Mycosis fungoides

(medicine) A lymphoma of the skin, usually present in several sites when first diagnosed, that may remain confined to the skin for 10 or more years before eventually spreading to internal organs and causing death.

Key Terms: Acyclovir, Antibody, Biopsy, Computed tomography, Cutaneous T-cell lymphoma, Electron beam, Hypericin, Interferon alpha, Local anesthetic, Lymph node, Myelosuppression, Oncologist, Pancreatitis, Pathologist, Precancerous, Remission, Retinoids, T lymphocyte or T cell, Ultraviolet light.

Definition

Mycosis fungoides is a skin cancer characterized by patches, plaques, and tumors where cancerous T lymphocytes have invaded the skin.

Description

Mycosis fungoides, the most common type of cutaneous T-cell lymphoma, originates from a type of white blood cell called a T lymphocyte or T cell. In mycosis fungoides, cancerous T cells accumulate in the skin. These cells and the skin irritation they create become visible as growths or changes in the skin's color or texture.

Mycosis fungoides usually develops and progresses slowly. It often begins as an unexplained rash that can wax and wane for years. Whether this stage represents early mycosis fungoides or a precancerous stage is controversial. The classic symptoms of mycosis fungoides are red, scaly skin patches that develop into raised plaques, then into large, mushroom-shaped tumors. The patches often originate on parts of the body that are covered by clothing and sometimes improve when they are exposed to sunlight. Itching can be intense.

As the cancer progresses, the cancer cells lose their affinity for the skin and spread to nearby lymph nodes and other internal organs. The normal T cells also start to disappear. Because T cells are very important in immunity, this leaves the patient susceptible to infections. Treatment at an earlier stage of the disease can often stop or slow this progression.

Sézary syndrome is a variant of mycosis fungoides. Sézary syndrome is characterized by red, thickened skin and large numbers of cancer cells in the blood.

Demographics

Mycosis fungoides is usually diagnosed after the age of 50, but has been seen as early as childhood. Mycosis fungoides develops twice as often in men as in women and is more common in people of African than of European origin.

Causes and Symptoms

Environmental chemicals, virus infections, allergies, and genes have all been suggested as possible causes of this cancer. As of 2001, there is little concrete evidence to favor any of these possibilities.

The symptoms of mycosis fungoides include:

• Patches: patches are red or brown, sometimes scaly, flat areas. There may be one patch or many. Patches may itch and can resemble psoriasis, eczema, allergies, or other skin diseases. Some patients do not have a patch stage.
• Plaques: plaques are red or brown, sometimes scaly, raised areas. Itching is usually more intense than during the patch stage. The hair sometimes falls out in the affected skin. If the face is involved, the facial features can change.
• Tumors: tumors can originate from plaques, red skin, or normal skin. They are usually reddish brown or purple. The itching can diminish, but the tumors may develop painful open sores or become infected. Some tumors can become very large. Patches, plaques, and tumors can co-exist.
• Erythrodermic form: in the erythrodermic form, the skin becomes red, thickened, and sometimes peels and flakes. The palms and soles thicken and may crack. Itching is usually intense. More than 90% of the time, the erythrodermic form is associated with Sézary syndrome.
• Other, more rare symptoms are also seen, including itching alone.

Diagnosis

A physical examination, history of the symptoms, blood tests, and skin biopsy are usually the key to diagnosing this cancer. The blood tests examine the health of the internal organs and look for cancer cells in the blood. The skin biopsy checks for the typical microscopic changes seen in this disease. This biopsy is a brief, simple procedure often done in the doctor's office. After numbing the skin with an injection of local anesthetic, the doctor snips out one or more tiny pieces of abnormal skin. The skin samples are sent to a trained pathologist for examination, and results may take up to a week to come back.

During its early stages, mycosis fungoides can be very difficult to diagnose. The symptoms resemble other skin diseases and numerous biopsies may be needed before the typical features are found. Special stains and DNA tests on the skin sample may find the cancer a little earlier.

To stage this cancer, the lymph nodes are checked for abnormal size or texture and, if necessary, biopsied. The doctor may also recommend x-ray studies of the chest, computed tomography, or biopsies of the internal organs to look for cancer cells.

Treatment Team

Patients diagnosed with mycosis fungoides are often referred to an oncologist. A dermatologist may also become involved. Depending on the treatment chosen, the team may include other specialists, such as a radiation oncologist, specially trained nurses, a dietitian, or a social worker.

Clinical Staging, Treatments, and Prognosis

Staging

In stage I, the lymph nodes look normal and cancer cells cannot be found in the internal organs. In stage IA, patches or plaques cover less than 10% of the skin. In stage IB, they are present on more than 10%.

In stage IIA, some of the lymph nodes look swollen or abnormal. Patches or plaques may cover any amount of skin. In stage IIB, the lymph nodes may or may not look abnormal, but there is at least one tumor on the skin. Neither the lymph nodes nor the internal organs contain detectable cancer cells in stage IIA or IIB.

In stage III, the skin looks thickened, red and sometimes scaly. The lymph nodes sometimes look abnormal, but no cancer cells can be detected in them or within internal organs.

In stage IVA and IVB, the skin may have patches, plaques, tumors, or widespread reddening. In stage IVA, cancer cells have been found in the lymph nodes but not in other internal organs. In stage IVB, cancer cells have been found in internal organs and sometimes the lymph nodes.

Treatment

Mycosis fungoides is rarely cured. Instead, most treatments are aimed at controlling the symptoms, improving the quality of life, and preventing the disease from progressing into later stages. This cancer responds well to a variety of therapies and frequently goes into remission, particularly if it is caught early. Even in stage IV, treatment can significantly improve the symptoms in the skin.

In stages III and IV, treatments directed against the cancer cells in the skin may be combined with chemotherapy or other therapies against metastatic cells. Experimental treatments are sometimes offered, especially in stage III or stage IV. If the cancer relapses, retreatment may be possible or other therapies can be tried.

One treatment option for early cancers is ultraviolet B (UVB) light. UVB light can treat mycosis fungoides patches, but not plaques or tumors. About 70% of patients go into complete remission and 15% into partial remission. The side effects can include itching, sunburn, aging of the skin, and a risk of developing other skin cancers. The eyes must be protected from UVB light.

Psoralen and ultraviolet A (PUVA) photochemotherapy is an option for all stages, although earlier stages usually have a better response. In PUVA, the drug methoxypsoralen is taken before exposure to ultraviolet A (UVA) light. The drug sensitizes the cancer cells to the light. The complete remission rate with this treatment is 62–90%. The side effects may include itching, dry skin, sunburn, nausea, nail discoloration, and a risk of developing other skin cancers. The eyes must be protected to prevent damage to the retina and possibly cataracts.

Total skin electron-beam irradiation (TSEB) is also effective for all stages. TSEB is a type of radiation treatment that uses beams of electrons to irradiate the skin. The electrons stop at the skin and do not penetrate deeper tissues. Up to 80% of patients in stages II and III will respond. The side effects can include flaking of the skin, alopecia or hair loss (usually temporary), loss of sweat glands, skin irritation, blisters, dryness, temporary loss of the nails, and a risk of developing other skin cancers. These side effects limit the number of times this treatment can be given. TSEB is not available everywhere.

Other types of radiation—for instance, focused electron beam irradiation or x rays—can shrink or destroy some tumors or plaques.

Mechlorethamine (nitrogen mustard) is a drug that can be painted onto the skin to suppress the cancer. A thin layer is applied to the whole skin at bedtime, then washed off in the morning. The side effects can include dryness, skin irritation, darkening of the skin, allergies to the ingredients, and possibly a risk of other skin cancers. Half to 80% of mycosis fungoides patients in stage IA and 25–75% of patients in stage IB or IIA go into complete remission. In stage IIB, the complete remission rate is up to 50%. In stage III, it is 20–40% and, in stage IV, up to 35%. In stages III and IV, this treatment is used to decrease the skin symptoms and is often combined with other treatments.

Carmustine (BCNU) is an alternative drug. Its effectiveness is similar to mechlorethamine. In addition to side effects in the skin, this drug may cause myelosuppression.

Bexarotene is a drug used for cases that do not respond to other treatments. About 40% of patients have a complete or partial remission. The side effects may include dryness of the mucous membranes, aching joints or muscles, headaches, fatigue, and increased fragility of the skin. One of the most serious side effects is an increase in the fats in the blood, which can lead to pancreatitis.

Aldesleukin fusion toxin contains a poison that damages cells, attached to a molecule that directs that poison to T cells. About 10% of patients have complete remissions and 40% respond to some extent. The side effects can include chills, nausea, fluid retention, and allergic reactions to the drug.

Chemotherapy is sometimes combined with other therapies for stages III and IV. In stage IV, chemotherapy is directed against the metastatic cells in the lymph nodes or internal organs. Approximately 60% of mycosis fungoides patients in stage IV respond to single drugs, but the remission usually lasts less than six months. No cures have been reported, and it is not certain whether chemotherapy lengthens survival.

Corticosteroids are sometimes added to other treatments. These drugs decrease skin irritation and can destroy T cells. Fifty percent of patients have complete remissions on corticosteroids and 40% have partial remissions.

Supportive therapies can also help. Antihistamines or other drugs can decrease the itching. Mild moisturizing soaps and moisturizers can also combat the dryness and itching. If infection sets in, antibiotics may be necessary.

Prognosis

If mycosis fungoides is caught early, the prognosis is very good. If treatment begins during stage IA, most patients can expect to live as long as someone of the same age and gender who does not have this cancer. Median survival in stage IA is at least 20 years and most people die of diseases unrelated to the cancer. The overall 5-year survival in stage I is 80–90%. In stage II, five-year survival is 60–70%. As tumors develop and the cancer cells spread internally, the prognosis becomes worse. Five-year survival drops to 30% in stage IIB, 40–50% in stage III, and 25–35% in stage IV. Cancer cells can spread into almost any organ in the later stages of mycosis fungoides. Once this happens, many patients die of cancer complications, particularly skin infections that spread into the blood. Overall, half of mycosis fungoides patients live for at least 10 years after their cancer is diagnosed.

Alternative and Complementary Therapies

Complementary treatments can decrease stress, reduce the side effects of cancer treatment, and help patients feel more in control. For instance, some people find activities such as biofeedback, hypnosis, pet therapy, yoga, massage, pleasant distractions, meditation and prayer, mild physical exercise, or visualization helpful. Patients should check with their doctors before starting any complementary or alternative treatment. This is particularly important for alternative treatments that attempt to cure the cancer, boost the immune system, or reduce the side effects of conventional treatments. Some alternative treatments may interfere with the standard medical treatments or be dangerous when they are combined.

Coping With Cancer Treatment

Many of the treatments used for mycosis fungoides can dry and irritate the skin. Some ways to help are:

• Wear soft, loose clothing over the affected areas.
• Protect the skin from the sun.
• Don't scratch or rub the affected areas.
• Check with a doctor or nurse before using lotions, moisturizers, sunscreens, or cosmetics on the area.
• If allowed, use moisturizer and a moisturizing soap.

Clinical Trials

Because mycosis fungoides is unlikely to be cured with the standard treatments, all patients with this disease are candidates for clinical trials. Patients should check with their medical insurers before enrolling in a clinical trial. Insurers may not pay for some treatments; however, this varies with the insurer and each individual case.

Some clinical trials are testing new drugs, including some retinoids, acyclovir, and hypericin.

In extracorporeal photochemotherapy, the white blood cells are exposed to a chemical called a psoralen, temporarily separated from the rest of the blood and treated with UVA light, then returned to the body. This treatment may stimulate the immune system to destroy the cancer cells.

Interferon alpha is a drug that is injected into plaques and tumors. About 55% of patients have some response and 17% go into complete remission. The side effects may include fevers, fatigue, loss of appetite (anorexia), decreases in the number of white blood cells, or irregular heartbeats.

Antibodies can block important molecules on the cancer cells or carry poisons or radioactive molecules to the cancer.

Some clinical trials are testing whether bone marrow transplantation can produce lasting remissions.

Prevention

The risk factors for mycosis fungoides are unknown and there is no known means of prevention.

Questions to Ask the Doctor

• What stage is my cancer?
• If it is treated, is my cancer likely to progress?
• Which treatment(s) do you recommend?
• What are the side effects of these treatments?
• Can you recommend anything to help with those side effects?
• How should I prepare for the treatment?
• Are there any other treatments which might work as well?
• Do you expect me to go into remission and, if so, how long can I expect it to last?
• How often should I return for check-ups?

Special Concerns

Because mycosis fungoides is rarely cured, patients must usually return periodically for check-ups or treatments to maintain the remission. Between visits, patients should also be alert for skin infections. These infections can spread into the blood and become serious if they are not controlled. Because mycosis fungoides can affect the appearance, patients may wish to discuss cosmetic concerns with a doctor, other professional, or support group. Mycosis fungoides increases the risk of developing other types of lymphocyte cancers.

Resources

Books

Habermann, Thomas M., and Mark R. Pittelkow. "Cutaneous T-Cell Lymphoma." In Clinical Oncology, edited by Martin D. Abeloff, James O. Armitage, Allen S. Lichter, and John E. Niederhuber, 2nd ed. Philadelphia: Churchhill Livingstone, 2004, pp.2720-40.

Wood, Gary S., and Seth R. Stevens. "Cutaneous T Cell Lymphomas." In Conn's Current Therapy; Latest Approved Methods of Treatment for the Practicing Physician, edited by Robert E. Rakel, et al., 52nd ed. Philadelphia: W. B. Saunders, 2000, pp.766-70.

Periodicals

Duvic, Madeleine, and Jennifer C. Cather. "Emerging New Therapies for Cutaneous T-Cell Lymphoma." Dermatologic Clinics 18, no. 1 (January 2000): 147-55.

Elmer, Kathleen B., and Rita M. George. "Cutaneous T-Cell Lymphoma Presenting as Benign Dermatoses." American Family Physician 59, no. 10 (15 May 1999): 2809-13.

Pujol, Ramon M., Fernando Gallardo, Enric Llistosella, Aurora Blanco, Lluis Bernado, Ramon Bordes, Josep F. Nomdedeu, and Octavio Servitje. "Invisible Mycosis Fungoides: A Diagnostic Challenge." Journal of the American Academy of Dermatology 42, no. 2 (February 2000): 324-8.

Organizations

The Cutaneous Lymphoma Network. Judi Van Horn, R.N., Editor. c/o Department of Dermatology, University of Cincinnati, P.O. Box 670523, Cincinnati, OH 45267-0523. (513) 558-6805. This organization produces a newsletter with articles on this cancer, information on support groups, and opportunities for contact with other mycosis fungoides patients.

The Mycosis Fungoides Foundation. P.O. Box 374, Birmingham, MI, 48102-0374. (248) 644-9014. .

Other

"Mycosis Fungoides and the Sézary Syndrome Treatment—Health Professionals." CancerNet. National Cancer Institute. [cited June 7, 2005]. .

"Radiation Therapy and You: A Guide to Self-Help During Cancer Treatment." CancerNet. National Cancer Institute. [cited June 7, 2005]. .

—Anna Rovid Spickler, D.V.M., Ph.D.

A rare, chronic, lymphomatous skin malignancy resembling eczema or a cutaneous tumor that is followed by microabscesses in the epidermis and lesions simulating those of Hodgkin’s disease in lymph nodes and viscera.

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (July 2008)

Mycosis fungoides
Classification and external resources
Skin lesions on the knee of a 52 year old male patient with Mycosis fungoides
ICD-10	C84.0
ICD-9	202.1
ICD-O:	M9700/3
OMIM	254400
DiseasesDB	8595
eMedicine	med/1541
MeSH	[1]

Mycosis fungoides (also known as Alibert-Bazin syndrome^[1] or granuloma fungoides), is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time.

Mycosis fungoides was first described in 1806 by French dermatologist Jean-Louis-Marc Alibert.^[2] The name mycosis fungoides is somewhat misleading--it loosely means "mushroom-like fungal disease". The disease, however, is not a fungal infection but rather a type of non-Hodgkin's lymphoma. It was so named because Alibert described the skin tumors of a severe case as having a mushroom-like appearance.^[3]

Contents 1 History 2 Origins and causes 3 Symptoms, diagnosis, and stages 4 Treatments and cures 5 See also 6 References 7 Further reading 8 External links

History

In 1806, a French physician, Jean Louis Alibert, was the first to describe a patient with mycosis fungoides.^[4]

Origins and causes

The cause of mycosis fungoides is unknown, but it is not believed to be hereditary or genetic in the vast majority of cases. One incident has been reported of a possible genetic link ^[5]. It is not contagious.

It is rare for the disease to appear before age 20, and it appears to be noticeably more common in males than females, especially over the age of 50, where the incidence of the disease (the risk per person in the population) does increase. The average age of onset is between 45 and 55 years of age for patients with patch and plaque disease only, but is over 60 for patients who present with tumours, erythroderma (red skin) or a leukemic form (the Sézary syndrome).

The disease is an unusual expression of CD4 T cells, a part of the immune system. These T cells are skin-associated, meaning that they biochemically and biologically are most related to the skin, in a dynamic manner. Mycosis fungoides is the most common type of 'Cutaneous T-cell Lymphoma' (CTCL), but there are many other types of CTCL that have nothing to do with mycosis fungoides and these disorders are treated differently.

Symptoms, diagnosis, and stages

Typical visible symptoms include rashlike patches, tumors, or lesions^[3]. Itching (pruritus) is common, perhaps in 20% of patients, and is not universal.

Diagnosis is sometimes difficult because the early phases of the disease often resemble eczema or even psoriasis. As with any serious disease, it is advisable to pursue the opinion of a medical professional if a case is suspected. Diagnosis is generally accomplished through a skin biopsy. Several biopsies are recommended, to be more certain of the diagnosis. The diagnosis is made through a combination of the clinical picture and examination, and is confirmed by biopsy.

To stage the disease, various tests may be ordered, to assess nodes, blood and internal organs, but most patients present with disease apparently confined to the skin, as patches (flat spots) and plaques (slightly raised or 'wrinkled' spots).

Treatments and cures

Mycosis fungoides can be treated in a variety of ways.

If treatment is successful the disease can go into a non-progressing state with clinically clear examination and various tests. This is called remission; it can last indefinitely. Treatments may also cause disease not to progress, while still present, and this is called stable disease; it may last indefinitely but is a more serious situation. Disease may also progress, to involve nodes, blood and internal organs, or transform into a higher-grade lymphoma.

Common treatments include simple sunlight, ultraviolet light, topical steroids, topical and systemic chemotherapies, local superficial radiotherapy, the histone deacetylase inhibitor vorinostat, total skin electron beam radiation, and biological therapies (e.g. interferons, retinoids, rexinoids). Treatments are often used in combination.

Selection of treatments typically depends on patient preference and access to therapies, as well as recommendations by physicians, the stage of the disease, established resistance to prior therapies, allergies of the patient, clinical evidence of a positive benefit:risk ratio, and so on.

It is debatable whether cures are reliably obtained through different types of treatments, but many patients experience prolonged periods of disease-control and at least half of all patients do not die from this disease, even if not truly cured. Quality of life is a major objective, in addition to cure, and maximizing periods of remission or stable disease, while minimizing treatments and toxicities, are two central concerns in clinical care.

See also

• Cutaneous T-cell lymphoma
• Pagetoid reticulosis
• Premycotic phase
• Sézary's disease
• Secondary cutaneous CD30+ large cell lymphoma
• Angiocentric lymphoma

References

1. ^ synd/98 at Who Named It?
2. ^ Alibert JLM (1806) (in French). Descriptions des maladies de la peau observées a l’Hôpital Saint-Louis, et exposition des meilleures méthodes suivies pour leur traitement. Paris: Barrois l’ainé. p. 286. http://infohawk.uiowa.edu/F?func=direct&doc_number=000636854&l_base=uiowa. 
3. ^ ^{a b} Cerroni, Lorenzo; Kevin Gatter, Helmut Kerl (2005). An illustrated guide to Skin Lymphomas. Malden, Massachusetts: Blackwell Publishing. pp. 13. ISBN 978-1405113762. 
4. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1867. ISBN 1-4160-2999-0. 
5. ^ http://www.ncbi.nlm.nih.gov/pubmed/7425665?dopt=Abstract

Further reading

• Knowles Daniel M (2000). Neoplastic Hematopathology. Lippincott Williams Wilkins. p. 1957. ISBN 0683302469. 
• Hwang ST, Janik JE, Jaffe ES, Wilson WH (2008-03-15). "Mycosis fungoides and Sézary syndrome". Lancet 371 (9616): 945–957. doi:10.1016/S0140-6736(08)60420-1. PMID 18342689. 
• Duvic M, Foss FM (December 2007). "Mycosis fungoides: pathophysiology and emerging therapies". Semin Oncol 34 (6 Suppl 5): S21–S28. doi:10.1053/j.seminoncol.2007.11.006. PMID 18086343. 
• Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC (2007-09-15). "Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)". Blood 110 (6): 1713–1722. PMID 17540844. 

External links

• DermAtlas 197
• The Lymphoma Information Network - Cutaneous T-Cell Lymphomas
• The Doctor's Doctor (detailed information)
• Cutaneous Lymphoma Foundation (formerly MFF)
• ClinicalTrials.gov NCT00106431 "A Single Agent Phase II Study of Romidepsin (Depsipeptide, FK228) in the Treatment of Cutaneous T-Cell Lymphoma"

v • d • e Diseases of the skin and appendages by morphology Growths Epidermal wart · callus · seborrheic keratosis · acrochordon · molluscum contagiosum · actinic keratosis · squamous cell carcinoma · basal cell carcinoma · merkel cell carcinoma · nevus sebaceous · trichoepithelioma Pigmented Freckles · lentigo · melasma · nevus · melanoma Dermal and subcutaneous epidermal inclusion cyst · hemangioma · dermatofibroma · keloid · lipoma · neurofibroma · xanthoma · Kaposi's sarcoma · infantile digital fibromatosis · granular cell tumor · leiomyoma · lymphangioma circumscriptum · myxoid cyst Rashes With epidermal involvement Eczematous contact dermatitis · atopic dermatitis · seborrheic dermatitis · stasis dermatitis · lichen simplex chronicus · Darier's disease · glucagonoma syndrome · langerhans cell histiocytosis · lichen sclerosus · pemphigus foliaceus · Wiskott-Aldrich syndrome · Zinc deficiency Scaling psoriasis · tinea (corporis · cruris · pedis · manuum · faciei) · pityriasis rosea · secondary syphillis · mycosis fungoides · systemic lupus erythematosus · pityriasis rubra pilaris · parapsoriasis · ichthyosis Blistering herpes simplex · herpes zoster · varicella · bullous impetigo · acute contact dermatitis · pemphigus vulgaris · bullous pemphigoid · dermatitis herpetiformis · porphyria cutanea tarda · epidermolysis bullosa simplex Papular scabies · insect bite reactions · lichen planus · miliaria · keratosis pilaris · lichen spinulosus · transient acantholytic dermatosis · lichen nitidus · pityriasis lichenoides et varioliformis acuta Pustular acne vulgaris · acne rosacea · folliculitis · impetigo · candidiasis · gonococcemia · dermatophyte · coccidioidomycosis · subcorneal pustular dermatosis Hypopigmented tinea versicolor · vitiligo · pityriasis alba · postinflammatory hyperpigmentation · tuberous sclerosis · idiopathic guttate hypomelanosis · leprosy · hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized drug eruptions · viral exanthems · toxic erythema · systemic lupus erythematosus Localized cellulitis · abscess · boil · erythema nodosum · carcinoid syndrome · fixed drug eruption Specialized urticaria · erythema (multiforme · migrans · gyratum repens · annulare centrifugum · ab igne) Nonblanchable Purpura Macular thrombocytopenic purpura · actinic purpura Papular disseminated intravascular coagulation · vasculitis Indurated scleroderma/morphea · granuloma annulare · lichen sclerosis et atrophicus · necrobiosis lipoidica Miscellaneous disorders Ulcers Hair telogen effluvium · androgenic alopecia · trichotillomania · alopecia areata · systemic lupus erythematosus · tinea capitis · loose anagen syndrome · lichen planopilaris · folliculitis decalvans · acne keloidalis nuchae Nail onychomycosis · psoriasis · paronychia · ingrown nail Mucous membrane aphthous stomatitis · oral candidiasis · lichen planus · leukoplakia · pemphigus vulgaris · mucous membrane pemphigoid · cicatricial pemphigoid · herpesvirus · coxsackievirus · syphilis · systemic histoplasmosis · squamous cell carcinoma

v • d • e Hematological malignancy/leukemia histology (ICD-O 9590-9989, C81-C96, 200-208) Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590-9739, 9800-9839) B cell (lymphoma, leukemia) (most CD19, CD20) By development/ marker TdT+ ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ naive B cell (CLL/SLL) mantle zone (Mantle cell) CD22+ Prolymphocytic · CD11c (Hairy cell leukemia) CD79a+ germinal center/follicular B cell (Follicular, Burkitt's, GCB-DLBCL) marginal zone/marginal-zone B cell (Splenic marginal zone, MALT, Nodal marginal zone) RS (CD15+,CD30+) Classic Hodgkin's lymphoma (Nodular sclerosis) · CD20 (Nodular lymphocyte predominant Hodgkin's lymphoma) PCDs/PP (CD38+/CD138+) see immunoproliferative immunoglobulin disorders By infection KSHV (Primary effusion) · EBV (Lymphomatoid granulomatosis, Post-transplant lymphoproliferative disorder) · HIV (AIDS-related lymphoma) · Helicobacter pylori (MALT lymphoma) T/NK T cell (lymphoma, leukemia) (most CD3, CD4, CD8) By development/ marker TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) prolymphocyte (Prolymphocytic) CD30+ (Anaplastic large cell, Lymphomatoid papulosis) By location/peripheral Cutaneous (Mycosis fungoides, Sézary's disease) · Hepatosplenic · Angioimmunoblastic · Enteropathy-associated T-cell lymphoma By infection HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) Aggressive NK-cell leukemia · Blastic NK cell lymphoma T or NK EBV (Extranodal NK-T-cell lymphoma) · Large granular lymphocytic leukemia Lymphoid+myeloid Acute biphenotypic leukaemia Lymphocytosis Lymphoproliferative disorders (X-linked lymphoproliferative disease, Autoimmune lymphoproliferative syndrome) · Leukemoid reaction · Pseudolymphoma lymphocyte navs: cells/physio, immunodeficiency/immunoproliferative immunoglobulin/neoplasia, proc

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