Malignant Histiocytosis Research Articles

Cerebrospinal fluid from a 10‐year‐old dog with a single seizure episode

A cerebrospinal fluid sample collected from the cerebellomedullary cistern of a 10-year-old Shetland Sheepdog with a recent history of seizures was submitted for fluid analysis and cytologic examination. Key findings included a total nucleated cell count of 520/microL (reference interval 0-5 cells/microL), with a predominance of mononuclear cells, a protein concentration of 51.8 mg/dL (reference interval 0-35 mg/dL), and a glucose concentration of 44.7 mg/dL (reference interval 52-105 mg/dL). There was marked atypia of the mononuclear cells, with abundant eosinophilic cytoplasm, marked anisocytosis and anisokaryosis, occasional binucleated cells, mitotic figures, and rare erythrophagia. The cytologic interpretation was marked, monocytoid-rich, mixed cell pleocytosis with cellular atypia worrisome for neoplasia. In addition to histiocytic neoplasia, differentials included granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and granulomatous inflammation. The dog did not respond to anti-inflammatory and anticonvulsive therapy. At necropsy, a mass involving the meninges and subtending the neuropil of the right temporal lobe of the cerebrum was found. Histologically, the mass was composed of large, bizarre histiocytic cells with multinucleated forms and numerous mitotic figures. Using immunochemistry on cytologic and histologic samples, the pleomorphic histiocytic cells were positive for CD1c, CD11ad, CD45, lysozyme, and vimentin, and were negative for CD3, CD4, CD79a, CD90, and pancytokeratin. These findings supported a diagnosis of primary CNS malignant histiocytosis of dendritic antigen-presenting cell (CD1c+) origin. To our knowledge, this is only the third reported case of primary CNS histiocytic sarcoma in dogs, and the first to demonstrate strong immunochemical evidence for dendritic antigen-presenting cell origin.

Malignant Histiocytosis of the Brain in Three Dogs

Three dogs (two Rottweilers and a Flat-coated retriever) showed various neurological signs, including apathy, depression, circling, a partial decrease in functions associated with cranial nerves, seizures, hyperaesthesia, proprioceptive deficits, and increased spinal reflexes. In all three cases, necropsy revealed a solid, distinct, white mass in the brain and multiple, poorly demarcated, firm nodular proliferations in the lung; in one case the liver was also affected. Histopathological examination showed loosely aggregated, pleomorphic cells, with abundant eosinophilic cytoplasm. The neoplastic cells sometimes contained vacuoles or phagocytized cells. Binucleated and multinucleated giant cells, and mitotic figures, were common. Immunohistochemically, the tumour cells reacted strongly for lysozyme and vimentin, but there was no reaction for S-100 protein, cytokeratin, CD3 or CD79a. The histological and immunohistochemical examinations indicated a histiocytic origin of the tumour cells and malignant histiocytosis was therefore diagnosed.

Efficacy of Carboplatin and Radiation on Malignant Histiocytosis in a Bernese Mountain Dog

左肘部の腫瘤を主訴に6歳齢、雄のバーニーズマウンテンドッグが来院し、悪性組織球症と診断された。腫瘤と所属リンパ節を外科的に切除したが、術後3日で術野に再発が見られたため、放射線療法（常電圧装置、40日間に計36 Gy）とカルボプラチン（300 mg/m2、6カ月間に9回投与）の投与を実施したところ、6カ月後には腫瘤は完全に寛解した。約450日間にわたって寛解が持続した後、局所再発や肺転移が認められた。治療の難しいバーニーズマウンテンドッグの悪性組織球症に対して外科的摘出と補助的なカルボプラチン投与、放射線療法の併用は有効な治療法の一つとなり得る可能性が示唆された。

A Retrospective Study of the Incidence and the Classification of Bone Marrow Disorders in the Dog at a Veterinary Teaching Hospital (1996–2004)

An 8-year retrospective study was conducted to evaluate the prevalence and the classification of canine bone marrow disorders in a clinical pathology service at a university referral hospital. Dogs evaluated for bone marrow disorders at a veterinary teaching hospital. A better understanding of the spectrum and the prevalence of canine bone marrow disorders can be achieved with a multiyear retrospective study. Bone marrow aspirate smears, core biopsy specimens, and case records from 717 dogs were reviewed. Bone marrow specimens were first categorized based on the presence or the absence of a primary bone marrow disorder. Nondysplastic and nonmalignant pathologic changes were placed into 14 subcategories. Frequently observed pathologic disorders included nonregenerative immune-mediated anemia, pure red cell aplasia, bone marrow necrosis, myelofibrosis, and hemophagocytic syndrome. Dysmyelopoiesis (n = 61) was subcategorized into myelodysplastic syndromes (n = 27), and congenital (n = 1) and secondary (n = 33) dysmyelopoiesis. One hundred twenty-six cases of neoplasia were divided into acute leukemia (n = 46), chronic leukemia (n = 7), stage 5 malignant lymphoma (n = 28), multiple myeloma (n = 25), malignant histiocytosis (n = 11), metastatic mast-cell tumor (n = 3), sarcoma (n = 5), and carcinoma (n = 1). This study provides a general indication of the spectrum and the prevalence of canine bone marrow disorders at a referral center in North America.

Some Unusual Indications Of Splenectomy

While dealing with various hematological disorders which were subjected to therapeutic splenectomy in our department of general surgery at a tertiary care centre Sher-i-Kashmir Institute of Medical Sciences over a period of more than 20 years, we came across a rare group of diseases in our set up from time to time. This rare group included 5 patients with 1. Hairy cell leukemia -1, 2 Malignant histiocytoma -1, 3 Gaucher's disease -1, 4 Tropical splenomegaly -1, and 5 Splenic hemianginoma-1. All these patients were referred to our department from the department of clinical hematology of the same institute for splenectomy for various types of cytopenias. Response to splenectomy was excellent in malignant histiocytosis, splenic hemiangioma and some of the parameters in hairy cell leukemia and Gaucher's disease, while as an unsatisfactory response was observed in tropical splenomegaly sydrome and in some of the parameters of hairy cell leukemia and Gaucher's disease.

Unusual histiocytic disease in a Somali cat

An 8-year-old Somali cat presented with a 9-month history of inappetence, vomiting and weight loss. The disease progressed to involve neurological signs associated with a mass lesion at the level of the first lumbar vertebra. Histopathology identified the condition as malignant histiocytosis affecting the lungs, stomach, mesenteric lymph nodes, liver, spleen, brain and spinal cord. However, the presentation of this case differs from previously reported cases of malignant histiocytosis, and may therefore represent a variant form of histiocytic disease.

Flow cytometric analysis of effusions in dogs and cats with the automated haematologyanalyser ADVIA 120

Samples were aspirated from 12 thoracic effusions, 10 abdominal effusions and four pericardial effusions in 17 dogs and nine cats. They were analysed cytometrically with the ADVIA 120 flow cytometer...

Magnetic resonance imaging characterization of canine splenic lesions

Introduction: Splenic lesions are a common finding in veterinary medicine and typically 1/2 to 2/3 of these lesions are malignant. Due to the limited accuracy of ultrasound, unnecessary exploratory surgeries/biopsies may be performed for benign lesions and treatment may be delayed for malignant ones. Splenic lesions are rare in people. MR imaging, with its inherently high soft tissue contrast, is efficacious in imaging the human spleen. We have previously demonstrated the efficacy of MRI to differentiate canine hepatic lesions. In that study 8 splenic lesions were all accurately characterized. This current study represents a further evaluation of splenic lesions.Methods: In this prospective study, 27 dogs with splenic lesions were accrued. Histopathological/cytological confirmation of lesions occurred either before or shortly after imaging. MRI clinicians were blinded to histopathology results. MR (General Electric, 1.5 Tesla) images using a variety of sequences were obtained before and after intravenous administration of gadolinium.Results: 32 lesions (9 malignant, 23 benign) were evaluated in 27 dogs. Lesions were confirmed via histopathology (n = 20) or cytology (n = 12). Benign lesions included, EMH (n = 7), hematoma/hemorrhage (n = 5), lymphoid hyperplasia (n = 9), and hemangioma (n = 2). Malignant lesions included anaplastic sarcoma (n = 3), malignant histiocytosis (n = 2), hemangiosarcoma (n = 2), plasma cell tumor (n = 1) and adenocarcinoma (n = 1). The overall accuracy in differentiating benign from malignant lesions was 88%(29/32 lesions). The overall sensitivity and specificity were 100%(95% CI, 66–100) and 87%(95% CI 66–97).Conclusions: Based upon these results, MRI is both sensitive and specific in distinguishing between malignant and benign splenic lesions.

Fulminant Multisystem Non–Langerhans Cell Histiocytic Proliferation With Hemophagocytosis

Abstract Hemophagocytosis (HP), a feature seen in malignant histiocytosis and infection- and lymphoma-associated disorders, has not been previously emphasized in Erdheim-Chester disease (ECD). Generally, ECD is recognized as a rare, systemic, non–Langerhans cell histiocytosis with a variable clinical course. Herein, we describe a unique case of multisystem non–Langerhans cell histiocytic proliferation with a fulminant clinical course (death occurred within 3 months of presentation) that showed prominent HP and extensive involvement of multiple organs, including the lungs, resulting in respiratory failure. Hemophagocytosis led to severe anemia that required transfusion and thrombocytopenia. Antemortem lung and bone marrow biopsy specimens revealed involvement by a histiocytic infiltrate with features highly suggestive of ECD and HP. Furthermore, the autopsy documented the presence of HP and the histiocytic infiltrate in multiple other organs. This case is best categorized as a variant form of ECD. Recognizing this variant has the following important implications: (1) HP may be a marker for fulminant clinical course in ECD, (2) the presence of HP does not exclude a diagnosis of ECD, and (3) ECD should be considered in the differential diagnosis of HP.

Fulminant Multisystem Non-Langerhans Cell Histiocytic Proliferation With Hemophagocytosis A Variant Form of Erdheim-Chester Disease

c Hemophagocytosis (HP), a feature seen in malignant histiocytosis and infection- and lymphoma-associated disorders, has not been previously emphasized in Erdheim-Chester disease (ECD). Generally, ECD is recognized as a rare, systemic, non‐Langerhans cell histiocytosis with a variable clinical course. Herein, we describe a unique case of multisystem non‐Langerhans cell histiocytic proliferation with a fulminant clinical course (death occurred within 3 months of presentation) that showed prominent HP and extensive involvement of multiple organs, including the lungs, resulting in respiratory failure. Hemophagocytosis led to severe anemia that required transfusion and thrombocytopenia. Antemortem lung and bone marrow biopsy specimens revealed involvement by a histiocytic infiltrate with features highly suggestive of ECD and HP. Furthermore, the autopsy documented the presence of HP and the histiocytic infiltrate in multiple other organs. This case is best categorized as a variant form of ECD. Recognizing this variant has the following important implications: (1) HP may be a marker for fulminant clinical course in ECD, (2) the presence of HP does not exclude a diagnosis of ECD, and (3) ECD should be considered in the differential diagnosis of HP. (Arch Pathol Lab Med. 2005;129:e39‐e43)

Ought to recognize malignant histocytosis with new view-point

世界卫生组织(WHO)在1999年提出的淋巴组织与造血组织肿瘤分类中恶性组织细胞病(malignant histiocytosis, MH)的病名已经消失[1],因为通过有关的近代实验技术已确认MH的实质为间变性大细胞性淋巴瘤(anaplastic large cell lymphoma, ALCL)或噬血细胞淋巴组织细胞增生症(hemophagocytic lympho histiocytosis, HLH)。

Growth Characteristics of Canine Distemper Virus in a New Cell Line CCT Cells Originated from Canine Malignant Histiocytosis

Canine distemper virus (CDV) growth and the morphological characterization were examined in a cell line established from a canine malignant histiocytosis (CCT cell line). The susceptibility of the CCT cells to 3 CDV strains, FXNO, YSA-TC and MD-77 was shown by detection of the antigen in the indirect fluorescent assay. After passaging 4 and 9 times through the CCT cells, only FXNO strain could produce the syncytia where demonstrated the antigens. Titers of 9 passaged viruses through the CCT cells showed slightly higher in the CCT cells than those in Vero cells. Morphological characterization of karyorrhexis and specific DNA ladder by extracted DNA electrophoresis indicated apoptosis in the CDV infected CCT cells.

Enfermedad de Erdheim-Chester e histiocitosis de células de Langerhans: ¿Una asociación fortuita?

Erdheim-Chester disease is an idiopathic systemic histiocytosis hystologically different to Langerhans histiocytosis which is characterized by symmetric sclerotic bone lesions, predominantly affecting the diaphyseal and metaphyseal areas of large bones. It is not classified within malignant histiocytosis, but the clinical course tends to be aggressive with a poor response to different schedules of treatment. In rare cases the association of both entities has been reported: Erdheim-Chester disease and Langerhans histiocytosis. We present a new case with histological data of both histiocytosis whose clinical course included bone and muscle pain, insipidus diabetes, exophthalmos, bilateral symmetrical sclerosing bone lesions and a cerebellar syndrome.

SONOGRAPHIC FEATURES OF HISTIOCYTIC NEOPLASMS IN THE CANINE ABDOMEN

The purpose of this retrospective study was to describe the ultrasonographic features of malignant histiocytosis (MH), malignant fibrous histiocytoma, and histiocytic sarcoma in abdominal organs of dogs. The medical records of 18 dogs that had undergone abdominal sonography and had a histopathologic diagnosis of abdominal MH, malignant fibrous histiocytoma, and histiocytic sarcoma were reviewed. The organ most commonly affected was the spleen. MH was the most common followed by histiocytic sarcoma and malignant fibrous histiocytoma. In the spleen there were often multiple hypoechoic nodules with well-defined borders. In one dog, without focal lesions, the spleen was enlarged and hypoechoic. The liver was the second most commonly affected organ. MH was most common followed by histiocytic sarcomas and malignant fibrous histiocytoma. The most common sonographic feature in the liver was the presence of multiple hypoechoic nodules with well-defined borders. One dog without hepatic nodules had a liver that was ultrasonographically enlarged and hypoechoic. MH in the abdominal lymph nodes resulted in hypoechoic lymphadenopathy. Malignant fibrous histiocytoma was the only neoplastic type in the kidneys appearing as a single heteroechoic renal mass with well-defined borders. MH was observed in the stomach of one dog. Sonographically there was a single well circumscribed hypoechoic mass with well-defined borders and abnormal stomach layers. In this study it was not possible to differentiate between MH, malignant fibrous histiocytoma, and histiocytic sarcoma using sonography.

Second malignant neoplasms (SMN) in childhood acute lymphoblastic leukemia (ALL): Primitive neuroectodermal tumor of bone (PNET) with p53 mutation

8173 Background: About 80% of children treated for ALL will be long term survivors. The estimated cumulative risk of a SMN is 2% to 3.3% 15 yrs after diagnosis. Methods: A review of the literature of 25,907 children treated for ALL revealed 274 SMN (1.07%). Results: The most frequently observed SMN are shown below: Others included CML(3), breast cancer (4), malignant histiocytosis (2), ovarian cancer (2), one case each of nephroblastoma, mucoepidermoid CA, bladder CA, malignant teratoma, leimyosarcoma of lung, and 22 unknown cases. In the lymphoma group there was an equal number of NHL and Hodgkins (10). In the AML/MDS group most were AML(26). Of all cases of SMN 62% recieved RT and the risk of a SMN appears to be dose related. Of significance is the fact that the overall survival rate for those patients with reported long term follow is 57.3% (101/176). The Ewings Family tumors and in particular PNET of bone are rare SMN. Of these 25,901 children treated for ALL there is only one case report of a PNET of bone. Our case of a chest wall PNET developing in an 8-yr-old boy one yr after completing therapy for standard risk ALL is the second case reported and the first one associated with germline and tumor cell p53 mutation. . Our patient did not receive RT and therefore can be excluded as a contributing factor. Exposure to anthracyclines and alkylating agents was minimal (75mg/m2 and 1gm/m2 of adriamycin and cytoxan respectively). Conclusions: We conclude that germline p53 mutation played a major role in the development of this rarely observed SMN and that cases of SMN in pediatric patients should be evaluated for p53 mutation. Overall long term survival for patients with SMN after treatment for ALL is encouraging at 57% and determination of p53 may influence therapeutic and prognostic considerations. One percent of children treated for ALL will develop SMN, the decrease use of RT in children with ALL should result in even a lower number of SMN. No significant financial relationships to disclose.

Second malignant neoplasms (SMN) in childhood acute lymphoblastic leukemia (ALL): Primitive neuroectodermal tumor of bone (PNET) with p53 mutation

8173 Background: About 80% of children treated for ALL will be long term survivors. The estimated cumulative risk of a SMN is 2% to 3.3% 15 yrs after diagnosis. Methods: A review of the literature of 25,907 children treated for ALL revealed 274 SMN (1.07%). Results: The most frequently observed SMN are shown below: Others included CML(3), breast cancer (4), malignant histiocytosis (2), ovarian cancer (2), one case each of nephroblastoma, mucoepidermoid CA, bladder CA, malignant teratoma, leimyosarcoma of lung, and 22 unknown cases. In the lymphoma group there was an equal number of NHL and Hodgkins (10). In the AML/MDS group most were AML(26). Of all cases of SMN 62% recieved RT and the risk of a SMN appears to be dose related. Of significance is the fact that the overall survival rate for those patients with reported long term follow is 57.3% (101/176). The Ewings Family tumors and in particular PNET of bone are rare SMN. Of these 25,901 children treated for ALL there is only one case report of a PNET of bone. Our case of a chest wall PNET developing in an 8-yr-old boy one yr after completing therapy for standard risk ALL is the second case reported and the first one associated with germline and tumor cell p53 mutation. . Our patient did not receive RT and therefore can be excluded as a contributing factor. Exposure to anthracyclines and alkylating agents was minimal (75mg/m2 and 1gm/m2 of adriamycin and cytoxan respectively). Conclusions: We conclude that germline p53 mutation played a major role in the development of this rarely observed SMN and that cases of SMN in pediatric patients should be evaluated for p53 mutation. Overall long term survival for patients with SMN after treatment for ALL is encouraging at 57% and determination of p53 may influence therapeutic and prognostic considerations. One percent of children treated for ALL will develop SMN, the decrease use of RT in children with ALL should result in even a lower number of SMN. No significant financial relationships to disclose.

Histiocytic sarcoma with fatal duodenal ulcers

Histiocytic sarcoma is an uncommon neoplasm of mature histiocytes with very poor outcome. We report an autopsy case of a true histiocytic sarcoma with characteristic symptoms of so-called “malignant histiocytosis of the intestine”. The liver and spleen were enlarged, with remarkable tumor cell infiltration in the hepatic sinusoids and splenic sinuses. Tumor cells aggregated to form sporadic nodular lesions in the liver, which often showed coagulative necrosis. Infarcted lesions also occurred at the splenic subcapsular area. In addition, tumor cell infiltration was noted in the sinuses of bone marrow and lymph node. Tumor cells often demonstrated moderate pleomorphism with multinucleated giant cells. They were positive for CD68 and negative for T- and B-cell lineage markers, megakaryocytic markers, and CD30. Various examinations were done to rule out infection-associated hemophagocytic syndrome, and the absence of infectious diseases was revealed. Thus, the diagnosis of histiocytic sarcoma was made. Apart from these lesions, multiple ulcerations, some with fatal perforation, were found in the esophagus and duodenum. They showed only non-specific inflammatory changes without tumor cell involvement. The ulcers probably derived from ischemic condition through an embolic process caused by tumor cell infiltration elsewhere in the blood vessels at the periphery of the ulcers.

Efficacy and toxicity of paclitaxel (Taxol) for the treatment of canine malignant tumors.

Paclitaxel (Taxol) was administered to 25 dogs with histologically confirmed malignant tumors at a dosage of 165 mg/m2 i.v. over 3-6 hours every 3 weeks. Dogs received premedication with antihistimines and corticosteroids to reduce hypersensitivity reactions. However, 64% of the dogs still experienced allergic reactions. Six dogs (24%) had grade 3 or 4 neutropenia, 6 dogs (24%) required hospitalization and 3 dogs (12%) died of sepsis. Five dogs (20%) had a partial response (osteosarcoma [2 dogs] mammary carcinoma [2 dogs] and malignant histiocytosis [1 dog]) for a median duration of 53 days. The overall toxicity was unacceptable at the 165 mg/m2 dose. Therefore, subsequent evaluations of paclitaxel in tumor-bearing dogs should a starting dose of 132 mg/m2 i.v. every 3 weeks.

MALIGNANT FIBROUS HISTIOCYTOMA (INFLAMMATORY VARIANT) IN A CHILD PRESENTING AS PARAPARESIS

Malignant fibrous histiocytoma (MFH) in the pediatric age group is extremely rare. Inflammatory variant of MFH is still rarer in children, to the extent that only few case reports of inflammatory variant of MFH are available in the English literature. This report is of a case in a 4-year-old male child, who presented with a chest wall swelling. Fine needle aspiration (FNA) smears showed neutrophilic infiltrate was seen in and around the tumor cells showing a prominent neutrophillic phagocytosis. Possibilities of malignant fibrous histiocytoma, malignant rhabdoid tumor and malignant histiocytosis were offered on cytology. Subsequently, an excision biopsy was performed and was diagnosed as inflammatory variant of MFH. Differential diagnosis of this type of tumor with prominent neutrophillic phagocytosis is discussed with importance of immunostaining for diagnosis. Paraparesis as a presenting feature of inflammatory MFH is rare in children and has not been reported in the literature to the best of our knowledge.

Epithelial membrane antigen (EMA) or MUC1 expression in monocytes and monoblasts

Epithelial membrane antigen (EMA) or MUC1 belongs to a heterogeneous group of heavily glycosylated proteins and is expressed in most normal and epithelial neoplastic cells. EMA is also expressed in plasma cells, anaplastic large cell lymphoma (Ki-1 antigen), malignant histiocytosis and erythroleukaemia. In 1996, Cheong et al. (Hematology 1996; 1: 223) demonstrated the positive expression of EMA in monoblasts. Since there were very few useful markers for differentiating subtypes of acute myeloid leukaemia with a monocytic component from the those without, a study was conducted to evaluate the prevalence of EMA expression and its relationship with known markers for monocytic-macrophage lineage (CD11c, CD14 and intracellular CD68) in monocytes and monoblasts. EMA detection was performed by flow cytometry in monocytes and monoblasts. EMA expression was compared with other known markers of monocytic-macrophage lineage (CD11c, CD14 and intracellular CD68). Samples of purified monocytes were obtained from 20 healthy volunteers. Twenty-two cases of monocytic AML (M4 and M5) were studied and controls were selected from 20 cases of acute lymphoblastic leukaemia (ALL) and 18 cases of non-monocytic AML (M0, M1, M2, M3, and M7). EMA was shown to be expressed strongly on the surface of all purified monocytes. EMA expression was observed on blast cells in 18/22 (81.8%) cases of AML M4 and M5, but not in that of non-monocytic AML or ALL. In this study EMA monoclonal antibody has demonstrated a strong association (P<0.001) with all the other known markers of monocytic-macrophage lineage in acute leukaemia subtypes. EMA had also shown 100% specificity and 81.8% sensitivity in the diagnosis of AML M4 and M5. The monoclonal antibody EMA (clone E29) is a useful marker in the classification of acute myeloid leukaemia and can be used as a supplementary analysis for the diagnosis of acute leukemia with monocytic involvement.