Carcinocythemia, also known as carcinoma cell leukemia, is a condition in which cells from malignant

tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

s of non-

hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

origin are visible on the

peripheral blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the i ...

. It is an extremely rare condition, with 33 cases identified in the literature from 1960 to 2018. Carcinocythemia typically occurs secondary to infiltration of the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

metastatic cancer Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

and carries a very poor prognosis.

Presentation

Carcinocythemia occurs most commonly in

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

, followed by

small cell lung cancer Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr ...

, and usually appears late in the course of the disease.

Thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...

and

disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...

are frequently reported in association with carcinocythemia. 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. The amount of tumour cells on the blood smear can range from 1 to 80 percent of the total white blood cell count, with lower percentages being more common. 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.

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 In anatomy the term reticuloendothelial system (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was employed by the beginning of the 20th century to denote a system of specialised cells that effectively cl ...

, preventing

phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

of malignant cells, could contribute to the presence of tumour cells in the blood.

Diagnosis

Carcinocythemia can be detected on a routine

blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the i ...

examination or manual differential. If the number of suspicious cells is low, a smear can be prepared from the

buffy coat The buffy coat is the fraction of an anticoagulated blood sample that contains most of the leukocytes and thrombocytes following centrifugation. Description After centrifugation, one can distinguish a layer of clear fluid (the plasma), a laye ...

of the blood sample to concentrate the cells. Tumour cells in peripheral blood may look similar to circulating blasts or

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

cells. Features that aid in distinguishing tumour cells from other cells include their very large size, mature nuclear chromatin pattern, vacuolated

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

, and their tendency to appear in clumps or clusters, although some of these characteristics are shared by

megakaryoblast A megakaryoblast () is a precursor cell to a promegakaryocyte. During thrombopoiesis, the promegakaryocyte matures into the form of a megakaryocyte. From the megakaryocyte, platelets are formed. The megakaryoblast is the beginning of the thromb ...

s and

monoblast Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. ...

s. 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. Cytochemical staining and

immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

techniques can help determine the lineage of the cells. When immunophenotyped by

flow cytometry Flow cytometry (FC) is a technique used to detect and measure the physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the ...

, the cells are generally

CD45 Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocy ...

negative and may express

CD56 Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...

, a profile that is non-specific but unusual for hematologic malignancies. In some cases, flow cytometry and

FISH A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

results may be misleading, as circulating tumour cells can exhibit

cell marker The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunopheno ...

s and chromosomal abnormalities associated with hematologic diseases.

Bone marrow examination Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditi ...

is indicated in carcinocythemia to better characterize the tumour cells.

Differential diagnosis

Carcinocythemia must be distinguished from the following conditions: *

Acute leukemia Acute leukemia or acute leukaemia is a family of serious medical conditions relating to an original diagnosis of leukemia. In most cases, these can be classified according to the lineage, myeloid or lymphoid, of the malignant cells that grow uncont ...

* Circulating immature cells secondary to

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

* Circulating

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

megakaryocyte A megakaryocyte () is a large bone marrow cell with a lobation, lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal blood coagulation, clotting. In humans, megakaryocytes usually account for 1 out of 10,00 ...

s or

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s *

Leukemoid reaction The term leukemoid reaction describes an increased white blood cell count (> 50,000 cells/μL), which is a physiological response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). It often describes the presence o ...

* Lymphoma

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 The ''Medical Journal of Australia'' (MJA) is a peer-reviewed medical journal published 22 times a year. It is the official journal of the Australian Medical Association, published by Wiley (publisher), Wiley on behalf of the Australasian Medical ...

''. The term ''carcinocythemia'' was first used in 1976 by Robert Carey. In 1984, a review of 10 cases was published, noting the condition's poor prognosis.

Other animals

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

References

{{reflist, 30em, refs= {{cite journal, last1=Ogura, first1=Kanako, last2=Amano, first2=Maki, last3=Matsumoto, first3=Toshiharu, last4=Sakaguchi, first4=Asumi, last5=Kosaka, first5=Taijiro, last6=Kitabatake, first6=Toshiaki, last7=Kojima, first7=Kuniaki, title=Occult Breast Lobular Carcinoma with Numerous Circulating Tumor Cells in Peripheral Blood, journal=Case Reports in Pathology, volume=2015, year=2015, pages=1–6, issn=2090-6781, doi=10.1155/2015/135684, pmid=26199779, pmc=4496473, doi-access=free {{cite book, author1=Irma Pereira, author2=Tracy I. George, author3=Daniel A. Arber, title=Atlas of Peripheral Blood: The Primary Diagnostic Tool, chapter-url=https://books.google.com/books?id=o8Y9HANLdZcC&pg=PA185, date=7 December 2011, publisher=Lippincott Williams & Wilkins, isbn=978-1-4511-6366-7, chapter=Chapter 20: Nonhematopoietic tumors in the blood, pages=185–7 {{cite journal, last1=Johnsrud, first1=Andrew J., last2=Pina-Oviedo, first2=Sergio, title=Carcinocythemia (carcinoma cell leukemia), journal=Blood, volume=130, issue=21, year=2017, pages=2357, issn=0006-4971, doi=10.1182/blood-2017-08-799882, pmid=29170195, doi-access=free {{cite book, author1=Michael Caligiuri, author2=Marcel M. Levi, author3=Kenneth Kaushansky, author4=Marshall A. Lichtman, Josef Prchal, Linda J Burns, Oliver W Press, title=Williams Hematology, 9E, url=https://books.google.com/books?id=6MuXnQAACAAJ, date=23 December 2015, publisher=McGraw-Hill Education, isbn=978-0-07-183300-4, page=658 {{cite book, author1=Noel Weidner, author2=Richard J. Cote, author3=Saul Suster, author4=Lawrence M. Weiss, title=Modern Surgical Pathology, url=https://books.google.com/books?id=s857Bj3NKEkC&pg=PA1593, date=8 July 2009, publisher=Elsevier Health Sciences, isbn=978-1-4377-1958-1, pages=1593– {{cite journal, last1=Krishnamurthy, first1=Savitri, title=The emerging role of circulating tumor cells in breast cancer, journal=Cancer Cytopathology, volume=120, issue=3, year=2012, pages=161–166, issn=1934-662X, doi=10.1002/cncy.20207, pmid=22275137, s2cid=36422597 , doi-access=free {{cite journal, last1=Ronen, first1=Shira, last2=Kroft, first2=Steven H., last3=Olteanu, first3=Horatiu, last4=Hosking, first4=Paul R., last5=Harrington, first5=Alexandra M., s2cid=52278041, title=Carcinocythemia: A rare entity becoming more common? A 3-year, single institution series of seven cases and literature review, journal=International Journal of Laboratory Hematology, volume=41, issue=1, year=2019, pages=69–79, issn=1751-5521, doi=10.1111/ijlh.12924, pmid=30216684, doi-access=free {{cite journal, last1=Sá e Lemos, first1=Eva, last2=Lima de Carvalho, first2=Hugo, last3=Gil da Costa, first3=Rui M., last4=Pinto da Cunha, first4=Nazaré, title=Carcinocythemia: First report in a cat and literature review, journal=Veterinary Clinical Pathology, volume=47, issue=1, year=2018, pages=142–145, issn=0275-6382, doi=10.1111/vcp.12565, pmid=29360147 {{cite journal, last1=Chang, first1=Yuan-Hsin, last2=Hsieh, first2=Ruey-Kuen, last3=Chang, first3=Ming-Chi, last4=Chen, first4=Gon-Shen, s2cid=20417675, title=Breast cancer with an unusual leukemia-like presentation: case report and literature review, journal=Medical Oncology, volume=25, issue=1, year=2007, pages=100–103, issn=1357-0560, doi=10.1007/s12032-007-0048-2, pmid=18188722 {{cite journal , title=(1869) A Case of Cancer in Which Cells Similar to Those in the Tumours Were Seen in the Blood after Death , journal=The Medical Journal of Australia , year=1869 , last=Ashworth , first=T.R. , volume=14 , pages=146–147 {{cite journal, last1=Carey, first1=Robert W., last2=Taft, first2=Priscilla D., last3=Bennett, first3=John M., last4=Kaufman, first4=Sheldon, title=Carcinocythemia (carcinoma cell leukemia), journal=The American Journal of Medicine, volume=60, issue=2, year=1976, pages=273–278, issn=0002-9343, doi=10.1016/0002-9343(76)90437-X, pmid=1062163 {{cite journal, author=Lugassy G, Vorst EJ, Varon D, Sigler E, Shani A, Bassous-Guedj L., title=Carcinocythemia. Report of two cases, one simulating a Burkitt lymphoma. , journal=Acta Cytol , year= 1990 , volume= 34 , issue= 2 , pages= 265–8 , pmid=2157324 , url=https://pubmed.ncbi.nlm.nih.gov/2157324 {{cite journal, last1=Gallivan, first1=Monica V. E., last2=Lokich, first2=Jacob J., title=Carcinocythemia (carcinoma cell leukemia). Report of two cases with english literature review, journal=Cancer, volume=53, issue=5, year=1984, pages=1100–1102, issn=0008-543X, doi=10.1002/1097-0142(19840301)53:5<1100::AID-CNCR2820530514>3.0.CO;2-K, pmid=6362836, doi-access=free

External links

Images of carcinocythemia at the American Society of Hematology image bank
Hematopathology Leukemia Rare diseases