Carcinocythemia

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Carcinocythemia
Other namesCarcinoma cell leukemia
Carcinocythemia - malignant tumour cells in peripheral blood (cropped v1).png
A case of carcinocythemia. The large, round cells are breast cancer cells circulating in the peripheral blood. [1]
Specialty Hematology, oncology
CausesUsually secondary to metastatic cancer in the bone marrow
Differential diagnosis Acute leukemia, lymphoma, leukemoid reaction, circulating immature cells from chemotherapy, circulating endothelial cells, megakaryocytes or osteoclasts
PrognosisPoor; 15% survival rate at 6 months

Carcinocythemia, also known as carcinoma cell leukemia, [2] is a condition in which cells from malignant tumours of non-hematopoietic origin are visible on the peripheral blood smear. [3] [4] It is an extremely rare condition, [5] with 33 cases identified in the literature from 1960 to 2018. [4] Carcinocythemia typically occurs secondary to infiltration of the bone marrow by metastatic cancer [6] and carries a very poor prognosis. [3] [4] [5]

Haematopoiesis the formation of blood cellular components

Haematopoiesis (, from Greek αἷμα, "blood" and ποιεῖν "to make"; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.

Bone marrow is a semi-solid tissue which may be found within the spongy or cancellous portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production or hematopoiesis. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg will have around 3.65 kg of bone marrow.

Contents

Presentation

Carcinocythemia occurs most commonly in breast cancer, followed by small cell lung cancer, and usually appears late in the course of the disease. [4] Thrombosis and disseminated intravascular coagulation are frequently reported in association with carcinocythemia. [2] [4] The prognosis is poor: a review of 26 patients found that 85% died within 6 months of the diagnosis, with an average time of 6.1 weeks between diagnosis and death. [4]

Breast cancer cancer that originates in the mammary gland

Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly-inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

Thrombosis vascular disease caused by the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

Disseminated intravascular coagulation pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include blood in the urine, blood in the stool, or bleeding into the skin. Complications may include organ failure.

The amount of tumour cells on the blood smear can range from 1 to 80 percent of the total white blood cell count, [4] with lower percentages being more common. [3] Carcinocythemia is distinct from the presence of circulating tumour cells (CTCs), as CTCs usually occur in such low quantities that they cannot be seen on blood smear examination, requiring special techniques for detection. [2] [7]

Mechanism

The mechanism of carcinocythemia is poorly understood. Some patients with carcinocythemia show evidence of impaired spleen function, and it has been suggested that dysfunction of the reticuloendothelial system, preventing phagocytosis of malignant cells, could contribute to the presence of tumour cells in the blood. [4] [8]

The term “the reticuloendothelial system”, often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that effectively clear colloidal vital stains from the blood circulation. The term is still used today, but its meaning has changed over the years, and is used inconsistently in present-day literature. Although RES is commonly associated exclusively with macrophages, recent research has revealed that the cells that accumulate intravenously administrated vital stain belong to a highly specialised group of cells called scavenger endothelial cells (SECs), that are not macrophages..

Phagocytosis An endocytosis process that results in the engulfment of external particulate material by phagocytes. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the par

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis pinocytosis.

Diagnosis

Carcinocythemia can be detected on a routine blood smear examination or manual differential. [8] If the number of suspicious cells is low, a smear can be prepared from the buffy coat of the blood sample to concentrate the cells. [3]

Buffy coat component of blood

The buffy coat is the fraction of an anticoagulated blood sample that contains most of the white blood cells and platelets following density gradient centrifugation of the blood.

Tumour cells in peripheral blood may look similar to circulating blasts or lymphoma cells. [3] [9] Features that aid in distinguishing tumour cells from other cells include their very large size, mature nuclear chromatin pattern, vacuolated cytoplasm, and their tendency to appear in clumps or clusters, although some of these characteristics are shared by megakaryoblasts and monoblasts. Tumour cells are often found at the edge of the blood smear due to their large size, so this area should be examined thoroughly if carcinocythemia is suspected. [4]

Lymphoma hematologic cancer that affects lymphocytes that reside in the lymphatic system and in blood-forming organs

Lymphoma is a group of blood cancers that develop from lymphocytes. The name often refers to just the cancerous versions rather than all such tumors. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

Chromatin is a complex of DNA and protein found in eukaryotic cells. Its primary function is packaging very long DNA molecules into a more compact, denser shape, which prevents the strands from becoming tangled and plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed networks of chromatin.

Cytoplasm all of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures

In cell biology, the cytoplasm is all of the material within a cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main components of the cytoplasm are cytosol – a gel-like substance, the organelles – the cell's internal sub-structures, and various cytoplasmic inclusions. The cytoplasm is about 80% water and usually colorless.

Cytochemical staining and immunohistochemistry techniques can help determine the lineage of the cells. [4] When immunophenotyped by flow cytometry, the cells are generally CD45 negative and may express CD56, a profile that is non-specific but unusual for hematologic malignancies. [3] In some cases, flow cytometry and FISH results may be misleading, as circulating tumour cells can exhibit cell markers and chromosomal abnormalities associated with hematologic diseases. [4]

Bone marrow examination is indicated in carcinocythemia to better characterize the tumour cells. [3] [4]

Differential diagnosis

Carcinocythemia must be distinguished from the following conditions: [3] [4] [8]

History

The presence of tumour cells in the peripheral blood of a cancer patient was first described in an 1869 case report in the Medical Journal of Australia . [8] [10] The term carcinocythemia was first used in 1976 by Robert Carey. [8] [11] In 1984, a review of 10 cases was published, noting the condition's poor prognosis. [12]

Other animals

As of 2018, there were two documented cases of carcinocythemia in dogs and one case in a cat. [13]

Related Research Articles

Adenocarcinoma carcinoma that has material basis in abnormally proliferating cells, derives from epithelial cells, which originate in glandular tissue

Adenocarcinoma is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.

Carcinoma A category of types of cancer that develops from epithelial cells

Carcinoma is a category of types of cancer that develop from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.

Burkitts lymphoma mature B-cell neoplasm of B-cells found in the germinal center

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. The overall cure rate for Burkitt's lymphoma in developed countries is about 90%, but worse in low-income countries. Burkitt's lymphoma is uncommon in adults, where it has a worse prognosis.

Chronic lymphocytic leukemia lymphoblastic leukemia characterized by over production of B-cells and their accumulation in bone marrow and blood

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes. Early on there is typically no symptoms. Later non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years.

Adult T-cell leukemia/lymphoma Human disease

Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1).

Desmoplastic small-round-cell tumor An aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.

Splenic marginal zone lymphoma (SMZL) is a type of cancer made up of B-cells that replace the normal architecture of the white pulp of the spleen. The neoplastic cells are both small lymphocytes and larger, transformed lymphoblasts, and they invade the mantle zone of splenic follicles and erode the marginal zone, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar lymph nodes are involved along with the peripheral blood. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.

Myelophthisic anemia is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue by fibrosis, tumors, or granulomas. The word comes from the roots myelo-, which refers to bone marrow, and phthysis, shrinkage or atrophy.

Acinic cell carcinoma carcinoma that has material basis in abnormally proliferating cells, derives from spindle cells and/or derives from giant cells

Acinic cell carcinoma is a malignant tumor representing 2% of all salivary tumors. 90% of the time found in the parotid gland, 10% intraorally on buccal mucosa or palate. The disease presents as a slow growing mass, associated with pain or tenderness in 50% of the cases. Often appears pseudoencapsulated.

Neprilysin protein-coding gene in the species Homo sapiens

Neprilysin, also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10), and common acute lymphoblastic leukemia antigen (CALLA) is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated as a cause of Alzheimer's disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface.

Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic elevation in large granular lymphocytes (LGLs) in the peripheral blood.

Aggressive NK-cell leukemia Human disease

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells and a rapidly declining clinical course.

Signet ring cell carcinoma adenocarcinoma that derives from epithelial cells originating in glandular tissue, which have signet ring appearance

Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.

A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments. Currently, there is one FDA-approved method for CTC detection, CellSearch, which is used to diagnose breast, colorectal and prostate cancer.

Oncology Branch of medicine dealing with cancer

Oncology is a branch of medicine that deals with the prevention, diagnosis, and treatment of cancer. A medical professional who practices oncology is an oncologist. The name's etymological origin is the Greek word ὄγκος (ónkos), meaning "tumor", "volume" or "mass" and the word λόγος (logos), meaning "study".

Renal medullary carcinoma

Renal medullary carcinoma is a rare type of cancer that affects the kidney. It tends to be aggressive, difficult to treat, and is often metastatic at the time of diagnosis. Most individuals with this type of cancer have sickle cell trait or rarely sickle cell disease, suggesting that the sickle cell trait may be a risk factor for this type of cancer.

Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).

Cancer biomarker

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

White blood cell differential Blood test for types and amounts of white blood cells

A white blood cell differential is a medical laboratory test that provides information about the types and amounts of white blood cells in a person's blood. The test, which is usually ordered as part of a complete blood count, measures the amounts of the five white blood cell types in normal human blood – neutrophils, lymphocytes, monocytes, eosinophils and basophils – as well as abnormal cell types if they are present. These results are reported as percentages and absolute values. Changes in the amounts of white blood cells can aid in the diagnosis of many health conditions, including viral, bacterial, and parasitic infections and blood disorders such as leukemia.

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