Malignant fibrous histiocytoma

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2019

I-N27

 

 

 

SLIDE A

Signalment (JPC# 3044519): Hooded crossbred rat, rodent

 

HISTORY: Unspecified

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Infiltrating the subcutis; separating, surrounding, and replacing skeletal muscle; and extending to cut borders is an unencapsulated, well demarcated, infiltrative, densely cellular neoplasm composed of round to spindle cells arranged in broad sheets on a moderate preexisting fibrovascular stroma. Neoplastic cells have variably distinct cell borders; a moderate to abundant amount of eosinophilic, finely fibrillar to occasionally microvacuolated cytoplasm; and a round, oval, or reniform nucleus with finely stippled chromatin and one distinct nucleolus. The mitotic count is regionally variable with up to 3 per 400x high power field. There is moderate anisocytosis and anisokaryosis. Multifocally, there are moderate numbers of neoplastic multinucleated giant cells up to 100 µm in diameter with up to 30 nuclei. There is scattered single cell necrosis as well as large areas of coagulative necrosis characterized by retention of cellular architecture and loss of differential staining admixed with foci of lytic necrosis characterized by eosinophilic and cellular debris admixed with numerous cholesterol clefts. Multifocally there are hemosiderin-laden macrophages and hematoidin crystals. Multifocally, moderate numbers of myofibers are shrunken and angular with deeply eosinophilic sarcoplasm (atrophy); less commonly swollen with vacuolated sarcoplasm and loss of cross striations (degeneration); or rarely shrunken or fragmented with pyknotic nuclei (necrosis).

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Cutaneous histiocytic sarcoma, Hooded crossbred rat, rodent.

 

SLIDE B

Signalment (JPC# 1918993): Cat, breed and age unspecified

 

HISTORY: Tissue from a multilobulated mass in the lumbar region

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Infiltrating the subcutis and deep dermis, elevating the epidermis, and extending to cut borders is an unencapsulated, densely cellular, multilobulated neoplasm composed of spindle cells arranged in long, interlacing streams and bundles on a moderate fibrovascular stroma; lobules are separated by broad bands of mature collagen. Neoplastic cells have indistinct borders and a moderate amount of eosinophilic, fibrillar cytoplasm. Nuclei are elongate with finely stippled chromatin and have 1-2 variably distinct nucleoli. There is mild anisocytosis and anisokaryosis. Admixed with spindle cells are moderate numbers of more round, pleomorphic, multinucleated giant cells up to 100um in diameter with up to 10 nuclei and often prominent nucleoli. The mitotic count averages 3 per 10 400x high power fields. Neoplastic cells surround a large, focally extensive area of drop-out, lytic necrosis, and artifactual separation. Multifocally within the neoplasm there are variably sized, up to 2mm diameter, areas of lytic necrosis characterized by loss of architecture with replacement by eosinophilic and cellular debris as well as hemorrhage, fibrin, and edema. At the periphery of the neoplasm there are often perivascular aggregates of lymphocytes with fewer plasma cells. The surrounding connective tissue and dermis are loosely arranged and expanded by clear space, and lymphatics are mildly ectatic (edema).

 

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Undifferentiated pleomorphic sarcoma (previously known as malignant fibrous histiocytoma), breed not specified, feline

 

SYNONYMS: Malignant fibrous histiocytoma, malignant giant cell tumor of soft parts, extraskeletal giant cell tumors, dermatofibrosarcomas, anaplastic sarcoma with giant cells

 

GENERAL:

·      Histiocytic sarcoma (HS) complex includes several subtypes of histiocytic sarcoma and feline progressive histiocytosis (FPH) (also see H-N03)

·      Subtypes: Hemophagocytic HS, articular/periarticular HS, central nervous system HS, dendritic cell leukemia

·      Typically, interstitial dendritic cell (iDC) origin (exception: hemophagocytic histiocytic sarcoma is of macrophage origin)

·      Histiocytic sarcoma can be localized or disseminated (disseminated HS was previously known as malignant histiocytosis); these two forms are histologically and immunophenotypically identical

·      Disseminated histiocytic sarcoma (malignant histiocytosis): May represent metastasis of primary lesion or multicentric neoplastic transformation of histiocytes

·      Multicentric (primary neoplasm) in spleen, lung, bone marrow; +/- dissemination to liver, lymph nodes, brain (meninges), synovial tissues of limbs, rarely affects skin

·      Major cutaneous types of HS complex (2): Localized histiocytic sarcoma (LHS) and feline progressive histiocytosis (FPH)

·      Localized histiocytic sarcoma

·      More common in dogs, rare in cats

·      Rapidly growing, malignant, dermal or subcuticular neoplasm; often periarticular

·      Locally invasive to the joint capsule, tendons, and muscles of the region

·      Feline progressive histiocytosis

·      Most common histiocytic disease in cats

·      Despite the name, thought to be a low-grade histiocytic sarcoma originating from cutaneous interstitial dendritic cells (similar IHC staining profile)

·      Indolent form of localized histiocytic sarcoma, originates in skin of cats

·      Malignant fibrous histiocytoma (MFH or giant cell tumor of soft parts):

·      Immunohistochemical and ultrastuctural findings suggest that MFH is really a nonspecific collection of anaplastic mesenchymal / non-mesenchymal tumors

·      Those that cannot be further classified as specific soft tissue tumors (such as HS) are simply termed pleomorphic undifferentiated (or anaplastic) sarcoma

 

PATHOGENESIS:

Localized histiocytic sarcoma

·      Interstitial dendritic cell (iDC) origin; express CD1a, MDCII, and CD11c/CD18, CD204 (+/-), Iba1

·      Exception: hemophagocytic histiocytic sarcoma is macrophage origin; express CD1a (+/-), CD11d/CD18 (dog), CD204, Iba1

·      CD4 negative; in contrast to canine reactive histiocytosis

·      Bernese Mountain dogs, Rottweilers, golden retrievers, and flat-coated retrievers are predisposed

·      Bernese Mountain dogs and flat-coated Retrievers have abnormalities in tumor suppressor gene loci (CDKN2A/B, RB1, and PTEN)

Feline progressive histiocytosis

·      iDC origin

·      Seen more in female middle aged to older cats

 

TYPICAL CLINICAL FINDINGS:

Localized histiocytic sarcoma

·      Depend on the organ involved; often anorexia, weight loss, and lethargy

·      Solitary or multiple lesions

·      Hyperferritinemia

·      Possible mild nonregenerative anemia and hypercalcemia

·      Hemophagocytic form: Lacks skin lesions; marked, regenerative, hemolytic anemia and thrombocytopenia

Feline progressive histiocytosis

·      Lesions may wax and wane, but poor long-term prognosis; complete regression is not a feature

 

TYPICAL GROSS FINDINGS:

Localized histiocytic sarcoma

·      Dogs: Usually occurs on an extremity or in close proximity to a joint

·      White, multinodular tissue that invades and destroys surrounding tissue

Feline progressive histiocytosis

·      Solitary or more commonly multiple firm, nonpruritic, nonpainful, alopecic and ulcerated papules, nodules, and plaques

·      Commonly on the head, trunk, and lower extremities

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Localized histiocytic sarcoma

·      Mixture of pleomorphic, anaplastic, plump, round histiocytic cells, and multinucleated histiocytic giant cells

·      Marked cytologic atypia with high mitotic rate and numerous bizarre mitotic figures

·      Abundant eosinophilic cytoplasm

·      Large oval to indented or twisted vesicular nuclei

 

Feline progressive histiocytosis

·      Diffuse dermal or subcuticular infiltrate of morphologically normal histiocytes; about 40% exhibit epitheliotropism (intraepidermal accumulations of histiocytic clusters)

·      Variable mitotic rate

·      In late stages may resemble LHS (pleomorphism, multinucleated giant cells, etc.)

 

ADDITIONAL DIAGNOSTIC TESTS:

Localized histiocytic sarcoma

·      Immunoreactivity: CD1, CD11c/CD18 MHC II, ICAM, CD163, CD204

·      Negative immunoreactivity: CD4, E-cadherin, COX-2, CD90 (Thy-1)

·      Increased Glut-1 immunoreactivity (hypoxia marker) (Abbondati Vet Pathol. 2013)

·      Iba1: marker of monocyte/macrophage lineage cells in canines and felines

·      Cannot differentiate macrophages or dendritic antigen presenting cells 

·      A recent study of histiocytic sarcomas in flat-coated retriever dogs (Marcinowska Vet Pathol. 2017) found that the associated lymphocytic infiltrate may demonstrate positive immunoreactivity for FoxP3 in neoplasia of soft tissue origin, and CD45RA in neoplasia of splenic origin (Treg population)

Feline progressive histiocytosis

·      Immunoreactivity: CD1a, CD11b/CD18, and MHC-II

·      Negative immunoreactivity: CD4, E-cadherin

·      +/- CD5 (50%)

 

DIFFERENTIAL DIAGNOSIS:

Localized histiocytic sarcoma

·      Cutaneous histiocytosis (I-M10)

·      Disseminated histiocytic sarcoma (malignant histiocytosis)- cutaneous involvement rare

·      Canine cutaneous histiocytoma (I-N22)

·      Wide variety of sarcomas

·      Idiopathic nodular dermatitis / panniculitis (I-M12, I-M17)

·      Granulomatous dermatitis caused by infectious agents (fungi, bacteria, parasites)

Feline progressive histiocytosis

·      Atypical large cell lymphoma

·      Dermatitis (generalized inflammatory)

 

COMPARATIVE PATHOLOGY:

·      Horses: Hind limb is the most common site in older horses

·      Mice: Histiocytic sarcoma is the second most significant hematopoietic neoplasm in laboratory mice (second to lymphoma); especially common is some strains of laboratory mice (aged B6 and SJL); renal proximal tubules may contain hyaline droplets associated with histiocytic sarcomas

·      Rats: Occur most often in SD rats, commonly in Sprague Dawley rat, primarily in animals older than 12 months

·      Hamsters: Reported in 5/15 hamsters studied in Taiwan, 2010-2017 (Tuan, J Comp Pathol. 2018)

·      Ferret: Histiocytic sarcoma in the ferret is a rare, but highly aggressive, tumor commonly found in the spleen (Thongtharb J Vet Diag Invest. 2016)

·      African hedgehog: One case report of disseminated histiocytic sarcoma (Ogihara J Comp Pathol. 2016), one case report on primary histiocytic sarcoma in the brain (Ogihara J Comp Pathol. 2017)

·      Netherland Dwarf rabbit: Case report of cutaneous histiocytic sarcoma with metastasis to regional lymph node (Karim J Comp Pathol. 2017)

·      Hippopotamus: Case report of system histiocytic sarcoma in a 37-year-old, captive common hippopotamus (Fachini J Zoo Wildlife Med. 2016)

·      Wildlife: Has been reported in Bactrian camel, slow Loris, Crowned lemur, and Gray mouse lemur

 

REFERENCES:

1.    Abbondati E, Del-Pozo J, Hoather TM, Constantino-Casas F, Dobson JM. An immunohistochemical study of the expression of the hypoxia markers Glut-1 and Ca-IX in canine sarcomas. Vet Pathol. 2013;50(6):1063-1069.

2.    Agnew D. Camelidae. In: Pathology of Wildlife and Zoo Animals. Eds. Terio KA, McAloose D, St. Leger J. San Diego, CA: Elsevier; 2018: 193.

3.    Barthold SW, Griffey SM, Percy DH. Mouse. In: Pathology of Laboratory Rodents and Rabbits, 4th Ed. Ames, IA: Wiley Blackwell; 2016: 103, 110-111, 167-168.

4.    Clarke LL, Kelly LS, et al. Atypical cytologic presentation of a histiocytic sarcoma in a Cavalier King Charles Spaniel dog. J Vet Diag Invest. 2017; 29(4): 541-543.

5.    Delaney MA, Treuting PM, et al. Rodentia. In: Pathology of Wildlife and Zoo Animals. Eds. Terio KA, McAloose D, St. Leger J. San Diego, CA: Elsevier; 2018: 513.e2.

6.    Fachini da Costa L, Malta MCC, et al. Systemic histiocytic sarcoma in a common hippopotamus (Hippopotamus amphibious). J Zoo and Wildlife Med. 2016; 47(2): 650-653.

7.    Gross TL, Ihrke PJ, et al. Other mesenchymal tumors. In: Skin Diseases of the Dog and Cat, 2nd Edition. Ames, IA: Blackwell Science Ltd; 2005: 806-812.

8.    Hirako A, Sugiyama A, Sakurai M, Ozaki K, Sakai H, Takeuchi T, Morita T, Moore PF. Cutaneous histiocytic sarcoma with E-cadherin expression in a Pembroke Welsh Corgi dog. J Vet Diagn Invest. 2015; 27(5):589-595.

9.    Ide T, Uchida K, Yumiko K, Kazuhiko S, Hiroyuki N. Pathological and immunohistochemical features of subdural histiocytic sarcomas in 15 dogs. J Vet Diagn Invest. 2011; 23:127-132.

10. Karim MR, Izawa T, et al. Cutaneous histiocytic sarcoma with regional lymph node metastasis in a Netherland Dwarf rabbit (Oryctolagus cuniculus). J Comp Pathol. 2017; 156: 169-172.

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12. Marcinowska A, Constantino-Casas F, et al. T lymphocytes in histiocytic sarcomas of flat-coated Retriever dogs. Vet Pathol. 2017; 54(4): 605-610.

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15. Ogihara K, Itoh T, Mizuno Y, Tamukai K, Madarame H. Disseminated histiocytic sarcoma in an African hedgehog (Atelerix albiventris). J Comp Pathol. 2016; 155: 361-364.

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18. Pierezan F, Mansell J, Ambrus A, Rodrigues Hoffmann A. Immunohistochemical expression of ionized calcium binding adapter molecule 1 in cutaneous histiocytic proliferative, neoplastic and inflammatory disorders of dogs and cats. J Comp Pathol. 2014;151(4):347-351.

19. Ramos-Vara JA, Miller MA. Immunohistochemical expression of E-cadherin does not distinguish canine cutaneous histiocytoma from other canine round cell tumors. Vet Pathol. 2011; 48(3):758-763.

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21. Thongtharb A, Uchida K, Chambers JK, Miwa Y, Murata Y, Nakayama H. Histological, and immunohistochemical features of histiocytic sarcoma in four domestic ferrets (Mustela putorius furo). J Vet Diagn Invest. 2016; 28(2):165-170.

22. Tuan YC, Wan RC, et al. Retrospective pathological studies of splenic lesions in domestic hamsters (Phodopus spp). J Comp Pathol. 2018; 164: 37-43.

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24. van Kuijk L, van Ginkel K, deVos JP, et al. Peri-articular histiocytic sarcoma and previous joint disease in Bernese mountain dogs. J Vet Intern Med. 2013; 27:293-299.

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