JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2017

P-N05

 

Slide A:

Signalment (JPC #2237659):  A 6½-year-old Bernese mountain dog

HISTORY:  Unknown

HISTOPATHOLOGIC DESCRIPTION:  Lung:  Effacing approximately 95% of the pulmonary architecture and abutting the moderately thickened pleura is a poorly demarcated, infiltrative, densely cellular neoplasm composed of round to spindle cells (histiocytes) arranged haphazardly in short streams and variably sized sheets separating the pre-existing pulmonary fibrovascular matrix.  Neoplastic cells have variably distinct cell borders, moderate to abundant eosinophilic granular and often microvacuolated to foamy cytoplasm, irregularly round to reniform nuclei with finely stippled chromatin and 1-3 variably distinct nucleoli.  Anisocytosis and anisokaryosis are marked.  Mitotic rate is regionally variable with up to 5 per high power field in the most mitotically active areas and with occasional bizarre mitotic figures.  Within the neoplasm, there are numerous neoplastic multinucleated giant cells containing up to 30 nuclei which occasionally exhibit nuclear molding.  There is multifocal scattered phagocytosis of leukocytes and erythrocytes by neoplastic cells; many degenerate neutrophils, lymphocytes, and plasma cells; mixed areas of lytic and coagulative necrosis; multifocal invasion of vessels by neoplastic cells; rare single cell necrosis; and few ectactic lymphatics.  Multifocally the pleura is lined by reactive mesothelium and expanded up to 500 microns thick by fibrous connective tissue (fibrosis) and fewer inflammatory cells.

MORPHOLOGIC DIAGNOSIS:  Lung:  Histiocytic sarcoma, Bernese mountain dog, canine.

CONDITION:  Disseminated histiocytic sarcoma

Slide B:

Signalment:  13-year-old, female, domestic long hair, feline

HISTORY:  The cat had a 5-day history of increased respiration, with 3-4 days of rapid shallow breathing and 2 weeks of weight loss. The owners had noticed a recent change in the cat's vocalization. Thoracic radiographs revealed a diffuse bronchointerstitial pattern throughout the lungs. There was no response to treatment with bronchodilators or glucocorticoids.

HISTOPATHOLOGIC DESCRIPTION:  Lung:  Throughout the section of lung, large numbers of alveoli and alveolar ducts contain densely packed, round to slightly spindle-shaped cells with variably distinct cell borders that completely fill the alveolar and ductal lumens. The cells form dense rounded clusters within alveoli and are often arranged in a lightly streaming pattern. The infiltrating cells have a histiocytic appearance, characterized by a moderate amount of lightly eosinophilic to pale basophilic cytoplasm, which is sometimes lightly vacuolated, and cell nuclei that are round to oval, often eccentrically placed and slightly indented, and which contain variably condensed basophilic chromatin. Mitotic figures are rare (<1 per 400x field). Some alveoli also contain individual or small central clusters of macrophages with abundant, highly vacuolated, foamy cytoplasm and small condensed nuclei. Many alveoli are segmentally lined by prominent, cuboidal epithelial cells (type II pneumocyte hyperplasia). The smooth muscle within alveolar septa is markedly thickened in many areas (smooth muscle hyperplasia). Peribronchiolar and peribronchial lymphocytes are prominent, and clusters of densely packed lymphocytes with lesser numbers of plasma cells are also scattered throughout the section. Many alveoli contain abundant eosinophilic proteinaceous fluid (edema). In some areas the normal alveolar architecture is replaced by thin interlacing bands of collagenous tissue (interstitial fibrosis), with moderate numbers of lymphocytes and plasma cells and multifocal areas of mild hemorrhage. Alveolar septa are lost in many areas resulting in enlarged, confluent air spaces (emphysema).

MORPHOLOGIC DIAGNOSIS:  Lung:  Alveolar and bronchiolar histiocytosis, proliferative, severe, diffuse with smooth muscle hyperplasia, type II pneumocyte hyperplasia and moderate lymphoplasmacytic and histiocytic inflammation

CONDITION:  Pulmonary Langerhans cell histiocytosis

 

GENERAL DISCUSSION:

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPE FINDINGS:

ULTRASTRUCTURAL FINDINGS:

DIFFERENTIAL DIAGNOSIS:

Histiocytic proliferative disorders:

 COMPARATIVE PATHOLOGY:

 

Cell of origin

Disease(s)

Immunohistochemistry

Positive

Negative

Langerhans cell

Canine cutaneous histiocytoma; Feline PCLH

E-cadherin, CD1a, CD11a/CD11c/CD18, MHC II

Thy-1, CD4

Interstitial dendritic cell

Canine reactive histiocytoses

Thy-1, CD4, CD1a, CD11c/CD18, MHC II

E-cadherin

Interstitial dendritic cell

HS complex, FPH

CD1a, CD11c/CD18, MHC II

Thy-1, CD4,

E-cadherin

Macrophage (splenic red pulp)

Hemophagocytic HS (dogs and cats)

CD11d/CD18, MHCII

CD1a, CD11c

 

REFERENCES:

  1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:103,110-111,167-168,183.
  2. Busch MDM, Reilly CM, Luff JA, Moore PF. Feline pulmonary Langerhans cell histiocytosis with multiorgan involvement. Vet Pathol. 2008;45(6):816-824.
  3. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Limited; 2016:498-499.
  4. Constantino-Casas F, Mayhew D, Hoather TM, Dobson JM. The clinical presentation and histopathologic-immnuohistochemical classification of histiocytic sarcoma in the Flat Coated Retriever. Vet Pathol. 2011;48:764-771.
  5. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier Limited; 2016:159-160.
  6. Craig LE, Thompson KG. Tumors of joints. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, Iowa: Iowa State Press; 2017:341-345.
  7. Fry MM, McGavin MD. Bone marrow, blood cells and the lymphatic system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Mosby; 2017:795-796.
  8. Hao X, Fredrickson TN, Chattopadhyay SK, et al. The histopathologic and molecular basis for the diagnosis of histiocytic sarcoma and histiocyte-associated lymphoma of mice. Vet Pathol. 2010;47(3):434-445.
  9. Helie P, Kiupel M, Drolet R. Congenital cutaneous histiocytosis in a piglet. Vet Pathol. 2014;51(4):812-815.
  10. Hirako A, Sugiyama A, Sakurai M, et al. Cutaneous histiocytic sarcoma with E-cadherin expression in a Pembroke Welsh Corgi dog. J Vet Diagn Invest. 2015 Sep;27(5):589-95.
  11. Karim MR, Izawa T, Pervin M, et al. Cutaneous histiocytic sarcoma with regional lymph node metastasis in a Netherland dwarf rabbit (Oryctolagus cuniculus). J Comp Pathol. 2017 Feb - Apr;156(2-3):169-172.
  12. Marcinowska A, Constantino-Casas F, Williams T, et al. T lymphocytes in histiocytic sarcomas of flat-coated retriever dogs. Vet Pathol. 2017 Jul;54(4):605-610.
  13. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd. 2016:728-730.
  14. Moore PF. A review of histiocytic diseases of dogs and cats. Vet Pathol. 2014;51(1):167-184.
  15. Moore PF. Canine and feline histiocytic disorders. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, Iowa: Iowa State Press; 2017:322-335.
  16. Moore PF, Affolter VK. Canine hemophagocytic histiocytic sarcoma: A proliferative disorder of CD11d+ macrophages. Vet Pathol. 2006;43:632-645.
  17. Ogihara K, Itoh T, Mizuno Y, et al. Disseminated histiocytic sarcoma in an African hedgehog (Atelerix albiventris). J Comp Pathol. 2016 Nov;155(4):361-364.
  18. Thongtharb A, Uchida K, Chambers JK, Nakayama H. Variations in histiocytic differentiation of cell lines from canine cerebral and articular histiocytic sarcomas.  Vet Pathol. 2017 May;54(3):395-404.
  19. Valli VEO, Kiupel M, Bienzle D. Hematopoietic system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier Limited; 2016:222,243-255.
  20. Van kuijk L, van Ginkel K, de Vos JP, et al. Peri-articular histiocytic sarcoma and previous joint disease in Bernese mountain dogs. J Vet Intern Med. 2013;27(2):293-299.
  21. Van Nieuwenhuijze AE, Coghill E, Gray D, et al. Transgenic expression of GM-CSF in T cells causes disseminated histiocytosis. Am J Pathol. 2014;184(1):184-199.


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