-
Philosophical Transactions of the Royal... Jul 2015Over 1.66 million humans (approx. 500/100,000 population rate) and over 4.2 million dogs (approx. 5300/100,000 population rate) are diagnosed with cancer annually in the... (Review)
Review
Over 1.66 million humans (approx. 500/100,000 population rate) and over 4.2 million dogs (approx. 5300/100,000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.
Topics: Animals; Breeding; Disease Models, Animal; Dog Diseases; Dogs; Female; Genome-Wide Association Study; Genomics; Germ-Line Mutation; Humans; Male; Neoplasms; Risk Factors; Species Specificity; Translational Research, Biomedical
PubMed: 26056372
DOI: 10.1098/rstb.2014.0231 -
The Oncologist Jul 2021Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell...
BACKGROUND
Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking.
METHODS
Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes.
RESULTS
Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen-activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance.
CONCLUSION
A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors.
IMPLICATIONS FOR PRACTICE
This study presents comprehensive genomic profiling results on 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs). MAPK pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCSs. In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytosis. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies.
Topics: Child; Dendritic Cell Sarcoma, Follicular; Dendritic Cells; Genomics; Hematopoietic Stem Cell Transplantation; Humans; Mutation; Neoplasm Recurrence, Local; Sarcoma
PubMed: 33904632
DOI: 10.1002/onco.13801 -
ILAR Journal 2014Domestic dogs are unique from other animal models of cancer in that they generally experience spontaneous disease. In addition, most types of cancer observed in humans... (Review)
Review
Domestic dogs are unique from other animal models of cancer in that they generally experience spontaneous disease. In addition, most types of cancer observed in humans are found in dogs, suggesting that canines may be an informative system for the study of cancer genetics. Domestic dogs are divided into over 175 breeds, with members of each breed sharing significant phenotypes. The breed barrier enhances the utility of the model, especially for genetic studies where small numbers of genes are hypothesized to account for the breed cancer susceptibility. These facts, combined with recent advances in high-throughput sequencing technologies allows for an unrivaled ability to use pet dog populations to find often subtle mutations that promote cancer susceptibility and progression in dogs as a whole. The meticulous record keeping associated with dog breeding makes the model still more powerful, as it facilitates both association analysis and family-based linkage studies. Key to the success of these studies is their cooperative nature, with owners, scientists, veterinarians and breed clubs working together to avoid the cost and unpopularity of developing captive populations. In this article we explore these principals and advocate for colony-free, genetic studies that will enhance our ability to diagnose and treat cancer in dogs and humans alike.
Topics: Animals; DNA Mutational Analysis; Disease Models, Animal; Dog Diseases; Dogs; Histiocytic Sarcoma; Male; Prostatic Neoplasms; Registries; Research; Species Specificity; Urinary Bladder Neoplasms
PubMed: 24936030
DOI: 10.1093/ilar/ilu017 -
The New England Journal of Medicine May 1990Between September 1983 and December 1988, we observed 16 cases of hematologic neoplasia associated with mediastinal germ-cell tumors. Twenty-eight similar cases have... (Review)
Review
Between September 1983 and December 1988, we observed 16 cases of hematologic neoplasia associated with mediastinal germ-cell tumors. Twenty-eight similar cases have been reported in the literature. A review of the clinical and cytogenetic details in these patients suggests that the hematologic neoplasia is not the result of cisplatin-based chemotherapy of the mediastinal germ-cell cancer. This syndrome was found only in patients with nonseminomatous mediastinal germ-cell tumors, particularly those with serologic or histologic evidence of yolk-sac elements. The two most common hematologic neoplasms seen in this syndrome were acute megakaryoblastic leukemia and malignant histiocytosis. Consistent cytogenetic abnormalities have not yet been identified, but the finding of the marker chromosome isochromosome (12p) in the mediastinal germ-cell tumor and associated leukemic blasts in one patient suggests that these tumors may arise from a common progenitor cell.
Topics: Adolescent; Adult; Bone Marrow Diseases; Child; Chromosomes, Human, Pair 12; Hematologic Diseases; Histiocytic Sarcoma; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Mediastinal Neoplasms; Middle Aged; Neoplasms, Germ Cell and Embryonal; Neoplasms, Multiple Primary; Syndrome
PubMed: 2158625
DOI: 10.1056/NEJM199005173222004 -
The Medical Journal of Malaysia Dec 2001A fulminant clinical presentation with high fever and hepatosplenomegaly, together with a course of worsening pancytopenia, coagulopathy and liver failure, is suggestive...
A fulminant clinical presentation with high fever and hepatosplenomegaly, together with a course of worsening pancytopenia, coagulopathy and liver failure, is suggestive of the haem syndrome (HPS). Bone marrow examination is diagnostic. We present 3 cases of HPS associated with different aetiologies including acute Ebstein Barr virus infection, T cell lymphoma, and malignant histiocytosis. In all the cases, the diagnosis was made late and the patients succumbed before definitive therapy could be administered.
Topics: Adult; Fatal Outcome; Histiocytosis, Non-Langerhans-Cell; Humans; Male; Middle Aged
PubMed: 12014773
DOI: No ID Found -
Journal of Equine Science 2009Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be... (Review)
Review
Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia.
PubMed: 24833969
DOI: 10.1294/jes.20.59 -
British Journal of Haematology Dec 1997Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly,... (Review)
Review
Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1beta, IL-2 or tumour necrosis factor-alpha. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.
Topics: Aged; Cytokines; Female; Herpesviridae; Herpesvirus 4, Human; Histiocytic Sarcoma; Human T-lymphotropic virus 1; Humans; Immunophenotyping; Lymphoma, B-Cell; Middle Aged; Vascular Neoplasms
PubMed: 9401080
DOI: 10.1046/j.1365-2141.1997.4623265.x -
Archives of Pathology & Laboratory... Nov 2018Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In... (Review)
Review
CONTEXT.—
Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform. Histiocytic sarcomatous transformation is rare and portends poor prognosis.
OBJECTIVE.—
To review the clinical features, morphology, and key points related to the differential diagnosis for histiocytic sarcoma. We discuss recent understanding of the biology underlying transformation.
DATA SOURCES.—
University of Michigan case and review of pertinent literature about histiocytic sarcoma and morphologic differential diagnosis.
CONCLUSIONS.—
Histiocytic sarcoma is a rare histiocytic neoplasm that can arise as a result of transdifferentiation from low-grade B-cell lymphomas, and has a wide differential diagnosis including other histiocytic/dendritic cell neoplasms, myeloid neoplasms, lymphomas, melanoma, and carcinoma. However, some key morphologic and immunohistochemical features allow for accurate classification.
Topics: Cell Transformation, Neoplastic; Diagnosis, Differential; Histiocytic Sarcoma; Humans; Lymphoma, B-Cell
PubMed: 30407858
DOI: 10.5858/arpa.2018-0220-RA -
International Journal of Surgery Case... Aug 2022Ewing sarcomas are a group of small round cell tumors that occur predominantly in the long bones as well as in extraosseous locations such as the extremities, trunk, and...
INTRODUCTION AND IMPORTANCE
Ewing sarcomas are a group of small round cell tumors that occur predominantly in the long bones as well as in extraosseous locations such as the extremities, trunk, and retroperitoneum (Gier, 1997) [2]. Extraosseous Ewing sarcoma (EES) is a type of small round cell tumor that occurs in soft tissues. I rare cases, EES occurs in the esophagus (Maesawa et al., 2002; Johnson et al., 2010) [1,3]. Ewing's sarcoma is a rare and highly aggressive cancer most frequently arising in people under 20 years of age. We report an uncommon case of primary paraesophageal Ewing's sarcoma in a 25-year-old female.
CASE PRESENTATION
A 26 years old Asian female referred primarily for surgical treatment due to esophageal cancer detected on her diagnostic investigations and revealed a primary tumor located near the gastroesophageal junction. Based on the results of diagnostic investigations which confirmed the possibility of the tumor Ewing sarcoma of esophagus, which was biopsy and immune histochemical stain proven the patient was qualified for surgical treatment. She underwent Mckewon esophagectomy on October 2021 for Ewing sarcoma of esophagus. She was first followed with neoadjuvant intravenous chemotherapy, after taking three cycles of neoadjuvant chemo showed good response in CT scan the patient underwent Mckewon esophagectomy, post op recovery was smooth she underwent 2 cycles of adjuvant chemotherapy after four months of surgery. Her followup visit was uneventful.
CLINICAL DISCUSSION
Ewing's sarcoma is the second most frequent primary malignant bone cancer, after osteosarcoma. It was first described by James Ewing in 1921, as an undifferentiated tumor developing in the diaphysis of the ulna of a young female patient (Ushigome et al., 2002) [6]. Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), previously thought to be separate tumors, is now treated as the same tumor; both have similar immunohistochemical characteristics and chromosomal translocation (Maesawa et al., 2002) [1]. They are malignant tumors composed of undifferentiated small round cells, usually affecting children, adolescents, and young adults (Kondo et al., 2005) [7]. Generally ES/PNET affects the bones and deep soft tissues (Soulard et al., 2005) [8], although other organs such as the pancreas, small bowel, esophagus, kidneys, prostate, ovaries, vagina and rectovaginal septum have been reported; this is termed as extraskeletal ES/PNET (Bloom et al., 1995) [9]. To the best of our knowledge, only 5 cases of gastric ES/PNET have been reported in the English language literature. Extraskeletal Ewing's sarcoma is a very rare disease, accounting for 6 %-47 % of all cases of Ewing's sarcoma. It is mainly diagnosed in the trunk, extremities, retroperitoneum, and head and neck region. Patients with extraosseous Ewing's sarcoma are more likely to be older, female, and not of Caucasian origin. An extraskeletal origin of the disease is correlated to poor prognosis (Siegel et al., 1988; Granowetter and West, 1997; Ushigome et al., 2002) [4-6]. We present an uncommon case of extraskeletal Ewing's sarcoma, and discuss its rare presentation and evolution. To our knowledge, this is the first reported case of paraesophageal primary Ewing's sarcoma and primitive neuroectodermal tumor. Adenocarcinoma and squamous cell carcinoma account for the vast majority of esophageal malignancies. Other malignancies known to occur in the esophagus include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is the commonest with both carcinomatous and sarcomatous elements followed by leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma, granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and epithelioid sarcoma.
CONCLUSION
Ewing sarcoma is a rare entity among all esophageal malignancies. It presents as an exophytic mass, and in this case, it has presented as a mass occluding the lumen of esophagus. Most of these tumors present in locally advanced and disseminated condition, one of the reasons being difficulty and hence delay in diagnosis. In spite of best efforts, a group among them remains to be histologically uncharacterized.
PubMed: 35926382
DOI: 10.1016/j.ijscr.2022.107399 -
Open Access Macedonian Journal of... Jan 2018Histiocytic sarcoma (HS) is an extremely rare, non-Langerhans cell tumor. HS affects especially adults, its etiology is unknown yet. Skin could be interested by papules...
BACKGROUND
Histiocytic sarcoma (HS) is an extremely rare, non-Langerhans cell tumor. HS affects especially adults, its etiology is unknown yet. Skin could be interested by papules or nodules, single or multiple.
CASE REPORT
A Caucasian man in his late 40s came to our clinic for a naevi evaluation. During the visit, a rose papulonodular lesion was observed in the lumbar region. This lesion was completely asymptomatic, and it had been there for an indefinite period. The clinical evaluation revealed that the lesion appeared elevated, of 9 x 15 mm in dimension, symmetrical and of a homogeneous pinkish colour. The videodermoscopical evaluation revealed a homogeneous yellow central pattern, polymorphic vessels, an eccentric peripheral pigmentation and a white collar. An excisional biopsy was performed. The morphology and the expression of CD163, CD68 and/or lysozyme to the immunophenotypic analysis, revealed the true nature of the lesion.
CONCLUSION
HS is usually diagnosed at an already advanced clinical stage and it has a high mortality rate even today. Dermoscopy, showing a yellow and distributed homogeneously colour, can facilitate its hard diagnosis.
PubMed: 29483989
DOI: 10.3889/oamjms.2018.039