Lennert's Lymphoma
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Lennert lymphoma, also termed lymphoepithelioid lymphoma, lymphoepithelioid variant of peripheral T-cell lymphoma, and epithelioid cellular lymphogranulomatosis, is a rare subtype of the
T cell lymphoma T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. Lymphoma arises mainly from the uncontrolled proliferation of lymphocytes, such as T-cells, and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin lymphom ...
s. It was first characterized by Karl Lennert in 1952 as a variant of
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...
based on the presence of cells resembling the
Reed–Sternberg cell Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are distinctive, giant cells found with light microscopy in biopsies from individuals with Hodgkin lymphoma. They are usually derived from B lymphocytes, classicall ...
s that typify Hodgkin lymphoma.Lennert K: Zur Histologischen Diagnose der Lymphogranulomatose. Frankfurt, FRG, Habil-Schrift, 1952 However, later studies concluded that these cells are not Reed-Sternberg cells and that Lennert lymphoma is not a variant of Hodgkin lymphoma. Lennert lymphoma is now regarded as one form of the
peripheral T-cell lymphoma Peripheral T-cell lymphoma refers to a group of T-cell lymphomas that develop away from the thymus or bone marrow. Examples include: * Cutaneous T-cell lymphomas * Angioimmunoblastic T-cell lymphoma * Extranodal natural killer/T-cell lymphoma, ...
s. The
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(2016) classified these peripheral T-cell lymphomas into more than 25 different subtypes such as the
anaplastic large-cell lymphoma Anaplastic large-cell lymphoma (ALCL) refers to a group of non-Hodgkin lymphomas in which aberrant T cells proliferate uncontrollably. Considered as a single entity, ALCL is the most common type of peripheral lymphoma and represents ~10% of all per ...
(including its ALK+ and ALK- subtypes),
angioimmunoblastic T-cell lymphoma Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT, formerly known as "angioimmunoblastic lymphadenopathy with dysproteinemia") is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lym ...
, and
peripheral T-cell lymphoma not otherwise specified Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells c ...
. Peripheral T-cell lymphomas not otherwise specified include Lennert Lymphoma as well as several other lymphoma subtypes. However, the criteria used for diagnosing Lennert lymphomas has varied between different studies. That is, Lennert lymphoma has been defined using different microscopic histologies and immunochemistries (i.e., proteins expressed by tumor cells). Descriptions of the clinical features, prognoses, and survival times for Lennert lymphomas have also varied across different reports. Here, Lennert lymphoma is reviewed based on studies that used criteria to define this lymphoma which future studies may find are indicative of another type of lymphoma. Studies that question the identity of the "Lennert lymphomas" diagnostic criteria and other features used in different studies are included in this review.


Clinical presentation

While the great majority of patients with Lennert lymphoma present with swollen
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
, they also present with other symptoms in addition to, or without, obvious lymph node enlargements. In a review study of 26 patients (i.e., 15 men and 11 women,
median The median of a set of numbers is the value separating the higher half from the lower half of a Sample (statistics), data sample, a statistical population, population, or a probability distribution. For a data set, it may be thought of as the “ ...
age 72 years, range from 44 to 90 years) diagnosed with Lennert lymphoma: a) 7 presented with
B symptoms B symptoms are a set of symptoms, namely fever, night sweats, and unintentional weight loss, that can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. These symptoms are not specific to lymphomas, especially each one considered ...
(i.e., fever,
night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...
, and/or unintentional weight loss); b) 8 presented with (or later acquired) cancer cells in their
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 ...
, blood, skin, liver, lung, bone, and/or
subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, or superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and ma ...
in addition to their lymph nodes; c) 6 presented with hepatosplenomegaly (i.e., enlargement of both the liver and spleen) in addition to their lymph nodes; d) 5 had a 2 or 3 score on the ECOG/WHO/Zubrod questionnaire (i.e., they stayed in bed some or most of the day) at presentation; and e) 16 had a 3 or 4 on the
International Prognostic Index The International Prognostic Index (IPI) is a clinical tool developed by oncologists to aid in predicting the prognosis of patients with aggressive non-Hodgkin lymphoma. Previous to IPI's development, the primary consideration in assessing progno ...
(i.e., they had a projected 5 year survival of 43% or less) at presentation. The extent of disease at presentation of Lennert lymphoma uses the same
Ann Arbor staging Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (formerly designated Hodgkin's disease) and non-Hodgkin lymphoma (abbreviated NHL). It was initially developed for Hodgkin's, but has some use in NHL. It has roughly ...
system employed for all non-Hodgkin lymphomas: Stage I, involvement of a lymph node region or a single set of lymph nodes or a single tissue site in the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
; Stage II, involvement of multiple lymph node sites, other tissue in the lymphatic system, and/or non-lymphatic tissues all of which are on the same side of the
thoracic diaphragm The thoracic diaphragm, or simply the diaphragm (; ), is a sheet of internal Skeletal striated muscle, skeletal muscle in humans and other mammals that extends across the bottom of the thoracic cavity. The diaphragm is the most important Muscles ...
; Stage III, involvement of lymph nodes, other tissue in the lymphoid system, and/or non-lymphoid tissues with at least one of the sites being on the opposite side of the diaphragm from the other sites; Stage IV, disseminated disease occurring on both sides of the thoracic diaphragm and involving one or more non-lymphatic organs or all cases in which the liver and/or
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 ...
is/are involved. Among the 26 patients in the review study, 2 had not been staged, 1 had Stage I, 5 had Stage II, 9 had Stage III, 8 had stage IV, and 1 had stage III or IV disease. A later study of 10 patients (9 males, 1 female; mean age of 48.7, range 22–67 years) reported that: 1 presented with B symptoms, 1 presented with bone marrow involvement, 2 presented with involvement of tissues outside of their lymph nodes, 3 had bulky disease, and 4 had a
mediastinal tumor A mediastinal tumor is a tumor in the mediastinum, the cavity that separates the lungs from the rest of the chest. It contains the heart, esophagus, trachea, thymus, and aorta. The most common mediastinal masses are thymoma (20% of mediastinal tumo ...
that was not further defined. A 2009 review reported on one patient and 11 previously reported patients with Lennert lymphomas that invaded their skin. These skin lesions were asymptomatic, non-ulcerated, and red to violet
papules A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some ...
,
nodules Nodule may refer to: *Nodule (geology), a small rock or mineral cluster *Manganese nodule, a metallic concretion found on the seafloor *Nodule (medicine), a small aggregation of cells *Root nodule Root nodules are found on the roots of plants, p ...
, or small plaques on the trunk and limbs. In a more recent report, one patient with Lennert lymphoma had symptomatic skin lesions: the skin patches itched, felt warm, were located on the back of the neck, back, and buttocks, and on microscopic examination were infiltrated with Lennert lymphoma cells. Another recent study reported that a 65 year old patient had a painless
subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, or superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and ma ...
Lennert lymphoma but no evidence that it had invaded the nearby bone or skin surface nor that it was present in his lymph nodes, It was suggested that this Lennert lymphoma originated in the subcutaneous soft tissue rather than
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
.


Follicular helper T cell lymphoma

In the study of 26 patients with Lennert lymphoma, 15 had tumor cells that expressed one or more of the three proteins expressed by follicular helper T cells, ''viz.''
PD-1 Programmed cell death protein 1 (PD-1), (CD279 cluster of differentiation 279). PD-1 is a protein encoded in humans by the ''PDCD1'' gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's re ...
,
CXCL13 Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the ''CXCL13'' gene. Function CXCL13 is a small chemokine ...
, and
CD10 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'' ge ...
. These patients had a more severe form of Lennert lymphoma as defined by there survival times: the percentage of patients surviving 52 months after the diagnosis in the 15 patients with tumor cells that had one or more of these marker proteins was 33%, i.e., 5 of 15 patients, while it was 73%, i.e., 8, of the 11 patients, that lacked tumor cells with one or more of these maker proteins. This difference was statistically significant (
p-value In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means ...
of 0.011) based on the Logrank test and
Kaplan–Meier estimator The Kaplan–Meier estimator, also known as the product limit estimator, is a non-parametric statistic used to estimate the survival function from lifetime data. In medical research, it is often used to measure the fraction of patients living f ...
for the survival curves of the two patient groups. It should be noted, however, that other studies suggest that "Lennert lymphomas" with features of follicular helper T cell-bearing lymphomas are best defined as follicular helper T-cell lymphomas or
angioimmunoblastic T cell lymphoma Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT, formerly known as "angioimmunoblastic lymphadenopathy with dysproteinemia") is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lym ...
s rather than Lennert lymphomas.


Human T-cell lymphotropic virus type 1

Globally, the number of individuals infected with the human T-cell lymphotropic virus type 1 is estimated to be 5-10 million. These individuals reside principally in this virus's endemic areas, i.e., Japan (mainly the islands of
Kyushu is the third-largest island of Japan's Japanese archipelago, four main islands and the most southerly of the four largest islands (i.e. excluding Okinawa Island, Okinawa and the other Ryukyu Islands, Ryukyu (''Nansei'') Ryukyu Islands, Islands ...
and
Shikoku is the smallest of the List of islands of Japan#Main islands, four main islands of Japan. It is long and between at its widest. It has a population of 3.8 million, the least populated of Japan's four main islands. It is south of Honshu ...
), sub-Saharan Africa, South America, the Caribbean area, Iran, Romania, and Melanesia. This virus causes
adult T-cell leukemia/lymphoma Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 ( HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role ...
,
tropical spastic paraparesis Tropical spastic paraparesis (TSP), is a medical condition that causes weakness, muscle spasms, and sensory disturbance by human T-lymphotropic virus resulting in paraparesis, weakness of the legs. As the name suggests, it is most common in Tropics ...
, and various inflammatory disorders such as
uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
and
dermatitis Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...
. Clinically and histopathologically, T-cell leukemia/lymphoma may mimic and therefore be misdiagnosed as other types of T-cell neoplasms including Lennert lymphoma. One large study suggested that in diagnosing Lennert lymphomas tests should be conducted to determine the presence of the human T-cell lymphotropic virus type 1, particularly in individuals living in or coming from this virus's endemic areas. The presence of the virus in Lennert lymphoma-like tissues indicates that the lymphoma is an adult T-cell leukemia/lymphoma rather than a Lennert lymphoma.


Epstein-Barr virus

The Epstein-Barr virus infects about 95% of the world's population. It initially causes
infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...
, non-specific symptoms, or no symptoms but nonetheless enters a latency period in its hosts and thereafter may become active in causing a wide range of lymphoproliferative diseases termed
Epstein–Barr virus–associated lymphoproliferative diseases Epstein–Barr virus–associated lymphoproliferative diseases (also abbreviated EBV-associated lymphoproliferative diseases or EBV+ LPD) are a group of disorders in which one or more types of lymphoid cells (a type of white blood cell), i.e ...
as well as various other diseases (see The role of EBV in disease). An early study reported that 11 of 15 patients expressed Epstein-Barr virus
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
in their Lennert lymphoma tissues. Other studies have reported that this virus is less prevalent in Lennert lymphomas. For example, more recent studies have reported that 8 of 26 patients, 4 of 13 patients, 1 of 10 patients, and none of 6 patients expressed the products made by the Epstein-Barr virus in their Lennert lymphoma tissues. The significance of the presence of the Epstein-Barr virus in Lennert lymphoma is unclear: studies have suggested that its presence in Lennert lymphoma cells is probably not directly involved in its development or severity or, alternatively, is associated with a more severe form of this lymphoma and shorten survival times.


Histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

The
microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale betwe ...
examination of Lennert lymphoma tissues commonly shows numerous
granuloma A granuloma is an aggregation of macrophages (along with other cells) that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such sub ...
-like aggregates of epithelioid histiocytes intermingled with varying numbers of
T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
and
B cells B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
(i.e., subtypes of
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and ...
). However, some cases of Lennert lymphoma consist of: a) epithelioid histiocytes intermingled with small, similarly appearing, lymphoid cells but without distinct granuloma or b) abundant histiocytic clusters and medium to large sized, atypical lymphoid cells. In one study, more than 90% of the T cells in the Lennert lymphoma tissues expressed Cd3, i.e., a
protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple active site, catalytic domains are found in a single polypeptide chain. ...
that is a
co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate Ligand (biochemistry), ligand recognition and initiate biological processes, such as entry of a pathogen into a host ...
on T cells. In the study of 26 patients with Lennert lymphomas, all 26 patients' lymphomas had CD3-expressing cells, 24 had
CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...
-expressing cells, and 5 had
CD8 CD8 (cluster of differentiation 8) is a transmembrane protein, transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell Cell signaling, signaling and aid ...
-expressing cells. CD4 is a membrane
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
receptor expressed on
helper T-cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
s; and CD8 is a
transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate Ligand (biochemistry), ligand recognition and initiate biological processes, such as entry of a pathogen into a host ...
for the
T-cell receptor The T-cell receptor (TCR) is a protein complex, located on the surface of T cells (also called T lymphocytes). They are responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. ...
on T cells.


Cytogenetics and gene expressions

Lennert lymphoma tissue samples from 15 patients were cultured and the
chromosomes A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...
in
metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, alig ...
were analyzed using a standard
G banding G-banding, G banding or Giemsa banding is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosomes. It is the most common chromosome banding method. It is useful for identifying genetic diseases (mainly chr ...
protocol. The lymphoma tissues of 7 patients exhibited a normal
karyotype A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...
, i.e., a normal appearing and complete set of chromosomes. However, eight patients' lymphoma tissues had various chromosome
cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...
abnormalities: two had
trisomy A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprod ...
of
chromosome 7 Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...
plus an extra
X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
, one had trisomy of
chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...
and
chromosome 5 Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 182 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. Ch ...
, one had trisomy of chromosome 3 and
chromosome 7 Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...
plus an additional X chromosome, one had trisomy of
chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...
, and three had additions and/or deletions to parts of multiply chromosomes. An analysis of pre-selected genes found 455 genes that expressed different levels of these genes'
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
or protein products in the tumor tissues of Lennert lymphoma ''versus'' the group of non-Lennert peripheral T-cell lymphoma not otherwise specified tumor tissues: 385 of these products were more highly express in Lennert lymphoma than the group of non-Lennert peripheral T-cell lymphoma not otherwise specified tumor tissues. These findings, if confirmed and further refined in future studies, would be extremely helpful in making the diagnosis of Lennert lymphoma.


Cancer cells in Lennert lymphoma

A 1986 study cited 11 publications which suggested that the cancer cells in Lennert lymphoma were T cells. The study agreed with this suggestion based on finding that their patient with Lennert lymphoma had a small portion of tumor tissue T cells which were hypotetraploid, i.e., missing one or more chromosomes. The study suggested that this small percentage of T cells were the malignant cells in Lennert lymphoma. In the same year, a study co-authored by Karl Lennert found that the T4-expressing lymphocytes but not the other cells types in the Lennert lymphoma tissues of four patients were rapidly proliferating (i.e., rapidly growing and multiplying) based on their levels of the cell proliferation marker Ki-67. This study also found that some of these rapidly proliferating lymphocytes had morphological features found in cancerous lymphocytes. Based on these finding, the study suggested that the rapidly proliferating, T4-expressing T cells are the cancer cells in Lennert lymphomas. Another study also suggested that CD4-expressing T cells were the cancer cells in Lennert lymphomas based on their being the most prevalent T cells in the tumor tissues of 8 of 12 Lennert lymphoma cases. While studies agree that T cells are the malignant cell in Lennert lymphoma, the exact type of T cell that is cancerous in Lennert lymphoma is controversial. Studies have proposed that the malignant cells in Lennert Lymphoma are CD4-expressing
T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
whereas other studies have proposed that CD-4-expressing
cytotoxic T cells A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
are the malignant cells in this lymphoma. Further studies are needed to define the exact type of cell that is malignant in Lennert lymphoma.


Diagnosis

Due to the various characteristics used to define Lennert Lymphoma, the correct diagnosis of it can be difficult. For example, among 340 cases of peripheral T cell lymphoma not otherwise specified, 28 were diagnosed as Lennert lymphomas. However, the agreement on this diagnosis by 4 experts was only 58%. Currently, Lennert lymphoma is diagnosed based primarily on its clinical presentation, microscopic histopathology, 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 ...
(e.g., the expression of certain proteins such as CD3, CD4, and CD8 in the tumor cells). As indicated in previous sections, the diagnosis of Lennert lymphoma a) should test the tumor tissue for the presence of the human T-cell lymphotropic virus type 1 which, if present, indicates that this lymphoma is an adult T-cell leukemia/lymphoma and b) consider the possibility that the lymphoma is a follicular helper T-cell lymphoma or
angioimmunoblastic T cell lymphoma Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT, formerly known as "angioimmunoblastic lymphadenopathy with dysproteinemia") is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lym ...
if its tissues have appreciable numbers of follicular helper T-cells and/or other features of follicular helper T cell lymphomas.


Treatment and prognosis

Due to its rarity, varying definitions, and lack of
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
studies, the best treatment(s) for Lennert lymphoma are unclear. Consequently, these treatments have used drugs or other methods that have been used to treat other types of peripheral T-cell lymphomas. A study of 26 patients with Lennert lymphomas treated a) 13 patients with the CHOP regime of
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
,
doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
,
vincristine Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin lym ...
, and
prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...
; b) 9 patients with the THP-COP regimen of pirarubicin, cyclophosphamide, vincristine, and prednisolone); c) 1 patient with the CVP regimen of cyclophosphamide, vincristine, and prednisolone); d) 1 patient with
etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
; and e) 1 patient with
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s, One patient received no therapy. Eleven of the 24 patients treated with chemotherapy (i.e., omitting the patients treated with corticosteroids or untreated) had
complete Complete may refer to: Logic * Completeness (logic) * Completeness of a theory, the property of a theory that every formula in the theory's language or its negation is provable Mathematics * The completeness of the real numbers, which implies t ...
remissions or complete remissions, unconfirmed. Overall, 7 patients died of Lennert lymphoma or complications of their lymphomas, 2 died of causes unrelated to their lymphomas, and 5 dropped out during the follow-up period. With a
median The median of a set of numbers is the value separating the higher half from the lower half of a Sample (statistics), data sample, a statistical population, population, or a probability distribution. For a data set, it may be thought of as the “ ...
follow-up time of 23 months (range 1 to 71 months), 10 of these 26 patients were alive 52 months after starting their treatment. However, 15 of these patients had lymphomas that expressed one or more marker proteins suggesting that they were follicular helper T cell lymphomas (see above "Follicular helper T cell lymphoma" section). None of these patients were alive whereas 8 of the 11 patients with Lennert lymphomas that did not express one or more of these marker proteins were alive 52 months after beginning treatment. The Kaplan-Meier estimator indicated the survival of the 11 patients with tumors that did not bear these marker proteins was significantly (''
p-value In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means ...
''=0.011) longer than the 15 patients with tumors that did bear these marker proteins. Another study reported that of 5 patients treated with CHOP one had died from the disease 4.5 years after treatment and 4 were alive 5 years after treatment. This group of patients did not include those whose lymphomas were considered to be follicular helper T cell lymphomas. In another study, 29 patients with Lennert lymphoma and 292 patients with other types of Peripheral T-cell lymphomas not otherwise specified received a combination chemotherapy or in rare cases a single agent chemotherapy or no chemotherapy. The 14 year survival rates for patients with Lennert lymphoma, 56%, was significantly (''p-value''=003, Logrank test) greater than the 10% survival rate for patients with other types of peripheral T-cell lymphomas not otherwise specified. Patients found positive for the human T-cell lymphotropic virus type 1 on screening were not included in these study groups. A study of a patient with a forehead Lennert lymphoma without evidence of this lymphoma in other tissues was treated with cyclophosphamide,
liposome A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug deliver ...
-encapsulated doxorubicin, vincristine, and prednisone tablets. This patient had no evidence of recurrent disease 20 months after starting this therapy.


See also

*
Cutaneous T-cell lymphoma Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B cell, B-cell-related), CTCL is caused by a mutation of T cells. The ma ...
* Pleomorphic T-cell lymphoma *
Peripheral T-cell lymphoma-Not-Otherwise-Specified Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells c ...


References

{{Lymphoid malignancy Lymphoid-related cutaneous conditions Lymphoma