| Langerhans cell sarcoma | |
|---|---|
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| Langerhans cell sarcoma as seen in this H&E stain | |
| Specialty | Oncology  |
Langerhans cell sarcoma (LCS) is a rare form of malignant histiocytosis. It should not be confused with Langerhans cell histiocytosis, which is cytologically benign. [1] It can present most commonly in the skin and lymphatic tissue, but may also present in the lung, liver, and bone marrow. [2] [3] Treatment is most commonly with surgery or chemotherapy. [3]
Dendritic cell neoplasms are classified by the World Health Organization as follows: [4]
The exact incidence of LCS is unknown due to the rarity of the condition. The related condition, Langerhans Cell Histiocytosis (LCH) is estimated to have an incidence of around 5 cases per 1 million people per year. [5] In one review of Japanese patients with confirmed LCS, patients were a median age of 41 years. [5] Patients were twice as likely to be female than male. [5] In another systematic review, the median age of presentation was 50 years, but with a slight predilection for males. [3]
Throughout the body in locations such as mucous membranes, skin, lymph nodes, thymus, and spleen are cells known as antigen-presenting cells. These cells are surveillance cells that take foreign antigens and present them to antigen-processing cells, such as T-cells, protecting the body from potential harm. [6] [7] Antigen-presenting cells are also termed Dendritic cells, of which Langerhans cells are a subtype. [6] There are four main types that make up the structure and functions of lymphoid tissue, such as lymph nodes and splenic tissue. [4] By definition, Langerhans Cell Sarcoma (LCS) is a cancerous disease caused by the uncontrolled overproliferation of Langerhans cells. [5]
Because Langerhans cells are most commonly found in the mucosa and the skin, LCS is thought to usually begin here with further spread to other areas of the body via the lymphatic system. [3]
Langerhans cell sarcoma can occur de novo, or can occur as a malignant transformation of Langerhans cell histiocytosis. [3] [8]
The related condition, LCH, presents with various clinical features depending on the bodily organs involved. [5] LCS shares most of these clinical presentations. Most commonly, these patients will present with generalized signs and symptoms such as fever and weight loss. [5] Blood tests will commonly show pancytopenia, an overall reduction in blood cell counts. [5] Additionally, these patients may display lymphadenopathy, hepatosplenomegaly, skin lesions, bone lesions, and lung lesions. [5] Most common site presentations are the skin and lymphatics. [6] [3] Other common sites of involvement include the lung, liver, and spleen. [3]
LCS will present with a varied gross appearance. When involving the skin, LCS will present as a patches of erythema, with nodules and ulceration present as well. [9] Skin lesions will most commonly involve the trunk, scalp, and legs. [9] Tumor size may range from 1-6 cm, but may be larger. Usually the tumor is well circumscribed with a surface covered in small nodules or protuberances. Most are of a solid consistency and are of a pink, white, or tan color. LCS tumors may present with much larger sizes and aggressive features, even causing some bleeding and necrosis of the surrounding tissue. [4]
Diagnosis of Langerhans Cell Sarcoma is predominantly a pathologic diagnosis. Cells from these tumor samples will display features characteristic of Langerhans cells, but with additional signs of malignancy, such as increased mitoses, cellular atypia, and pleomorphic nuclei. [5]
CD-207 is a cellular marker associated with Birbeck granules than can be used for confirmation of cell type. [5] LCS will also stain positive for CD-68, CD-68R, CD-21, CD-35, S-100, CD1a, lysozyme, HLA-DR, CD4, fascin, Factor XIIIa, and cyclin D1, which are cellular markers typically used in the characterization of various pathology specimens. [4] [5] [6] Positive staining with CD1a and S-100 are required for diagnosis of LCS. [4] Positive staining with CD-207 (Langerin) is an additional confirmation marker of malignancy in LCS. [6] [3] [9] Other cellular markers have been reported to be positive in LCS, but have are not as routinely used. [5]
Histologically, Langerhans cells characteristically display Birbeck granules and nuclei with a longitudinal groove. [5] [6] Birbeck granules are currently a poorly understood cellular structure, but are commonly used for cell-type identification. [10] Previously, the presence of Birbeck granules was necessary for diagnosis, but this is no longer considered diagnostic. [6]
Currently, there appears to be no relation of LCS with chromosomal abnormalities. [5]
The diagnosis of LCS can be difficult, especially due to its rarity. It has previously been mistaken with metastatic melanoma and metastatic large-cell carcinoma. [8]
Treatment for this rare disease consists of a variety of approaches, with none displaying any increased efficacy over another. [4] There are currently three broad treatment strategies for LCS: surgery, chemotherapy, and combination with radiation therapy. [3] When the LCS tumor is readily accessible, the best treatment method is usually surgical removal. [4] There is, however, an observed increased risk of tumor relapse following surgical resection. [4] Both chemotherapy and radiation therapy are useful as treatments, either as monotherapy or in conjunction with other treatments. [6] [3] Chemotherapy is currently the most common treatment method, either alone or in combination. [3] The most common chemotherapeutic regimen consisted of cyclophosphamide, doxorubicin, vincristine, and prednisolone (otherwise known as CHOP therapy). [3] Other common chemotherapeutic regimens include MAID (mesna, doxorubicin, ifosfamide, and dacarbazine), ESHAP (etoposide, carboplatin, cytarabine, and methylprednisolone), EPIG (etoposide, cisplatin, ifosfamide, mesna, and gemcitabine), and AIM (doxorubicin, ifosfamide, and mesna). [8] Other regimens have been used with mixed levels of success. [3] In an effort to prevent recurrence, sometimes combination therapy is used. Following surgical resection, additional radiation therapy or chemotherapy may be performed to prevent relapse. [4] Patients receiving combined chemotherapy and radiation therapy has only shown limited benefit. [4]
There are a variety of other therapies under research with varying levels of reported success. These include high-dose chemotherapy, bone marrow transplants, and somatostatin analogues. [4] [3]
When there is only one site of LCS involvement, monotherapy may be sufficient treatment. But when the disease has multiple sites or has metastasized, combination therapy will be necessary to achieve any level of adequate treatment. [6]
Overall prognosis of patients with LCS depends heavily on the bodily organ involved and the extent of involvement of the tumor. [5] Organs associated with a poor prognosis include the liver, lungs, and bone marrow. [5] In patients with a single site of involvement, survivability tends to be very favorable. [6] However, those with multi-organ involvement have a mortality rate of 50-66%. [5] One systematic review calculated the disease-specific survival as 27.2 months, or 58% at one year. [3] One group found the death rate to be 50% in patients with LCS, compared to 31% in patients who had the related condition LCH. [1] Survivability decreases dramatically with increased disease burden and spread. [3] LCS may be associated with other malignancies as well, such as follicular lymphoma, adenocarcinoma, and germ cell tumors. [4] Evidence of metastatic disease or relapse from a previously treated LCS usually signifies a worsened prognosis. [4] Treatment of these metastatic lesions or relapsed tumors may improve the patient's prognosis, but there is limited evidence as to a preferred therapy. [4]
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates. Sarcomas are primary connective tissue tumors, meaning that they arise in connective tissues. This is in contrast to secondary connective tissue tumors, which occur when a cancer from elsewhere in the body spreads to the connective tissue. The word sarcoma is derived from the Greek σάρκωμα sarkōma "fleshy excrescence or substance", itself from σάρξsarx meaning "flesh".
Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas and 18 percent of all cutaneous soft tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma.
A myeloid sarcoma is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow.
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as in the mucosa of the mouth, foreskin, and vaginal epithelium. They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).
Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes.
Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.
Letterer–Siwe disease, (LSD) or Abt-Letterer-Siwe disease, is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH) and is the most severe form, involving multiple organ systems such as the skin, bone marrow, spleen, liver, and lung. Oral cavity and gastrointestinal involvement may also be seen. LCH and all its subtypes are characterized by monoclonal migration and proliferation of specific dendritic cells.
Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.
Juvenile xanthogranuloma is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".
Chronic multifocal Langerhans cell histiocytosis, previously known as Hand–Schüller–Christian disease, is a type of Langerhans cell histiocytosis (LCH), which can affect multiple organs. The condition is traditionally associated with a combination of three features; bulging eyes, breakdown of bone, and diabetes insipidus, although around 75% of cases do not have all three features. Other features may include a fever and weight loss, and depending on the organs involved there maybe rashes, asymmetry of the face, ear infections, signs in the mouth and the appearance of advanced gum disease. Features relating to lung and liver disease may occur.
Rosai–Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy or sometimes as Destombes–Rosai–Dorfman disease, is a rare disorder of unknown cause that is characterized by abundant histiocytes in the lymph nodes or other locations throughout the body.
Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limited area, or may be widespread. Depending on the sub-type of disease and level of immune suppression, KS may worsen either gradually or quickly. Except for Classical KS where there is generally no immune suppression, KS is caused by a combination of immune suppression and infection by Human herpesvirus 8.
Blueberry muffin baby, also known as extramedullary hematopoiesis, describes a newborn baby with multiple purpura, associated with several non-cancerous and cancerous conditions in which extra blood is produced in the skin. The bumps range from 1-7mm, do not blanche and have a tendency to occur on the head, neck and trunk. They often fade by 3 to 6 weeks after birth, leaving brownish marks. When due to a cancer, the bumps tend to be fewer, firmer and larger.
Follicular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm. While the existence of FDC tumors was predicted by Lennert in 1978, the tumor wasn't fully recognized as its own cancer until 1986 after characterization by Monda et al. It accounts for only 0.4% of soft tissue sarcomas, but has significant recurrent and metastatic potential and is considered an intermediate grade malignancy. The major hurdle in treating FDCS has been misdiagnosis. It is a newly characterized cancer, and because of its similarities in presentation and markers to lymphoma, both Hodgkin and Non-Hodgkin subtypes, diagnosis of FDCS can be difficult. With recent advancements in cancer biology better diagnostic assays and chemotherapeutic agents have been made to more accurately diagnose and treat FDCS.
Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare; the most common bone tumor is a metastasis Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
Histiocytic diseases in dogs are a group of diseases in dogs which may involve the skin, and which can be difficult to differentiate from granulomatous, reactive inflammatory or lymphoproliferative diseases. The clinical presentation and behaviour as well as response to therapy vary greatly among the syndromes.
Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin attached to an acid-sensitive linker.
Myxofibrosarcoma (MFS), although a rare type of tumor, is one of the most common soft tissue sarcomas, i.e. cancerous tumors, that develop in the soft tissues of elderly individuals. Initially considered to be a type of histiocytoma termed fibrous histiocytoma or myxoid variant of malignant fibrous histiocytoma, Angervall et al. termed this tumor myxofibrosarcoma in 1977. In 2020, the World Health Organization reclassified MFS as a separate and distinct tumor in the category of malignant fibroblastic and myofibroblastic tumors.
Dermatofibrosarcoma protuberans, fibrosarcomatous (DFSP-FS), also termed fibrosarcomatous dermatofibrosarcoma protuberans, is a rare type of tumor located in the dermis. DFSP-FS tumors have been viewed as: 1) a more aggressive form of the dermatofibrosarcoma protuberans (DFSP) tumors because they have areas that resemble and tend to behave like malignant fibrosarcomas or 2) as a distinctly different tumor than DFSP. DFSP-FS tumors are related to DFSP. For example, surgically removed DFSP tumors often recur with newly developed fibrobosarcoma-like areas. Nonetheless, the World Health Organization (WHO), 2020, classified DFSP and DFSP-FS as different tumors with DFSP being in the category of benign and DFSP-FS in the category of rarely metastasizing fibroblastic and myofibroblastic tumors. This article follows the WHO classification: the 5-15% of DFSP tumors that have any areas of fibrosarcomatous microscopic histopathology are here considered DFSP-FS rather than DFSP tumors.