Primary cutaneous follicle centre lymphoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Soroush Seifirad, M.D.[3]

Primary cutaneous follicle centre lymphoma is the most common type of primary cutaneous B-cell lymphoma. Primary cutaneous follicle centre lymphoma (PCFCL) can be defined as neoplastic proliferation of the follicle germinal center cells limited to the skin. This is a tumor of neoplastic follicle centre cells, including centrocytes and variable numbers of centroblasts, with a follicular and diffuse growth pattern that generally presents on the head or trunk.Based on the growth pattern, primary cutaneous follicle centre lymphoma may be classified into follicular, diffuse, and mixed pattern. Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8. On gross pathology,solitary or grouped erythematous papules, plaques and tumor lesions, mostly non-ulcerated are characteristic findings of primary cutaneous follicle centre lymphoma. On microscopic histopathological analysis, centroblasts (large noncleaved cells), centrocytes (small and large cleaved cells), and reactive T cells are characteristic findings of primary cutaneous follicle centre lymphoma.There are no established causes for primary cutaneous follicle centre lymphoma. Primary cutaneous follicle centre lymphoma must be differentiated from other diseases such as eczema, psoriasis, and cutaneous T cell lymphoma. The incidence of primary cutaneous follicle centre lymphoma increases with age; the median age at diagnosis is 51 years. Males are more commonly affected with primary cutaneous follicle centre lymphoma than females. There are no established risk factors for primary cutaneous follicle centre lymphoma. According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for primary cutaneous follicle centre lymphoma.Prognosis is generally excellent, and the 5-year survival rate of patients with primary cutaneous follicle centre lymphoma is approximately 97%. The staging of primary cutaneous follicle centre lymphoma is based on the International Society for Cutaneous Lymphomas (ISCL) / EORTC proposal on TNM classification of cutaneous lymphoma other than mycosis fungoides / sezary syndrome.The most common symptoms of primary cutaneous follicle centre lymphoma include fever, fatigue, weight loss, skin rash, night sweats, skin rash, chest pain, abdominal pain, bone pain, and painless swelling in the neck, axilla, groin, thorax, and abdomen.^[1] Common physical examination findings of primary cutaneous follicle centre lymphoma include fever, rash, ulcer, firm erythematous or violaceous plaques, nodules, or tumors of varying sizes, chest tenderness, abdomen tenderness, bone tenderness, peripheral lymphadenopathy, and central lymphadenopathy.^[1]Laboratory tests for primary cutaneous follicle centre lymphoma include complete blood count (CBC), blood chemistry studies, cytogenetic analysis, flow cytometry, immunohistochemistry, and immunophenotyping. Lymph node biopsy is diagnostic of primary cutaneous follicle centre lymphoma. CT scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma. MRI scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma. PET scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma. Other diagnostic studies for primary cutaneous follicle centre lymphoma include laparoscopy, laparotomy, bone marrow aspiration, and bone marrow biopsy. The predominant therapy for primary cutaneous follicle centre lymphoma is radiotherapy. Adjunctive chemotherapy may be required. Surgery is not the first-line treatment option for patients with primary cutaneous follicle centre lymphoma. Surgery is usually reserved for patients with localized disease.

Primary cutaneous follicle center lymphoma is a type of lymphoma. It was recognized as a distinct disease entity in the 2008 WHO classification. PCFCL had been previously conceived as a variant of follicular lymphoma (FL).

Based on the growth pattern, primary cutaneous follicle centre lymphoma may be classified into follicular, diffuse, and mixed pattern.

Primary cutaneous follicle centre lymphoma is a tumor of neoplastic follicle centre cells, including centrocytes and variable numbers of centroblasts, with a follicular and diffuse growth pattern that generally presents on the head or trunk.^[1]Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include C-REL and BCL-2 genes. Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8. On gross pathology,solitary or grouped erythematous papules, plaques and tumor lesions, mostly non-ulcerated are characteristic findings of primary cutaneous follicle centre lymphoma. On microscopic histopathological analysis, centroblasts (large noncleaved cells), centrocytes (small and large cleaved cells), and reactive T cells are characteristic findings of primary cutaneous follicle centre lymphoma.

There are no established causes for primary cutaneous follicle centre lymphoma.

Primary cutaneous follicle centre lymphoma must be differentiated from other diseases such as eczema, psoriasis, and cutaneous T cell lymphoma.

The incidence of primary cutaneous follicle centre lymphoma increases with age; the median age at diagnosis is 51 years. Males are more commonly affected with primary cutaneous follicle centre lymphoma than females.

There are no established risk factors for primary cutaneous follicle centre lymphoma.

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for primary cutaneous follicle centre lymphoma.^[2]

Prognosis is generally excellent, and the 5-year survival rate of patients with primary cutaneous follicle centre lymphoma is approximately 97%.

Biopsy is the gold standard test for the diagnosis of primary cutaneous follicle centre lymphoma. Lymph node biopsy is diagnostic of primary cutaneous follicle centre lymphoma. The staging of primary cutaneous follicle centre lymphoma is based on the International Society for Cutaneous Lymphomas (ISCL) / EORTC proposal on TNM classification of cutaneous lymphoma other than mycosis fungoides / sezary syndrome

The most common symptoms of primary cutaneous follicle centre lymphoma include fever, fatigue, weight loss, skin rash, night sweats, skin rash, chest pain, abdominal pain, bone pain, and painless swelling in the neck, axilla, groin, thorax, and abdomen.

Common physical examination findings of primary cutaneous follicle centre lymphoma include fever, rash, ulcer, firm erythematous or violaceous plaques, nodules, or tumors of varying sizes, chest tenderness, abdomen tenderness, bone tenderness, peripheral lymphadenopathy, and central lymphadenopathy.

Laboratory tests for primary cutaneous follicle centre lymphoma include complete blood count (CBC), blood chemistry studies, cytogenetic analysis, flow cytometry, immunohistochemistry, and immunophenotyping.

There are no ECG findings associated with primary cutaneous follicle centre lymphoma.

There are no x-ray findings associated with primary cutaneous follicle centre lymphoma.

There are no echocardiography/ultrasound findings associated with primary cutaneous follicle centre lymphoma.

CT scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma.

MRI scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma.

PET scan may be helpful in the diagnosis of primary cutaneous follicle centre lymphoma.

Other diagnostic studies for primary cutaneous follicle centre lymphoma include laparoscopy, laparotomy, bone marrow aspiration, and bone marrow biopsy.

The predominant therapy for primary cutaneous follicle centre lymphoma is radiotherapy. Adjunctive chemotherapy may be required.

Surgery is not the first-line treatment option for patients with primary cutaneous follicle centre lymphoma. Surgery is usually reserved for patients with localized disease.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2] Sowminya Arikapudi, M.B,B.S. [3]

Primary cutaneous follicle center lymphoma is a type of lymphoma. It was recognized as a distinct disease entity in the 2008 WHO classification. PCFCL had been previously conceived as a variant of follicular lymphoma (FL).

Primary cutaneous follicle center lymphoma is a type of lymphoma. It was recognized as a distinct disease entity in the 2008 WHO classification. PCFCL had been previously conceived as a variant of follicular lymphoma (FL).^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Soroush Seifirad, M.D.[3]

Based on the growth pattern, primary cutaneous follicle centre lymphoma may be classified into follicular, diffuse, and mixed pattern.^[1]

Based on the growth pattern, primary cutaneous follicle centre lymphoma may be classified into:^[1]

• Follicular
• Diffuse
• Mixed

• Non-Hodgkin lymphoma may be classified according to updated WHO classification into 2 groups:^[2][3]

• B-cell neoplasms
• T-cell and putative NK-cell neoplasms

Updated WHO classification of Non-Hodgkin lymphoma

B-cell neoplasms	T-cell and putative NK-cell neoplasms
Precursor B-cell neoplasm	Precursor T-cell neoplasm
Precursor B-acute lymphoblastic leukemia / lymphoblastic lymphoma (LBL)	Precursor T-acute lymphoblastic leukemia / lymphoblastic lymphoma (LBL)
Mature B-cell neoplasms	Peripheral T-cell and NK-cell neoplasms
Chronic lymphocytic leukemia / small lymphocytic lymphoma	T-cell prolymphocytic leukemia
Monoclonal B-cell lymphocytosis	T-cell granular lymphocytic leukemia
B-cell prolymphocytic leukemia	Chronic lymphoproliferative disorder of NK cells
Splenic marginal zone lymphoma (± villous lymphocytes) Splenic B-cell lymphoma/leukemia, unclassifiable 1. Splenic diffuse red pulp small B-cell lymphoma 2. Hairy cell leukemia-variant	Aggressive NK-cell leukemia
Hairy cell leukemia	Systemic EBV positive T-cell lymphoma of childhood
Lymphoplasmacytic lymphoma Waldenström’s macroglubulinemia	Hydroa vacciniforme like lymphoproliferative disorder
Monoclonal gammopathy of undetermined significance (MGUS), IgM IgG/A	Adult T-cell leukemia/lymphoma
Heavy chain disease µ heavy-chain disease ɣ heavy-chain disease α heavy-chain disease	Extranodal T/NK-cell lymphoma, nasal type
Plasma cell myeloma (multiple myloma)	Enteropathy associated intestinal T-cell lymphoma
Solitary plasmacytoma of bone	Monomorphic epitheliotropic intestinal T-cell lymphoma
Extraosseous plasmacytoma	Indolent T-cell lymphoproliferative disorder of the GI tract
Monoclonal immunoglobulin deposition diseases	Hepatosplenic T-cell lymphoma
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)	Subcutaneous panniculitis-like T-cell lymphoma
Nodal marginal zone B-cell lymphoma (± monocytoid B-cells) pediatric Nodal marginal zone B-cell lymphoma	Mycosis fungoides
Follicular lymphoma In situ follicular neoplasia Duodenal-type follicular lymphoma Pediatric-type follicular lymphoma	Sézary syndrome
Large B-cell lymphoma with IRF4 rearrangement	Primary cutaneous CD30 T-cell lymphoproliferative disorders Lymphomatoid papulosis Primary cutaneous anaplastic large cell lymphoma
Primary cutaneous follicle center lymphoma	Primary cutaneous gamma delta T-cell lymphoma Primary cutaneous CD8 aggressive epidermotropic cytotoxic T-cell lymphoma Primary cutaneous acral CD8 T-cell lymphoma Primary cutaneous CD4 small/medium T-cell lymphoproliferative disorder
Mantle cell lymphoma In situ mantle cell neoplasia	Peripheral T-cell lymphoma, NOS * Peripheral T-cell lymphoma, not otherwise characterized
Diffuse large B-cell lymphoma (DLBCL), NOS Germinal center B-cell type Activated B-cell type Primary DLBCL of the central nervous system (CNS) Primary cutaneous DLBCL, leg type DLBCL associated with chronic inflammation HHV81 DLBCL, NOS	Angioimmunoblastic T-cell lymphoma
T-cell/histiocyte-rich large B-cell lymphoma	Follicular T-cell lymphoma
EBV1 DLBCL, NOS EBV1 mucocutaneous ulcer	Nodal peripheral T-cell lymphoma with TFH phenotype
Lymphomatoid granulomatosis	Anaplastic large cell lymphoma ALK positive ALK negitive
Primary mediastinal (thymic) large B-cell lymphoma	Breast implant associated anaplastic large-cell lymphoma
Intravascular large B-cell lymphoma
ALK1 large B-cell lymphoma
Plasmablastic lymphoma
Primary effusion lymphoma
Burkitt lymphoma Burkitt-like lymphoma with 11q aberration
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements High-grade B-cell lymphoma, NOS*
B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma

• Non-Hodgkin lymphoma may be classified based on rate of growth into 2 groups:^[4]

• Low-grade or Indolent lymphoma
• High-grade or Aggressive lymphoma

Non-Hodgkin lymphoma classification

Grade	Description
Low-grade or Indolent lymphoma	Tend to grow very slowly Tend to be widespread by the time they are diagnosed Often involving the bone marrow and spleen Often treated only when symptoms appear Can shrink or seem to disappear with treatment, but they tend to come back Can change into more aggressive lymphomas Have a fairly good prognosis
High-grade or Aggressive lymphoma	Grow quickly and tend to spread to lymph nodes or other organs throughout the body Cause symptoms and need treatment right away Can frequently be successfully treated with intensive chemotherapy treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Primary cutaneous follicle centre lymphoma is a tumor of neoplastic follicle centre cells, including centrocytes and variable numbers of centroblasts, with a follicular and diffuse growth pattern that generally presents on the head or trunk.^[1]Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include C-REL and BCL-2 genes. Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8. On gross pathology,solitary or grouped erythematous papules, plaques and tumor lesions, mostly non-ulcerated are characteristic findings of primary cutaneous follicle centre lymphoma. On microscopic histopathological analysis, centroblasts (large noncleaved cells), centrocytes (small and large cleaved cells), and reactive T cells are characteristic findings of primary cutaneous follicle centre lymphoma.

Primary cutaneous follicle centre lymphoma is a tumor of neoplastic follicle centre cells, including centrocytes and variable numbers of centroblasts, with a follicular and diffuse growth pattern that generally presents on the head or trunk.^[1]Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include C-REL and BCL-2 genes.^[1] Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8. On gross pathology,solitary or grouped erythematous papules, plaques and tumor lesions, mostly non-ulcerated are characteristic findings of primary cutaneous follicle centre lymphoma. On microscopic histopathological analysis, centroblasts (large noncleaved cells), centrocytes (small and large cleaved cells), and reactive T cells are characteristic findings of primary cutaneous follicle centre lymphoma.^[2]

Primary cutaneous follicle centre lymphoma (PCFCL) is characterized by a proliferation of follicle center cells (centrocytes and centroblasts) with a follicular, follicular and diffuse, or diffuse growth pattern.^[3]

Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include:^[1]

• Amplification of C-REL gene
• BCL-2 rearrangements

Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with:^[2]

• Borrelia burgdorferi
• Hepatitis C
• Human herpesvirus 8

On gross pathology, solitary or grouped erythematous papules, plaques and tumor lesions, mostly non-ulcerated are characteristic findings of primary cutaneous follicle centre lymphoma.^[2]

On microscopic histopathological analysis, centroblasts (large noncleaved cells), centrocytes (small and large cleaved cells), and reactive T cells are characteristic findings of primary cutaneous follicle centre lymphoma.^[2]

• Histopathological appearance of primary cutaneous follicle centre lymphoma include:^[4]

• Epidemis

• Superficially regular and preserved

• Deep dermis

• Abundant lymphocytic infiltrate with the formation of follicular germinal center and the surrounding ‘mantle zone’
• The infiltrate was composed of atypical, medium-sized and focally large lymphatic cells

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

There are no established causes for primary cutaneous follicle centre lymphoma.

There are no established causes for primary cutaneous follicle centre lymphoma.

• Unlike FL, PCFCL is not typically associated with t(14;18) translocation, although the presence of that translocation does not exclude PCFCL. It is usually not associated with overexpressed Bcl-2.^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2], Sogand Goudarzi, MD [3], Sowminya Arikapudi, M.B,B.S. [4]

Primary cutaneous follicle centre lymphoma a must be differentiated from other diseases such as eczema and psoriasis.

• Primary cutaneous follicle centre lymphoma must be differentiated from mycosis fungoides or any other diseases with cutaneous patch or plaque that not respond to first- and second-line treatment such as:^{[1][2][3][4][5][6]}
  • Sezaruy syndrome
    • Sezaruy syndrome(SS) is more symptoI contrast to patch or plaque mycosis fungoides, SS is much more symptomatic. Sezary syndrome patients tend to present with diffuse skin involvement,not like mycosis fungoides usually evolve through patches and plaques to erythroderma ^[7]
    • In Sezary syndrome infiltration of skin is generally much less dense than plaque in mycosis fungoides (MF)
  • Eczema
  • Adult T cell leukemia/lymphoma
  • Psoriasis
  • Pityriasis rubra pilaris
  • dermatitis
  • Hypereosinophilic syndrome
  • Adult T-cell leukemia
  • Atopic dermatitis
  • Contact dermatitis ( Allergic, irritant)
  • Chronic actinic dermatitis
  • Scabies
  • Subcutaneous panniculitis like T cell lymphoma (SPTCL)
  • Drug eruption
  • Graft versus host disease
  • Lichen planus
  • Pediatric atopic dermatitis
  • Tinea corporis
  • Primary cutaneous anaplastic large cell lymphoma (ALCL)
  • Cutaneous gamma/delta T cell lymphoma (G/D TCL)

Disease	Rash Characteristics	Signs and Symptoms	Associated Conditions
Primary Cutaneous Follicle Centre lymphoma	Firm erythematous or violaceous plaques, nodules, or tumors of varying sizes May be ulcerated	Fever Rash, ulcer, firm erythematous or violaceous plaques, nodules, or tumors of varying sizes Fatigue Weight loss Night sweats Chest pain Abdominal pain Bone pain Painless swelling in the neck, axilla, groin, thorax, and abdomen (lymphadenopathy)	Lyme disease (Borrelia burgdorferi) Hepatitis C Human herpes virus 8 (HHV8)
Cutaneous T cell lymphoma/Mycosis fungoides[8]	Premycotic phase: A scaly, red rash in areas of the body that usually are not exposed to the sun. This rash does not cause symptoms and may last for months or years. Patch phase: Thin, reddened, eczema -like rash. Plaque phase: Small raised bumps (papules) or hardened lesions on the skin, which may be reddened. Tumor phase: Tumors form on the skin. These tumors may develop ulcers and the skin may get infected.	Epidermal atrophy or poikiloderma Generalized itching (pruritus) Pain in the affected area of the skin. Insomnia Red (erythematous) patches scattered over the skin of the trunk and the extremities Tumor-like lobulated outgrowths form on the skin in the latter part of the disease Weight loss Lymphadenopathy Malaise and fatigue Anemia May progress to Sezary syndrome (Skin involvement plus hematogenous dissemination)	Sezary syndrome
Pityriasis rosea[9]	Pink or salmon in colour, which may be scaly, termed as “herald patch” Oval in shape Long axis oriented along the clevage lines Distributed on the trunk and proximal extremities Squamous marginal collarette and a “fir-tree” or “Christmas tree” distribution on the posterior trunk Develops after viral infection Resolves spontaneously after 6-8 weeks	Preceded by a prodrome of: Sore throat Gastrointestinal disturbance Fever Arthralgia	Infection by any of the following:[10] HHV-6 HHV-7 HHV-8
Pityriasis lichenoides chronica	Recurrent lesions are usually less evenly scattered than psoriasis Brownish red or orange-brown color Lesions are capped by a single detachable opaque mica-like scale Often leave hypopigmented macules	High fever Malaise Myalgias Skin burning Pruritis	Infection by any of the following:[11] Epstein-Barr virus (EBV) Toxoplasma gondii Human immunodeficiency virus (HIV)
Nummular dermatitis[12]	Multiple coinshaped eczematous lesions Commonly affecting the extremities (lower>upper) and trunk May ooze fluid and become dry and crusty	Often appears after a skin injury, such as a burn, abrasion (from friction), or insect bite Lesions commonly relapse after occasional remission or may persist for long periods Pruritis	Associated with: Dry skin Emotional stress Allergens(rubber chemicals, formaldehyde, neomycin, chrome, mercury and nickel) Staphylococcus infection Seasonal variation Alcohol Drugs Atopy
Secondary syphilis[13]	Round coppery red color lesions on palms and soles Papules with collarette of scales	Fever Generalized lymphadenopathy Sore throat Patchy hair loss Headaches Weight loss Myalgia Fatigue	Associated with: Condylomata lata Corona verinata Positive VDRL test
Bowen’s disease[14]	Erythematous little scaly plaque, which enlarges over time in an erratic manner Scale is usually yellow or white and it is easily detachable without producing any bleeding Well defined margins	Pruritis Pain Bleeding lesions	Associated with:[15] Erythroplasia of Queyrat (Bowen’s disease of the penis) Squamous cell carcinoma Solar radiation and ultraviolet (UV) exposure Radiotherapy Immunosuppression Arsenic exposure Human papilloma virus (HPV) type 16 Merkel cell polyomavirus Sjögren’s syndrome
Exanthematous pustulosis[16]	Numerous small, primarily non-follicular, sterile pustules, arising within large areas of edematous erythema	Fever Leukocytosis Intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils	Associated with:[17] Antibiotics (penicillins, sulfonamides, tetracyclines) Carbamazepine Calcium channel blockers(Diltiazem) Hydroxychloroquine
Hypertrophic lichen planus[18]	Classically involves shin and ankles and is characterized by hyperkeratotic plaques and nodules covered by a scale Lesions may transform into hyperkeratotic thickened elevated purplish or reddish plaques and nodules	Chronic pruritis Scaling May be asymptomatic	Associated with Hepatitis C virus infection[19]
Sneddon–Wilkinson disease[20]	Flaccid pustules that are often generalized and have a tendency to involve the flexural areas Have an annular configuration	Pruritis May be asymptomatic	Associated with: Monoclonal gammopathy, usually an IgA paraproteinemia[21] Crohn’s disease[22] Osteomyelitis Adalimumab[23]
Small plaque parapsoriasis[24]	Erythematous plaques which are covered with fine scale. May present with elongated, finger-like patches symmetrically distributed on the flanks, also known as digitate dermatosis	Lesions may be asymptomatic May be mildly pruritic May fade or disappear after sun exposure during the summer season, but typically recur during the winter	May progress to mycosis fungoides[25]
Intertrigo[26]	Red and fleshy looking lesion in skin folds Itching Oozing May be sore	Pruritis Musty odor	Associated with: Infections (Fungal, bacterial, viral) Allergies Diabetes Obesity
Langerhans cell histiocytosis[27]	Scaling and crusting of the scalp	Pathological fractures[28] Visceromegaly (hepatomegaly, spleenomegaly) Chronic cough Dyspnea[29] Lymphadenopathy	Associated with: Diabetes insipidus[30] Pancytopenia
Tinea manuum/pedum/capitis[31]	Scaling, flaking, and sometimes blistering of the affected areas Hair loss with a black dot on scalp in case of tinea capitis	Pruritis KOH preparation of the lesions confirms fungal infection	Associated with: Diabetes Immunosupression Intimate contact with infected person May lead to asthma exacerbation
Seborrheic dermatitis [32][33]	Papulosquamous, scaly, flaky, itchy, and red rash found particularly at sebaceous gland-rich areas of the body		Associated with: AIDS Stress Fungal infection Fatigue Sleep deprivation Change of season Parkinson’s disease Biotin deficiency

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Soroush Seifirad, M.D.[3]

The incidence of primary cutaneous follicle centre lymphoma increases with age; the median age at diagnosis is 51 years. Males are more commonly affected with primary cutaneous follicle centre lymphoma than females.^[1]

According to a large population-based study focused on cutaneous lymphomas (CL) in the United States by Bradford et al. on 3884 Cutaneous lymphomas 9CLs) diagnosed during 2001-2005. Cutaneous T-cell lymphomas (CTCLs) accounted for 71% (age-adjusted incidence rate [IR] = 7.7/1 000 000 person-years), whereas cutaneous B-cell lymphomas(CBCLs) accounted for 29% (IR = 3.1/1 000 000 person-years).^[2]

• Over the past 25 years, the CL incidence rate increased from 5.0/1 000 000 person-years during 1980-1982 to 14.3 during 2001-2003.
• During 2004-2005, the CL IR was 12.7. This recent apparent change could be incomplete case ascertainment or potential levelling off of incidence rates.
• CLs rates vary markedly by race and sex, supporting the notion that they represent distinct disease entities.

• There is no prevalence report primary cutaneous follicle centre lymphoma.
• Primary cutaneous follicle center lymphoma is the most common primary cutaneous B-cell lymphoma.
• It accounts for approximately 10% to 20% of all cutaneous lymphomas and comprises about 50% of primary cutaneous B-cell lymphomas.

• The case-fatality rate/mortality rate of primary cutaneous follicle centre lymphoma is quite low.
• Spread from the skin is unusual, and the prognosis is excellent with a 5-year survival of over 97%.
• The International Extranodal Lymphoma Study Group identified elevated LDH, more than two skin lesions, and nodular lesions as three prognostic factors, that are used to assess a cutaneous lymphoma international prognostic index (CLIPI), which is prognostic of disease-free status.

• The incidence of primary cutaneous follicle centre lymphoma increases with age; the median age at diagnosis is 51 years.^[1]

• Most commonly, patients are white men, 50 to 60 years old, although younger patients and women may also develop this lymphoma.

• Primary cutaneous follicle centre lymphoma usually affects individuals of the blacks and non-Hispanic whites followed by Hispanic whites and Asian/Pacific Islanders . Whites of European descent individuals are less likely to develop primary cutaneous follicle centre lymphoma.
• According to Bradford et al. CL incidence rate were highest among blacks and non-Hispanic whites (both 11.5/1 000 000 person-years), followed by Hispanic whites (7.9) and Asian/Pacific Islanders (7.1). The CTCL IR was highest among blacks (10.0/1 000 000 person-years), whereas the CBCL IR was highest among non-Hispanic whites (3.5).^[2]

Males are more commonly affected with primary cutaneous follicle centre lymphoma than females.^[1]

According to Bradford et al. also, males had a statistically significant higher incidence of CL than females (14.0 vs 8.2/1 000 000 person-years, respectively; male-female IR ratio [M/F IRR] = 1.72; P < .001).^[2]

• Theoretically, and according to some studies primary cutaneous follicle centre lymphoma cases are more reported in areas of increased prevalence of the following pathogenes:
  • Borrelia burgdorferi
  • Hepatitis C
  • Human herpesvirus 8
    

• Specifically, the region of southeast Asian countries have a presumable high incidence of cutaneous T cell Lymphoma(CTCL), in particular, Epstein-Baar virus-associated natural killer/T-cell lymphomas, while Cutaneous B cell lymphomas (CBCL) are very uncommon.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

There are no established risk factors for primary cutaneous follicle centre lymphoma. Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include C-REL and BCL-2 genes. Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8.

There are no established risk factors for primary cutaneous follicle centre lymphoma.

Genes involved in the pathogenesis of primary cutaneous follicle centre lymphoma include C-REL and BCL-2 genes. Primary cutaneous follicle centre lymphoma (PCFCL) may be associated with borrelia burgdorferi, hepatitis C, and human herpesvirus 8.^{[1] [2]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for primary cutaneous follicle centre lymphoma.^[1]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for primary cutaneous follicle centre lymphoma.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Prognosis is generally excellent, and the 5-year survival rate of patients with primary cutaneous follicle centre lymphoma is approximately 97%.

• Primary cutaneous follicle centre lymphoma shows a predilection for the scalp, forehead, and trunk and dissemination to extracutaneous sites rarely occurs.^[1]
• Cutaneous relapses noted in ~30% of patients.^[2]
• Recurrences usually proximate to the initial site of the tumor.
• Untreated skin lesions increase in size, rarely metastases to other sites.

• Transformation of systemic follicular lymphoma (FL) into aggressive non-Hodgkin’s lymphoma is associated with poor prognosis and has been reported with a wide range of frequency (range between 10%–70%).
• While the annual risk of transformation of systemic follicular lymphoma (FL) is 3%.

• Prognosis is generally excellent, and the 5-year survival rate of patients with primary cutaneous follicle centre lymphoma is approximately 97%.
• The International Extranodal Lymphoma Study Group identified three prognostic factors, that are used to assess a cutaneous lymphoma international prognostic index (CLIPI), which is prognostic of disease-free status.^[3]

• Elevated LDH
• More than two skin lesions
• Nodular lesions

• If left untreated, the lesions typically increase in size over years.
• In approximately 10 percent of patients may disseminate to extracutaneous sites.
  

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