Cutaneous pseudolymphoma (CPL) is a benign process that simulates lymphoma and can present in various forms, classified into cutaneous T-cell and B-cell pseudolymphomas based on histological patterns. The document discusses historical aspects, definitions, etiological factors, clinical features, and the pathogenesis of CPL, including specific drug-related eruptions and infections as causes. Management strategies vary based on the type of pseudolymphoma, with many cases resolving after discontinuing the inciting agent or requiring other treatments.

1. CUTANEOUS
PSEUDOLYMPHOMA
PRESENTER : DR. SHEIKH
TOUSIF REZA
MODERATOR: DR.
JAYAPRAKASH SHETTY K

2. HISTORICAL ASPECTS
 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. DEFINITION
 A process that simulates lymphoma, primarily
histologically but sometimes clinically, which at the time
of diagnosis appears to have a benign biologic behaviour
and does not satisfy criteria for malignant lymphoma.

4.  This is a heterogeneous group of dermatoses with clinical
manifestations varying from tumor-like nodes to flat cell
infiltrates.
 It does not refer a specific disease
 It does not imply anything about the cause
 But , it implies a process of accumulation of lymphocytes in
the skin in response to variety of known and unknown stimuli.

5. CLASSIFICATION OF CUTANEOUS PSEUDOLYMPHOMA
 Cutaneous T-cell pseudolymphoma
i) Band like pattern
ii) Nodular pattern
 Cutaneous B cell pseudolymphoma
i) Nodular pattern

6.  Cutaneous T-cell pseudolymphoma(Band pattern)
i) Idiopathic
ii) Lymphomatoid drug eruptions (mc)
iii) Lymphomatoid contact dermatitis
iv) Nodular scabies
v) Actinic retinioid
vi) Lymphomatoid papulosis (type B)
vii) Clonal

7.  Cutaneous T-cell pseudolymphoma(Nodular pattern)
i) Anticonvulsant induced pseudolymphoma
syndrome
ii) Persistent nodular arthropod bite reaction
iii) Nodular scabies (mc)
iv) Acral pseudolymphomatous angiokeratoma
v) Lymphomatoid papulosis (type A)

8.  Cutaneous B-cell pseudolymphoma(Nodular pattern)
i) Idiopathic lymphocytoma cutis
ii) Borrelial lymphocytoma cutis
iii) Tatto induced lymphocytoma cutis
iv) Post-herpes zoster scar lymphocytoma cutis
v) Lymphocytoma cutis caused by antigen
injections/acupuncture
vi) Persistent nodular arthropod-bite reactions
vii) Lymphomatoid drug eruptions
viii) Acral pseudolymphomatous angiokeratoma
ix) Clonal

9. CAUSES OF CUTANEOUS PSEUDOLYMPHOMA
1. Drugs
2. Foreign agents: tattoo dyes, insect bites, scabies,
injection of arthropod venom, vaccinations, contactants,
trauma, acupuncture
3. Infections: B. burgdorferi, varicella zoster, HIV
4. Photosensitivity
5. Idiopathic

10. LYMPHAMATOID DRUG ERUPTIONS
 It can be divided into 2 categories
a) Anticonvulsant induced pseudolymphoma syndrome
b) Cutaneous lymphoma induced by drug other than
anticonvulsants.

12. LYMPHAMATOID DRUG ERUPTIONS
 within 2 to 8 weeks
 Clinical triad
 Eosinophilia
 Hepatosplenomegaly
 Lesions disappear after
discontinuing the drug.
Fever
Lymphadenopathy
Erythematous eruptions
Widespread
erythematous
papules,plaques or
nodules

13. PATHOGENESIS OF LYMPHOMATOID DRUG
ERUPTIONS
 Significant stimulation of drug induced blastic
transformation of lymphocytes
 Impaired ability of T-suppressor lymphocytes to suppress
B-cell differentiation and immunoglobulin production
 Increase in the relative and absolute number of
peripheral T lymphocytes

14.  Prototypic reaction pattern resembles mycosis fungoides
but also lymphocytoma cutis and follicular mucinosis.
 In anti-convulsant induced pseudolymphoma syndrome,
the lymph node may show focal necrosis, eosinophilic
and histiocyte infiltration.
•Acanthosis
•Minimal spongiosis
•Epidermotropic
lymphocytes

15. LYMPHOMATOID CONTACT DERMATITIS
 Pruritic , generalized, discrete and confluent, erythematous,
scaly papules, and plaques.
 Similar histologic features of Mycosis fungoides.
 Etiologic elements: gold, nickel and
paraphenylenediamine
•Superficial lymphocytic
dermatitis
•Spongiosis
•Edema in papillary dermis

16. PERSISTENT NODULAR ARTHROPOD-BITE
REACTIONS AND NODULAR SCABIES.
 Multiple pruritic firm erythematous to red-brown papules
and nodules
 Elbows, abdomen, genitalia, and axillae.
 Pathogenesis thought to be a delayed-type
hypersensitivity reaction

17. •Acanthosis
•Perivascular and
interstitial infiltrate

18. ACRAL PSEUDOLYMPHOMATOUS ANGIOKERATOMA
 2 to 16 yrs
 Unilateral eruption of 1 to 5 mm, red or violaceous,
discrete, irregularly shaped, angiomatous papules with
hyperkeratotic collars present on acral regions.
 Variant of the persistent nodular arthropod reactions.
Raised , scaly,
undulating lesion

19. •Top heavy pattern
infiltrates
•Secondary follicles with
germinal centre
•Thick walled blood
vessels with plump
endothelial cells

20. ACTINIC RETICULOID
 Severe, chronic, persistent, pruritic photosensitive
dermatosis.
 Red, scaly, lichenoid, papules, plaques and nodules on
light exposed skin.
 Leonine facies with deep furrows in lichenified skin may
develop.
 Generalized lymphadenopathy

21. •Acanthosis
•Exocytosis of
lymphocytes
• multinucleated
fibroblasts
•Thick walled
blood vessels
Vertically oriented coarse collagen bu
ndles parallel to the rete ridges

22. LYMPHAMATOID PAPULOSIS
 Criteria to diagnose are:
a) Multiple ulcerative
papulonodules
b) Waxing and waning of lesions
c) Less than 3 cm during 3 months of observation.
d) Absence of lymphadenopathy and systemic involvement
 Five subtypes: A,B,C,D,E

23.  Type A: most common, wedge-shaped infiltrate
comprising large pleomorphic and anaplastic CD30
lymphocytes.The admixed inflammatory infiltrate consists
of histiocytes, neutrophils, and eosinophils

24.  Type B: Band like infiltrate

25.  Type C: CD 30+ cells with fewer inflammatory cells
CD 30+ cells > 50%

26.  Type D: prominent epidermotropism of atypical small-
and medium-sized CD8 and CD30 pleomorphic
lymphocytes.
CD 8+

27.  Type E: Angioinvasive type, thrombi, vascular invasion
and cause necrosis and ulceration.

28. JESSNER LYMPHOCYTIC INFILTRATION OF THE SKIN
• Asymptomatic,
• Non-scaly, erythematous
papules or plaques
• Predominantly on face
and neck,upper trunk or a
rms of several months
duration
•Majority of cases occur in
middle aged adults

29. Deep perivascular
infiltration, may extend to
subcutis
Normal epidermis

30. IDIOPATHIC LYMPHOCYTIC CUTIS
 Sites of invovement
 Also known as cutaneous
lymphoid hyperplasia,
pseudolymphoma of Spiegler
and Fendt, lymphodenosis
benigna adenoisis
 Both localized and generalized forms
•Face 70%
•Chest 36%
•Upper 25%
extremities
Multiple erythematous
firm papules on the tip
of the nose

31. Well defined “top-heavy” nodular infiltrate in the
upper dermis

32. BORRELIAL LYMPHOCYTOMA CUTIS
 Borrelia burgdorferi infection
 Vector : Ixodes ricinus
tick
 0.6 to 1.3% reported in lyme disease
 Predilection site : ear lobule, nipple
and areola, nose and scrotal region
Blue-red
plaque or
nodule , 1 to
5 cm

33. Thin grenz zone in upper
dermis
Dense, diffuse infiltrate of
small and large lymphocytes
admixed with occasional
histiocytes and plasma cells.

34. VACCINATION INDUCED CUTANEOUS PSEUDOLYMPHOMA
 Appear at the site of vaccination
 Reactive B-cell growth pattern with many histiocytes
 These histiocytes have granular eosinophilic to basophilic
cytoplasm representing intracellular aluminium deposits.

35. PSEUDOLYMPHOMA FOLLICULITIS
 Solitary nodule on a face
 Dense lymphocytic infiltrate
in dermis and subcutaneous
fat
 The walls of hair follicles
are enlarged and irregular
 Their epithelium is blurred
by lymphocytic infiltrates

36. KIMURA ‘S DISEASE
 Single or multiple nodules upto 10 cm in diameter
 Head and neck – most common
 Peripheral eosinophilia and regional lymphadenopathy

37. Abundant number of e
osinophils in
germinal centre
Germinal c
entre
formation i
n deeper d
ermis

38. CASTLEMAN’S DISEASE
 Also referred to as angiofollicular lymph node hyperplasia
 First described by Benjamin Castleman in 1956
Types of Castleman’s disease
 Unicentric and Multicentric
 Hyaline vascular , Plasmacytic and Mixed cellularity variety
based on histopathology
 HIV associated

39. UNICENTRIC CASTLEMAN’S DISEASE
Marked vascular
proliferation with
hyalinization
broad mantle zone consisting o
f a concentric layering of
lymphocytes resulting in an
onion-skin appearance

40. MULTICENTRIC CASTLEMAN’S DISEASE
Interfollicular region shows diffuse
plasma cell infiltration
Eosinophilic
deposits of fibrin
and immune
complexes

41. SMALL PLAQUE PSORIASIS
Small, flat, erythematous le
sions seem
indistinguishable from
those of
conventional
mycosis fungoides.

42. Superficial
infiltrate in
papillary dermis
Intradermal
lymphocytes

43. IDIOPATHIC FOLLICULAR MUCINOSIS
Slightly erythematous
patch on
the lumbal region
follicular distribution of th
e lesions

44. Dense perifollicular lymphoid infilt
rates
Hair follicle
Focal deposition
of mucin
Intraepithelial
lymphocytes

45. LUPUS ERYTHEMATOSUS
 Lupus erythematosus profundus , also referred as lupus
erythematosus panniculitis.
Dermal subcutaneous interface shows
intense inflammatory infiltrate
Adipose tissue hyalinization

46. PIGMENTED PURPURIC DERMATOSIS
Dense lymphohistiocytic
infiltrate is present in
the superficial dermis
in a band-like fashion
spongiosis
Extravasated RBCs near the
venules

47. PERNIOSIS (CHILBLAINS)
 Abnormal inflammatory response to cold
 Seen commonly in acral locations
Papillary dermal edema
Superficial and deep
perivascular
lymphocytic infiltration

48. Swollen Endothelial cells
and show infiltration
by lymphocytes
Medium-sized vessels i
nfiltrated by
lymphocytes

49. HISTOLOGIC PATTERNS OF CUTANEOUS PSEUDOLYMHOMA
 Histologic diagnosis of CPL depends on two
considerations
(1) the architectural pattern of the infiltrate and
(2) the composition and cytologic condition of the cells
that comprise the infiltrate.
 Patterns of the infiltrate in CPL: a bandlike pattern and a
nodular pattern

50. HISTOLOGIC PATTERNS OF CUTANEOUS T-CELL
PSEUDOLYMHOMA
 Mostly band like pattern similar to mycosis fungoides.
 Blurring of the dermoepidermal junction.
 variable acanthosis and minimal spongiosis.
 Epidermotropism of lymphocytes, with occasional
Pautrier microabscess like collections.

51. HISTOLOGIC FEATURES OF CUTANEOUS B-CELL
PSEUDOLYMPHOMA
 Nodular or diffuse infiltrate of lymphocytes
 Infiltrates involve the papillary dermis
 Germinal centers are divided into 2 types
a) small cell nodular form- typical germinal centre and
lacks cellular pleomorphism.
b) large cell nodular form- large pleomorphic
lymphocytes and frequent mitotic figures.

52. IMMUNOHISTOCHEMICAL STUDIES
 (1) overexpression or deletion of certain markers in
certain populations of lymphocytes,
 (2) the presence of so-called immature markers or
determinants,
 (3) the presence of antigens expressed solely by
malignant lymphoid cells

54. IMMUNOHISTOCHEMICAL FEATURES OF CUTANEOUS T-
CELL PSEUDOLYMPHOMA
 Most are CD4+ with the exception of actinic reticuloid and
HIV related cutaneous PL which are CD8+.
 Lymphomatoid papulosis show CD30+.
 In lymphomatoid papulosis, large atypical lymphocytes
are CD30+.
 Loss of pan-T-cell markers (CD2, CD3, CD5) described
in CTCL has not been reported in CTPL.
 loss of CD7, a common finding in CTCL, is rare in CTPL

55. IMMUNOHISTOCHEMICAL FEATURES OF CUTANEOUS B-
CELL PSEUDOLYMPHOMA
 Expression of polyclonal light chains i.e. mixture of kappa
and lambda in pseudolymphoma in contrast to lymphoma
in which one light chain predominates.
 MT2/CD45RA and Anti-bcl-2 protein monoclonal
antibodies are also useful markers in distinguishing
primary cutaneous follicular lymphomas from CBPL with
germinal centers.

56. CLONALITY
 “Polyclonality signifies benign, monoclonality signifies
malignant”- however is not absolute.
 Monoclonality has been demonstrated in some benign or
reactive conditions, such as Lymphomatoid papulosis,
pityriasis lichenoides et varioliformis acuta, and
cutaneous lymphoid hyperplasia.

57.  The finding of clonal T- or B-cell populations in
Cutaneous pseudolymphoma suggests that gene
rearrangement analysis cannot be used as an absolute
criterion in the differentiation between CPL and
cutaneous lymphoma.
 Presence of clonality must be interpreted in the context of
the clinicopathologic and immunohistochemical features
of cutaneous lymphoproliferative processes

58. CT-CELL PL VS C T-CELL LYMPHOMA
Features T cell psedo T cell lymphoma
Presentation Localized Generalized
Clinical course Spontaneous
remission
Progressive
Epidermotropism Mild Present
Spongisis +++++ Minimal
Pautrier microabscess -------- +++++
Lymphocytes Small/benign looking Large/ atypical
CD2,CD3,CD5 +++++ ----------
Loss of CD7 Rare Common
TCR rearrangement 10-19% 90%

59. CB-CELL PL VS C B-CELL LYMPHOMA
Cutaneous B cell psedo Cutaneous B cell lymphoma
Acanthosis ++++ Acanthosis -----
Top heavy infiltrate Bottom heavy infiltrate
Indian filing ------ Indian filing ++++
Mixed infiltrates of lymphocyte Monomorphous population
Mitoses few Mitoses ++++
65% with germinal center 10-20% with germinal center
Multinucleated giant cell++ Multinucleated giant cell --
Preservation of adnexa Destruction of adnexa
Vascular proliferation ++ Vascular proliferation ---
Stromal fibrosis ++++ Stromal fibrosis ---

60. MODERN CLASSIFICATION OF CUTANEOUS
PSEUDOLYMPHOMA
1. Rijlaarsdam and Willemze’s classification
2. Burg and Braun-Falco classification

61. RIJLAARSDAM AND WILLEMZE’S CLASSIFICATION
1. Cutaneous T-cell pseudolymphoma
a) Primarily with stripe-like infiltration
- Lymphomatoid drug eruptions
- Lymphomatoid contact dermatitis
- Actinic reticuloid
- Nodular scabies
- Idiopathic forms
- Clonal

62. b) Primarily with nodular infiltration
- Drug induced
- Persistent nodules after insect bites
- Nodular scabies
2. Cutaneous B-cell pseudolymphoma
- Cutaneous lymphocytoma from Borrelia burgdorferi
- Cutaneous lymphocytoma after antigen injection
- Cutaneous lymphocytoma resulting from tatoo
- Cutaneous lymphocytoma after Herpes Zoster
- Idiopathic
- Clonal

63. BURG&BRAUN-FALCO; KERL&SMOLE CLASSIFICATION
A) Infiltration from non-lymphoid cell
- Neuroblastoma ,Merkel cell carcinoma
B) Neoplasm rich in lymphocytes
- Cutaneous lymphadenoma (variant of
trichoblastoma)
C) Stroma reaction in epithelial displasia and
malignant neoplasms of the soft tissues

64. D) Diseases which are not directly related to the skin
- Rosai-Dorfmann’s disease, Castleman’s disease,
Kikuchi’s disease
E) Classical dermatological diseases resembling
cutaneous lymphoma
- atypical lymphocyte lobular , panniculitis, lymphomatoid
dermatitis, lymphomatoid folliculitis.
F) Specific cutaneous pseudolymphoma units
- angiolymphoid hyperplasia with eosiniphilia ,Kimura’s
disease, APACHE

65. RECENT ADVANCES
 Genotypic analysis has made a major contribution in the
last decade.
 Now many pseudolymphomas are considered cutaneous
lymphomas:
a) regressing atypical histiocytosis
b) granulomatous slack skin disease
c) pagetoid reticulosis
Cutaneous
T-cell
lymphoma

66. CLINICAL COURSE AND MANAGEMENT
1. Anti-convulsant induced pseudolymphoma
- Usually regress after 3-4 weeks of withdrawal
- lymphoma has been reported following a period of many
years of drug therapy.
- Phenytoin
2. Other lymphomatoid drug eruption
- complete resolution within 1 to 8 weeks after
discontinuation of the causative drug.

67. 3. Lymphomatoid contact dermatitis
- Topical corticosteroids
- Avoidance of the responsible allergens
4. Nodular scabies
- Antiscabetic therapy is often ineffective
- Spontaneous resolution occurs frequently
- Intralesional corticosteroids are beneficial

68. 5. Actinic reticuloid
- A several-month course of azathioprine leads to a
remission in about two thirds of patients
- Cases of actinic reticuloid progressing to lymphoma have
been reported
- Various combinations of photochemotherapy, UVB
phototherapy, systemic corticosteroids, azathioprine, and
cyclosporine may be beneficial

69. 6. Lymphomatoid papulosis
- disappear without treatment in 3 to 6 weeks
- lymphomas develop in 10% to 20% of patients
- Malignant evolution cannot be predicted by clinical or
histologic features, T-cell receptor gene rearrangement, or
DNA flow cytometry
- Continued observation is essential
Mycosis fungoides 38%
Hodgkin’s lymphoma 24%
CD30+ anaplastic large cell lymphoma 32%

70. 5. Borrelial lymphocytoma
- penicillin 1 gm orally three times daily or
- doxycycline 100 mg orally twice daily for 2 weeks.
- Although, B. burgdorferi-associated Cutaneous B-cell
Lymphoma has been reported.

71. REFERENCES
1. Ploysangum T, Breneman DL, Mutasim DF. Cutaneous
pseudolymphomas. J Am Acad Dermatol. June
1998;38(6):877-98.
2. Bergman R. Pseudolymphoma and cutaneous
lymphoma:Facts and controversies. Clinics of
Dermatology. 2010;28:568-74.
3. Cerroni L. Lymphoproliferative lesions of skin. J Clin
Pathol 2006;59:813–26.

72. 4. Kiyohara T et.al. Linear acral pseudolymphomatous
angiokeratoma of children (APACHE): Further evidence
that APACHE is a cutaneous pseudolymphoma. J am
acad dermatol. Feb 2003;48:15-7.
5. Shtilionova S, Drumeva P, Balabanova M, Krasnaliev.
JofIMAB. 2010;16(3):100-1.
6. Kutlubay Z, Pehlivan O, Engin B. Cutaneous
peudolymphomas. J Turk Acad Dermatol. 2012;6:1-7.
7 Rosai J. Rosai and Ackerman’s Surgical Pathology. 10th
Edition. New York: Mosby; 2011.

73. 8. Elder DE. Lever’s Histopathology of Skin. 11th Edition:
Lippincott Williams and Wilkins;2014.
9. Sternberg SS, Mills SE, Carter D. Sternberg’s diagnostic
surgical pathology. 5th Edition. Philadelphia:Wolters
Kluwer Health/Lippincott Williams & Wilkins;2010.
10. Slater D. Cutaneous pseudolymphoma. Underwood J,
Pignatelli M. Recent Advances in Histopathology 22.
London:Royal Society of Medicine Press Ltd;2007.