated glands filled with secretion and degenerative neutrophils. The overlying hyperplastic epithelium is composed of psuedostratified ciliated epithelial cells. Tissue from bulla: This tissue is composed of mildly hyperplastic ciliated pseudostratified epithelium with numerous goblet cells overlying subepithelial tissues that have been infiltrated by lymphocytes, plasma cells and occasional neutrophils. Internal ear canal: This small fragment consists of keratinized squamous epithelium with mild infiltration of the superficial dermis with lymphocytes and plasma cells. Dx: Nasopharyngeal polyp, Mild chronic otitis externa PB-RESP-73 Cat Nasopharyngeal polyp 03-17649 and media

Page 9 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 15 month old dog, four month history of cough and diarrhea with no response to treatment, weight loss, dyspnea; radiographs reveal multiple 2-cm densities throughout the lungs; CBC shows leukocytosis and eosinophilia; a ecropsy: consolidation of left caudal lung, other lobes and variable size masses with very little normal lung tissue, mediastinal lymph node firm and enlarged. Histology: The sections of lung contains poorly demarcated coalescing nodules that occupy most of the tissue in the sections. These nodules contain a dense infiltrate of neoplastic round cells that are arranged as sheets, and often tend to cluster around blood vessels and obscure the wall of the blood vessels. The neoplastic cells are round cells with discrete borders, scant eosinophilic cytoplasm, round nuclei with finely clumped chromatin and indistinct nucleoli, prominent 3-fold anisokaryosis, and a relatively high mitotic rate at 1 per high-power field. Many of the neoplastic cells contain multiple nuclei. Occasional neoplastic cells contain two adjacent nuclei of equal size containing large nucleoli, resulting in an "owls eye" appearance. In some areas, the neoplastic cells fill the lumen of small blood vessels, and are occasionally enmeshed in a network of fibrin. A relatively abundant immature fibrous stroma is haphazardly intermingled with the neoplastic cells. Extensive necrosis is present in some areas of the tumor. The architecture of the lymph node is barely recognizable, due to extensive infiltration of a similar infiltrate of neoplastic cells. Pulmonary angiocentric lymphoma (lymphomatoid granulomatosis) with metastasis to lymph PB-RESP-76 Dog Lymphomatoid granulomatosis D05-07 node. The lung contains multifocal areas in which alveoli are filled by numerous nematode eggs (some of which are embryonated) and curved or coiled larva. I can't see any adults. There is a mild response of macrophages and lymphocytes, but more prominent formation of smooth muscle within alveolar septa. Alveoli are edematous. PB-RESP-88 Feline Aelurostrongylus 62061 Pulmonary arteries are prominent due to medial hypertrophy, and there is mucus hyperplasia in the small PB-RESP-93 Bovine Bovine tuberculosis 230-80 3 year old German shepherd. Presented for and vomiting frank blood. Large bulla identified on rads and CT in cranial part of left cranial lobe, with infiltrates of entire left cranial lung. Resected left lung lobe, submitted both. Bulla had grey-green lining. GROSS: 4 cm diameter raised nodule with a firm fibrous capsule. On cut section the nodule is cavitated and empty except for a small focus of soft, white to tan, material adherent to the inner capsule. All the remaining lung is congested, heavy and firm. HISTO: Cavitated mass (“Bulla”) (slide 1): The wall is approximately 7 mm thick and the internal border is composed of a plaque of densely packed fungal mycelia. The organism is hyphal, hyaline and is about 5 microns in diameter, septate, and parallel sided (Aspergillus sp.). The wall progresses from a layer of amorphous hypereosinophilic matrix with widely separated strands of collagen and cellular debris to a layer of neutrophils and karyorrhectic debris surrounded by large numbers of macrophages, with fewer plasma cells and lymphocytes, and an outermost layer of mature and organized fibrous connective tissue with numerous dissecting plump blood vessels, large clusters of perivascular lymphocytes and plasma cells and multifocal hemorrhage (granulation tissue). Peripheral lung tissue in close approximation to the bulla consists of alveoli containing abundant blood, amorphous eosinophilic material, foamy macrophages, plasma cells, lymphocytes and neutrophils and type II pneumocyte hyperplasia. Occasionally small vessels contain luminal partially occlusive hypereosinophilic amorphous material (thrombi). The mesothelial cells of the pleural surface are plump and low cuboidal. Lung (the other lobe) (slide 6): Large airways (bronchi and bronchioles) are surrounded by very large numbers of macrophages with fewer plasma cells, lymphocytes and neutrophils (granulomas encompassing approximately 15% of the parenchyma), which displace peri-bronchiolar alveoli. Occasionally large airways are filled with red blood cells, sloughed epithelium and necrotic debris. The bronchiolar epithelium is stretched thin into attenuated spindle shaped cells or 13-013296-1,6 Dog Aspergilloma and chronic fungal bronchitis multifocally lacking (ulceration).

Page 10 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 8 year old Ragdoll cat. 3 day history of anorexia, lethargy, heart murmur grade III/IV. Referred to cardiologist. Gross: Bilaterally the lungs are firm, red and heavy with areas of consolidation mostly around the mainstem bronchi. On cut surface the lungs exude moderate amounts of bloody liquid mixed with froth. Within the pleural space there are approximately 15 mL of straw colored serous liquid. Within the pericardial sac there is approximately one mL of similar liquid. Gross dx: interstitial pneumonia. Histo: (Acute diffuse interstitial pneumonia (diffuse alveolar damage) with multifocal bronchiolar epithelial necrosis). There is acute diffuse alveolar damage. Alveolar septae are thickened due to congestion, edema and fibrin. There is multifocal alveolar septal necrosis. Alveolar lumens contain strands of fibrin with occasional hyaline membranes, alveolar macrophages (with occasional erythrocytophagia), scattered neutrophils, and necrotic cells. Rare areas of early type II pneumocyte hyperplasia. There is attenuation and loss of bronchiolar epithelium; remaining epithelial cells are pleomorphic. Some affected bronchioles contain fibrin exudates in the lumen. Some bronchiolar epithelial cells have prominent intranuclear structures (reactive nucleoli, no definitive inclusions). Some bronchioles are unaffected. Bacteriology: no bacterial growth. IHC for influenza and toxoplasmosis negative. RT-PCR for influenza A virus positive on lung (H1N1, neg for H3N2) and negative on allantoic fluid. No virus 14-004320-4 Cat Influenza H1N1 isolated in cell culture. The clinical veterinarian was not aware of any human illness in the household. 70514-6 Dog Olfactory neuroblastoma Tumor? In brain? Background is synaptophysin positive but the cells are negative Inclusion body rhintis-("cytomegalovirus") SuHV-2. Piglet, 35 days old, incidental finding, PM: nasal passages filled with discharge. Diffuse lymphocytic rhinitis. The additional lesions are not numerous, but are found in several areas including the nubbin protruding from the turbinate near its junction with the septum. In these areas, some of the epithelial cells lining the mucosal glands are enlarged up to 30-micron-diameter, with pale vacuolated cytoplasm and a large (15 micron) blue-purple smudgy nucleus. These represent cytomegalic cells 00-015445-4 Pig Inclusion body rhintis with intranuclear inclusions. 7-year-old Pug. Left cranial lung lobe torsion. Lung: Two samples of lung are examined on two slides, both have similar histologic changes. Almost all of the alveoli and bronchioles are filled with or expanded by erythrocytes, admixed with fibrin and neutrophils (pulmonary hemorrhage). The outlines of alveolar septa, bronchioles, and pulmonary vessels are visible; however, cellular and nuclear detail are absent ( necrosis). In some areas the visceral pleura is expanded up to twenty fold by haphazardly arranged plump fibroblasts, erythrocytes, fibrin, and neutrophils (early granulation tissue). The sample taken from the mass (Slide 1) has similar changes but with larger lakes of free erythrocytes, particularly in subpleural regions (). Lung, surgical margin: A single sample of lung is examined on one slide. There is collapse of alveolar spaces (atelectasis) accounting for 30 % of the parenchyma and another 20 % of alveolar spaces are blood-filled. Small arterioles within alveolar septa are prominent and blood-filled (pulmonary congestion). Within non-aerated regions, there is patchy attenuation and loss of bronchiolar epithelial cells with occasional fibrin deposits (bronchiolar necrosis). DIAGNOSIS: 1. Lung: Pulmonary infarction and hemorrhage (consistent with lung lobe torsion), with reactive pleuritis 2. Lung: 14-060107-2 Dog Lung lobe torsion, infarction and hemorrhage

Page 11 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 2 year old pet rat. GROSS: The anterior and posterior lobes of the right lung are obscured by multiple, coalescing, lobulated, raised, tan nodules. Approximately 80% of the surface of left lung lobe contains a generalized, well demarcated, flat, irregular, alternating dark red and tan pattern and the surface of the adjacent parietal pleural contains innumerable, tan, gritty, pinpoint nodules. HISTO: Right lung (slide 05): Filling large airways and replacing approximately 90% of the adjacent parenchyma there are numerous, multifocal to coalescing, well circumscribed, unencapsulated nodules ranging from 5mm to 10mm in diameter. These nodules are composed of dense sheets of degenerative neutrophils and large, foamy macrophages surrounding extensive islands of necrotic cellular debris. Throughout the sections, multiple airways contain proteinaceous fluid and foamy macrophages, and there are multifocal peribronchial and peribronchiolar accumulations of large numbers of lymphocytes and plasma cells. Within the remaining lung parenchyma, alveoli are frequently collapsed or filled with cellular debris, there is evidence of generalized type 2 pneumocyte hyperplasia, and there is marked interstitial fibrosis. Right lung (Warthin-Starry stain, slide 05): Frequently lining ciliated bronchiolar epithelium, there are aggregates of filamentous, argyrophilic bacilli (consistent with Cilia-Associated Respiratory Bacillus). Left lung (slide 04): There is moderate autolysis. There is patchy atelectasis, in addition to a moderate, generalized accumulation of proteinaceous fluid and large foamy macrophages within alveolar spaces (pulmonary edema). Frequent macrophages also contain a moderate to abundant amount of red-brown granular pigment (hemosiderin). In some areas, alveolar septa are moderately thickened by fibrous connective tissue and there are variably increased numbers of lymphocytes and plasma cells within the interstitium. Affecting approximately 5% of the sections examined there are multifocal, well demarcated, variable sized 100um to 250um diameter, granulomatous nodules. Frequently within these nodules there are empty acicular clefts (cholesterol clefts), multinucleated giant cells and yellow granular cytoplasmic pigment within macrophages 14-063126-5 Rat CAR bacillus (suspect lipofucin). 2 year old pet rat. GROSS: The anterior and posterior lobes of the right lung are obscured by multiple, coalescing, lobulated, raised, tan nodules. Approximately 80% of the surface of left lung lobe contains a generalized, well demarcated, flat, irregular, alternating dark red and tan pattern and the surface of the adjacent parietal pleural contains innumerable, tan, gritty, pinpoint nodules. HISTO: Right lung (slide 05): Filling large airways and replacing approximately 90% of the adjacent parenchyma there are numerous, multifocal to coalescing, well circumscribed, unencapsulated nodules ranging from 5mm to 10mm in diameter. These nodules are composed of dense sheets of degenerative neutrophils and large, foamy macrophages surrounding extensive islands of necrotic cellular debris. Throughout the sections, multiple airways contain proteinaceous fluid and foamy macrophages, and there are multifocal peribronchial and peribronchiolar accumulations of large numbers of lymphocytes and plasma cells. Within the remaining lung parenchyma, alveoli are frequently collapsed or filled with cellular debris, there is evidence of generalized type 2 pneumocyte hyperplasia, and there is marked interstitial fibrosis. Right lung (Warthin-Starry stain, slide 05): Frequently lining ciliated bronchiolar epithelium, there are aggregates of filamentous, argyrophilic bacilli (consistent with Cilia-Associated Respiratory Bacillus). Left lung (slide 04): There is moderate autolysis. There is patchy atelectasis, in addition to a moderate, generalized accumulation of proteinaceous fluid and large foamy macrophages within alveolar spaces (pulmonary edema). Frequent macrophages also contain a moderate to abundant amount of red-brown granular pigment (hemosiderin). In some areas, alveolar septa are moderately thickened by fibrous connective tissue and there are variably increased numbers of lymphocytes and plasma cells within the interstitium. Affecting approximately 5% of the sections examined there are multifocal, well demarcated, variable sized 100um to 250um diameter, granulomatous nodules. Frequently within these nodules there are empty acicular clefts (cholesterol clefts), multinucleated giant cells and yellow granular cytoplasmic pigment within macrophages 14-063126-5 Rat CAR bacillus-WS silver stain (suspect lipofucin).

Page 12 of 13 Key to respiratory pathology Aperio histology cases - Diagnoses

Title Species Diagnosis Case number Case details 2.5 month old foal with a 3-week history of pyrexia responsive to antimicrobials. On the most recent bloodwork from the regular veterinarian, white blood cell count was elevated at 26.3, urea was elevated at 46, and creatinine was elevated at 650; regular veterinarian suspected renal failure and the foal was referred into the OVC-HSC. Treated at OVC with ceftiofur and IV fluids. Urea 60 and Creatinine 600 +- on the day of euthanasia. GROSS Lungs: Approximately 60% of the lung fields bilaterally are effaced by large, coalescing abscesses that on cut surface have thick fibrous capsules and ooze copious purulent material. There are multiple fibrous, pleural adhesions between the lateral thoracic walls and the pericardial sac. The trachea bronchial lymph nodes are enlarged and are mottled tan red on cut surface. The caudal portion of the lungs is unaffected by the abscessation, but they generally lack aeration, are heavy, wet, and fail to collapse. There is approximately 500 ml of red tinged fluid in the pleural cavity. HISTO: 100% of the lung in these sections is affected by the following lesions. There are multiple coalescing and extensive regions scattered throughout these sections where the pulmonary parenchyma is completely effaced by large numbers of degenerate neutrophils admixed with hypereosinophilic amorphous debris, fibrin, and pyknotic chromatin debris (caseous necrosis). These areas of necrosis are often partially surrounded by eosinophilic fibrous matrix (collagen), and immature plump fibroblasts. In areas where the parenchyma is relatively preserved, the lumens of the bronchi and terminal bronchioles are filled with large numbers of degenerate neutrophils and fibrin. The epithelial cells lining these airways are jumbled, basophilic, dysplastic, and, in some areas, attenuated. Remaining alveolar spaces are variably filled with large alveolar macrophages that have copious, hypereosinophilic, granular cytoplasm and often pyknotic nuclei. Alveoli also contain degenerate neutrophils and fibrin, and alveolar walls are often lined by plump to cuboidal epithelial cells (type II pneumocyte hyperplasia). In some areas, alveolar walls are markedly thickened by fibrous matrix and plump fibroblasts. There is generalized marked expansion of the visceral pleura and interlobular septa where the 14-049132-4 Foal Rhodococcus: lung, colon collagen fibers are markedly separated by edema. 30016576-16 Dog Angiostrongylus Acta Parasitol. 2017 Mar 1;62(1):221-224. Lethal Angiostrongylus vasorum infection in a dog

Page 13 of 13