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Cutaneous pseudolymphoma


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1. Cutaneous T-cell pseudolymphomas
A) Primarily with stripe-like infiltration (the majority of cases)
Lymphomatoid drug eruption (most cases);
Lymphomatoid contact dermatitis;
Actinic reticuloid;
Nodular scabies (individual cases);
Idiopathic forms;
Clonal cutaneous T-cell pseudolymphomas.
B) Primarily with nodular infiltration (a small percentage
of the cases)
Drug-induced – mainly by anti-convulsive drugs
Persistent nodules after insect bites;
Nodular scabies (the majority of cases).

2. Cutaneous B-cell pseudolymphomas (with nodular infiltration)
Cutaneous lymphocytoma from Borrelia burgdorferi;
Cutaneous lymphocytoma after antigens injection;
Cutaneous lymphocytoma resulting from tattoo;
Cutaneous lymphocytoma after Herpes zoster;
Idiopathic forms;
Clonal cutaneous B-cell pseudolymphomas

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Cutaneous pseudolymphoma

  1. 1. Moderator : Dr Ram Singh Meena
  2. 2.      Cutaneous pseudolymphoma(CPL) was first described under the term sarcomatosis cutis by Kaposi in 1891. In 1923, Bilerstein coined term lymphocytoma cutis Term lymphadenosis benigna cutis was introduced by bafverstedt in 1943 In 1967, Lever introduced term pseudolymphoma of Spiegler and Fendt Subsequently,Caro and Helwig in 1969 introduced term cutaneous lymphoid hyperplasia
  3. 3.   Pseudolymphoma is process of accumulation of lymphocytes in skin in response to a variety of known and unknown stimuli It simulates lymphoma, primarily histologically but sometime clinically,which at time of diagnosis appear to have a benign biological behavior and do not satisfy criteria for malignant lymphoma
  4. 4.           Mortality/Morbidity Pseudolymphoma is not associated with mortality. Localized variants rarely result in morbidity other than minor pain or pruritus. Race Although 90% of reported patients of CPL are white In localized CPL, F:M ratio is 2:1. No significant epidemiologic data are available CTPL Age Individuals of any age may be affected, but localized, nodular CPL is MC in early life. Mean age of onset is 34 years. 2/3 of patients are younger than 40 years at time of biopsy. Borrelial pseudolymphoma is more common in children than in adults
  5. 5.   Rijlaarsdam & Willemze’s classification based on clinical and morphologicalcriteria. 1. Cutaneous T-cell pseudolymphomas             A) Primarily with stripe-like infiltration (the majority of cases) Lymphomatoid drug eruption (most cases); Lymphomatoid contact dermatitis; Actinic reticuloid; Nodular scabies (individual cases); Idiopathic forms; Clonal cutaneous T-cell pseudolymphomas. B) Primarily with nodular infiltration (a small percentage of the cases) Drug-induced – mainly by anti-convulsive drugs Persistent nodules after insect bites; Nodular scabies (the majority of cases).
  6. 6.  2. Cutaneous B-cell pseudolymphomas (with nodular infiltration)       Cutaneous lymphocytoma from Borrelia burgdorferi; Cutaneous lymphocytoma after antigens injection; Cutaneous lymphocytoma resulting from tattoo; Cutaneous lymphocytoma after Herpes zoster; Idiopathic forms; Clonal cutaneous B-cell pseudolymphomas
  7. 7. Clinicopathologic Subtype Predominant Lymphoid Subset Predominant Localization Major Associated Findings Cutaneous lymphoid hyperplasia B and T cell Reticular dermis Kimura’s disease B and T cell Subcutis Lympadenopathy Angiolymphoid hyperplasia with eosinophilia B and T cell Reticular dermis Eosinophilia Castleman disease B and T cell Subcutis Lympadenopathy, POEMS syndrome Pseudo mycosis fungoides T cell Papillary dermis & Epidermis Lymphomatoid contact dermatitis T cell Papillary dermis & Epidermis Lymphocytic infiltration of the skin (Jessner’s disease) T cell Perivascular & periadnexial dermis Contact allergen
  8. 8.   Depending on predominant cell type in infiltrate,cutaneous pseudolymphomas are divided into two major categories. 1.Mixed B and T cell pseudolymphoma. cutaneous lymphoid hyperplasia,  Kimura's disease,  angiolymphoid hyperplasia with eosinophilia,  Castleman disease   2. T cell pseudolymphoma pseudo mycosis fungoides,  lymphomatoidcontact dermatitis,  Jessner’s lymphocytic infiltration of the skin  Wood GS. Inflamatory diseases that simulate lymphomas: Cutaneous lymphomas. Ed.Wolf K, Goldsmith L, Gilchrest B, Paller A, Leffell D. In. Fitzpatrick’s Dermatology in General Medicine. 7th edition
  9. 9.      Also Known as Spiegler-Fendt sarcoid, Lymphocytoma cutis, lymphadenosis benigna cutis & cutaneous lymphoplasia World-wide distribution and affects all races and ethnic groups. Both adults and children Females >males CLH is characterized by a relatively dense lymphoid infiltrate, centered in the reticular dermis, that is usually B-cell rich and may resemble lymphoma clinically and/or histopathologically
  10. 10.          In most cases of CLH is idiopathic but in some there is an identifiable trigger. These include foreign agents such as: Tattoo dye,Insect bites,Scabies, Stings and spider bites Vaccinations Desensitisation injections Trauma Acupuncture Gold earring piercing Infections with :-Borrelia burgdorferi (Lyme disease), Varicella zoster (chickenpox) and Human immunodeficiency virus (AIDS virus). Drugs
  11. 11. Class Drugs Anticonvulsants Phenytoin, carbamazepine, phenobarbital, trimethadone, primidone, butobarbitol, methsuximide, phensuximide Amitriptyline, fluoxetine, doxepin, desipramine, lithium Chlorpromazine, thioridazine, promethazine (clonazepam, lorazepam) Antidepressants Neuroleptics Tranqulizers (anxiolitics) ACE-inhibitors β-blockers H2- blockers Calcium antagonists Antirheumatic drugs Cytostatics Antibiotics Antihistamines Antiarrhythmic drugs Diuretics Antilipemic drugs Sexual steroids Local drugs Captopril, enalapril, benazepril Atenolol, labetolol Cimetidine, ranitidine Verapamil, diltiazem Aspirin, phenacetin, D-penicillamin, allopurinol Cyclosporin, methotrexate Penicillin Diphenhydramine Procainamide Hydrochlorothiazide, Moduretic Lovastatin Estrogen, progesterone Menthol, etheric oils
  12. 12.        Clinical history should elicit information about Duration and symptomatology of lesions, Nature and pace of clinical progression, Past treatment, Local and systemic exposure to foreign antigens, Including medications and personal or family history about other lymphoproliferative disorders. It also include review of systems focusing on so called lymphoma B symptoms
  13. 13.      GPE :-with special attention to type and distribution of skin lesions and to status of peripheral lymph nodes, liver and spleen. Scanning tests such as a CBC, Routine biochemistry screening and chest radiography help to exclude extra cutaneous involvement. Computed tomography of chest, abdomen and pelvis, as well as bone marrow aspiration and biopsy. Biopsy can be performed from abnormally enlarged lymph nodes Lesional skin biopsy is an essential part of diagnostic evaluation
  14. 14.     Cutaneous lesions of CLH present most commonly as a solitary nodule or can appear as a localized array of nodules, papules and plaques. Head, neck, extremities, breast and genitalia are common predilection sites. Lesions have a doughy to firm consistency & range from red- brown to violaceous in color Lesions may be pruritic or asymptomatic
  15. 15.      HPE of CLH lesions reveals dense, nodular and diffuse lymphoid infiltrate that is concentrated in t reticular dermis. Epidermis is normal and separated from underlying infiltrate by a narrow grenz zone of uninvolved papillary dermis. Lesions of CLH include generally a mixed B and T cell lymphocytes. However, various types of histiocytes, including macrophages, dermal dentritic cells, Langerhans cells are scattered throughout infiltrate. Other cells are sometimes admixed, including plasma cells, eosinophils, mast cells, neutrophils and histiocytic giant cells. Plasma cells and eosinophils are particularly common in arthropod induced reactions
  16. 16. CPL CBCL Prominent acanthosis Top heavy infiltrate (75%) dermal infiltrate with perivascular & periappendageal preference Minimal or no acanthosis Organized immune response (e.g., follicles with germinal centers, etc.); heterogeneous cellular constituency 65% with germinal centers No or few mitoses No organized immune response cellular monomorphism often present 10%-20% with germinal centers No necrosis en masse Necrosis en masse (sometime) Multinuleated gaint cells No multinuleated gaint cells &granuloma Lymphoid infiltrate with no apoptotic cells Lymphoid infiltrate puching borders with infiltrating borders apoptotic cells Preservation of adnexae Destruction of adnexae Vascular proliferation No vascular proliferation Stromal fibrosis Little or no stromal fibrosis Bottom-heavy infiltrate(65%) diffuse infiltrate that dissects collagen & may involve the subcutis Mitoes may be numerous
  17. 17.     Also known as drug-induced CPL or druginduced pseudolymphoma syndrome Divided in two major categories:1. Induced by anticonvulsants 2. Induced by other drugs
  18. 18.       Develops during first 2 to 8 weeks of drug intake, but can occur from 5 daysup to 5 years of phenytoin therapy Black>white patients Clinically, most patient have triad of fever, lymphadenopathy, and an erythemic eruptionin association with hepatosplenomegaly, blood eosinophilia Lymphadenopathy can localized or generalized Skin manifestations appear as single papule or widespread erythematous papules, plaques and nodules, but occasionally, lesions may be generalized. MC offenders are phenytoin,primidone,mephenytoin and trimethadione
  19. 19. erythrodermic pseudolymphoma drug-induced pseudolymphoma, secondary to anticonvulsant therapy
  20. 20.     Occur one month to one year following the administration of therapy M=F Localized papules together with single or multiple nodules and plaques, generalized papulonodular lesions and exfoliating erythrodermia resembling Sezàry’s syndrome Eg:-Neuroleptics,ACE-inhibitors,β-blockers, Antihistamines, Cytotoxic
  21. 21. Immunological function is reduced and immune control is impaired, leading to abnormal proliferation of lymphocytes, increased function of T-suppressors and hypogammaglobulinemia  Studies of these patients show 1. Relative increase in absolute number of peripheral T-lymphocytes by 85-95 % 2. Significant stimulation of drug-induced blastic tranformation of lymphocytes 3. Impaired ability of T-suppressor lymphocyte to suppress B-cell differentiation and immunoglobulin production 
  22. 22.     CBPL or CTPL can develop as a result of scabies or arthropod bite Clinically, multiple pruritic firm erythematous to red-brown papule and nodule MC on genitalia,abdomen,axillae and elbows Nodule following scabies may persist for many months after adequate anti-scabietic therapy It is thought to be due to delayed-type hypersensitivity reaction to componant of mite
  23. 23. nodular scabies
  24. 24.      It is known by its acronym APACHE – Acral Pseudolymphomatous Angiokeratoma of Children Apache etiology remains unknown howeverpossibility that it is a hypersensitivity reaction to insect bites Clinically characterized by presence of 10 to 40 violet-erythematic papules, diameter ranges from 1 to 4 mm, and which are asymptomatic, located unilaterally, generally with acral distribution Occurring more often between 2 and 13 years of age
  25. 25.   Histological studies of Apache reveal an epidermis of normal aspect and a dense welldifferentiated lymphocyte infiltrate in the dermis, amongst connective tissue structures, not affecting skin appendage. Such histopathological aspect configures lymphocyte proliferation,associate with no nuclear atypia.
  26. 26.    Cutaneous lymphoid hyperplasia related to infection with B. Burgdorferi, antibiotic therapy with cephalosporins Excision,glucocorticoids (topical, intralesional, and systemic), cryotherapy, antimalarials, minocycline and radiation therapy have all been used with various successes. Laser therapy and photodynamic therapy
  27. 27. Clinical features Kimura’s disease ALHE Sex Young adult male predominance Middle-aged female Age Mean range 27-40 Mean 35 years Presentation & site as solitary or multiple nodules up to 10 cm in diameter centered in subcutis, MC involving head and neck present with smaller,more superficial intradermal papulonodules that are typically unilateral. Also involve Salivary glands & resional lymph nodes(reactive) Regional L N enlargement LN often show histological evidence of involvement Uncommon, show reactive changes only Peripheral blood eosinophilia Present in majority of cases Occurs in about 20 % of cases Course Progressive, becoming stationary after years. Recurrence is common 15%-40%, but there is no fatality.Rarely, association with a nephrotic syndrome Benign lesion which recurs in about 30%of cases. Recurrence is rare if excision is complete
  28. 28. Histological features Kimura’s disease ALHE Outline Usually non-circumscribed Often circumscribed except dermal lesions Lymphoid component Abundant lymphocytes and plasma cells; lymphoid follicles are always found Sparse to heavy infiltrate of lymphocytes & plasma cells, with or without lymphoid Follicles Eosinophils Moderate to abundant; eosinophilic abscesses Sparse to abundant; eosinophilic abscess is rare Vascular proliferation Some stromal vascularity with unremarkable endothelial cells Prominent vascular proliferation with large epitheloid/ histiocytoid endothetial cells,evidence of underlying vascular malformation may evident fibrosis Prominent Absent or limited
  29. 29. FIRST LINE  Excision,  Topical corticosteroids,  Tntralesional corticosteroids (5-40 mg/ml, monthly) SECOND LINE  Topical tacrolimus ointment,  Systemic corticosteroids (60/ 40/ 20 mg PO tapers, 5 days each),  Cyclosporine (2.5- 4mg/kg/day),  Local radiation,  Vinblastine (15 mg/week IV),  Intravenous immunoglobulins
  30. 30.     Also referred to as angiofollicular lymph node hyperplasia First described by Benjamin Castleman in 1956 follicular hyperplasia of lymph nodes with abnormally increased interfollicular vascularity Can be associated with Kaposi's sarcoma (KS), non-Hodgkin's lymphoma, Hodgkin's lymphoma, and POEMS syndrome
  31. 31.    Unicentric and Multicentric Hyaline vascular , Plasmacytic and Mixed cellularity variety based on histopathology HIV associated
  32. 32.       More common Presents as slow growing solitary mass typically located in the mediastinium or mesenteries. No constitutional sm-s Not associated with progression to malignancy Treated by surgical resection with excellent results Histologicaly Unicentric CD is of hyaline vascular variety
  33. 33.        Median age 50-60’s ( younger if HIV+) Widespread lymphadenopathy Hepatosplenomegaly Can present with systemic sm-s: fatigue, fever, wt loss, night sweats (overproduction of IL-6). Severe peripheral edema, anemia, hypoalbumenia, peripheral neuropathy Also can be associated with:-autoimmune hemolytic anemia,multiple myeloma, amyloidoisis,Pemphigus & POEMS syndrome Diagnosis by biopsy: Histologicaly usually of the plasmacytic type or mixed cellularity variety
  34. 34.     More likely to be associated with Multicentric Castleman’s Disease More likely to be caused by HHV8 Associated with poor prognosis and progression to malignancy Initiation of HAART may lead to fulminant multicentric CD
  35. 35.     Kaposi's sarcoma (up to 70% in HIV+/HHV+) Non-Hodgkin's lymphoma (15-20% of pt) Hodgkin's lymphoma (both MCD & UCD) POEMS syndrome
  36. 36.        Steroids (15-20% eff, not in HIV+) IV Ig Antivirals (acylovir/gancyclovir/foscarnet) in HIVand HHV8 + population Rituximab (complete remission in few cases) CHOP or CVAD (90% eff) Anti-IL6 or anti-IL6 receptor antibody. Thalidomide (anecdotal)
  37. 37.      Eruptions mimicking mycosis fungoides occur typically in adults. Both genders can be affected. Pseudo T cell lymphomas may arise spontaneously or may occur in association with B cell chronic lymphocytic leukemia Also associated with ingestions of various drugs, including hydantoins, carbamazepine and antihistamines. The lesions present clinically as one or a few plaques on the trunk or extremities.
  38. 38. Histopathologically, there is a papillary dermal, band-like infiltrate containing mostly atypical lymphocytes with clefted and cerebriform nuclei.  Compared with mycosis fungoides,epidermotropism is typically far less prominent and Pautrier’s microabscess-like aggregates are rare.  Most cases contain polyclonal T cells In the differential  Lichenoid drug eruptions,  Lymphomatoid contact dermatitis,  Chronic radiodermatitis,  Secondery syphilis 
  39. 39.       First line of therapy Drug discontinuation Treatment of underlying disorder when an associated specific disease is detected Excision for isolated lesions, Topical and systemic corticosteroids, Ultraviolet B phototherapy and PUVA therapies
  40. 40.      LCD is a chronic and persistent allergic contact dermatitis Lymphomatoid contact dermatitis was described originally in four patients with persistent allergic contact dermatitis proven by patch testing Responsible agents include gold, nickel and paraphenylenediamine. Characterizedby generalized pruritic red, scaly papules and plaques Histopathologically, superficial lymphocytic dermatitis that contains foci of spongiosis simulating appearance of cutaneous T cell lymphomas
  41. 41.      Frequently there is edema in papillary dermis in lymphomatoid contact dermatitis, this finding is usually absent in mycosis fungoides Avoidance of the responsible allergic agents leads to eventual resolution of condition. A search for offending agent via patch testing Therapy firstly Elimination of a suspected allergic agent, later topical corticosteroids, pimecrolimus and tacrolimus ointments
  42. 42.   Jessner lymphocytic infiltrate commonly present with asymptomatic, nonscaly, erythematous papules or plaques predominantly on face and neck,upper trunk or arms of several months duration Majority of cases occur in middle aged adults
  43. 43.     Histologically ,epidermis usually is normal In dermis, a moderately dense superficial and deep perivascular lymphocytic infiltrate.Lymphocytic infiltrate may also be perifollicular or may extend into subcutis. Higher magnification reveals a predominance of small mature lymphocytes. Large lymphoid cells, plasma cells, or plasmacytoid monocytes may occasionally be present and eosinophils and neutrophils are absent. Differential diagnosis:- Polymorphous light eruption, Discoid lupus erythematosus, Welldifferentiated lymphocytic lymphoma & Lymphocytoma cutis