1. Cutaneous Lymphoid Hyperplasia, Cutaneous T-Cell Lymphoma, & Cutaneous B-Cell Lymphomas
JoAnne M. LaRow, DO
May 4, 2004

2. Cutaneous Lymphoid Hyperplasia
Collection of lymphocytes with other inflammatory cells in the skin
Aka: lyphocytoma cutis, lymphadenosis benigna cutis (LABC), Spiegler-Fendt sarcoid
Not a single dx state
Rxn to a range of stimuli
Possibilities:
medications,
infections
arthropod bites
UV light
Borrelia burgdorferi infection

3. Clinical features Seen most often in adults; more often in women
A firm, erythematous-violaceous papule on head, neck, or upper extremity
Localized clusters of papules are often seen
Mostly there is no surface change-but some slight scale & follicular accentuation has been described

4. Erythematous nodules characteristic of this dx

5. Coalescing erythematous follicular papules and raspberry-like nodules on the right shoulder.

6. Cutaneous lymphoid hyperplasia
Low: in cutaneous lymphoid hyperplasia there are nodular aggregates of mononuclear cells within dermis that may extend into subcutaneous fat;infiltrate may be diffuse or as seen here nodular in architecture

7. Cutaneous lymphoid hyperplasia: demonstrates germinal center formation, presence of tingible-body macrophages, & a mantle zone

8. Cutaneous lymphoid hyperplasia
High:germinal center consists of central large mononuclear cells with vesicular nuclei-these are surrounded by a mantle of small lymphocytes

9. Pathology
Superficial & deep nodular or diffuse infiltrate of lymphocytes admixed with histiocytes & occasional plasma cells & eos
Dense dermal infiltrate-recapitulating nodal architecture
In florid cases, germinal centers with prominent tingible-body macrophages are seen
A mantle zone may surround the lymphoid follicles
Diagnosis can usually be made on routine H&E, with addition of immunostains if H & E non-diagnostic

10. Cutaneous Lymphoid Hyperplasia
May progress to lymphoma
Immunosuppression may aggravate the infiltrate and may regress with immunosuppression is removed
Differential dx: lymphoma cutis, lymphocytic infiltrate of Jessner, & occasionally adnexal tumors
Can be differentiated from lymphoma by presence of reactive germinal centers, a polymorphous infiltrate of lymphocytes & histiocytes & presence of eos &/or plasma cells
Most CLH demonstrates brisk B lymphocytic infiltrate; Jessner’s generally T-cell predominant

11. Immunophenotyping
Predominance of T cells, B cells localized to germinal centers
Cells with both kappa & lambda expression are present
Predominance of CD4+ T helper lymphocytes, with a significant minority population of CD8+ cytotoxic/suppressor T cells
Positive CD68 demonstrates presence of abundant histiocytes

12. Cutaneous lymphoid hyperplasia
The lack of acanthosis, "bottom-heavy" infiltrates, light-chain expression of monotypical B-cells, and immunoglobulin gene rearrangements (75%) provide strong evidence for the diagnosis of B-cell lymphoma
A careful monitoring of these patients for the development of lymphoma is necessary

14. Cutaneous T Cell Lymphomas

15. Primary Cutaneous T-Cell Lymphomas
Dx:
Obtain 4-5 mm punch bx/or excisional or incisional bx from most representative skin lesion
Lymphoma vs benign condition?
Atypical T-cell infiltrates are found also in lymphoid drug rxns(pseudolymphoma)
Immunohistochemical stains aid in dx(use antibodies reactive with cell-surface or cytoplasmic molecules

16. Mycosis Fungoides Most common type of CTCL
Accounts for 50% of all primary cutaneous lymphomas
Term reserved for classical ‘Alibert-Bazin’type-characterized by typical evolution of patches, plaques,tumors or for clinicopathologic variants showing a simiilar cclinical course
Malignancy of T-lymphocytes, almost always MEMORY T-CELL
Race: MF is more common in black than in white patients (incidence ratio 1.6).
Sex: MF occurs more frequently in men than in women (male-to-female ratio of 2:1).
Age: The most common age at presentation is 50 years; however, MF also can be diagnosed in children and adolescents with apparently similar outcomes.

17. Mycosis Fungoides Patch Stage – pre-mycotic, severe pruritis.
Plaque Stage – infiltrated plaque
Tumor Stage – when de novo, called d’ emblee form
Erythroderma – Rare

18. MF Staging
TNMB system on skin (T) node (N), viscera (M), and blood (B)
T1 – Skin involvement <10%
T2 – Skin involvement >10%
T3 – Tumor
T4 – Erythroderma

19. MF Staging N0 – normal nodes N1 – palpable but not pathologically MF
N2 – not palpable but pathologically MF
N3 – clinically and pathologically involved
M0 B0 - Viscera and blood not involved
M1 B1 - Viscera and blood involved

20. MF Staging Stage IA – T1, N0, M0 – 8-9% progress
Stage IB – T2, N0, M0 – years surv
Stage IIA – T1-2, N1, M0 – 7.7 years
Stage IIB – T3, N0-1, M0 – 3-8 years surv
Stage IIIA – T4, N0, M0 – years
Stage IIIB – T4, N1, M0 – years
Stage IVA – T1-4, N2-3, M0
Stage IVB – T1-4, N0-3, M1

22. Limited patch/plaque stage dx (1a)
Patches on buttocks involving <10% of skin surface
Atypical lymphocytes in typical linear configuration along epidermal basal layer

23. Generalized patch/plaque stage
Extensive patches & plaques involving >10% of skin surface; pronounced epidermotropism with formation of small nests of atypical cells (Pautrier’s microabscesses)

24. Tumor stage
Multiple skin tumors in combination with typical patches & plaques; diffuse dermal infiltrates of medium-sized to large neoplastic T cells

25. Cutaneous T-cell lymphoma
Medium: epidermotropic T cells (“Pautrier microabscesses”) which is a feature that helps differentiate this lesion from cutaneous B-cell lymphoma

26. Lymph nodes in MF
Extracutaneous involvement is more clinically evident as the stage and extent of MF increases
Peripheral lymphadenopathy is the most frequent site of extracutaneous involvement in MF
Evaluate palpable lymphadenopathy by obtaining a biopsy because the result influences the patient’s stage, prognosis, and treatment.

27. MF Workup CBC – to review the buffy coat smear for Lymph nodes CMP
Liver Function to include LDH (aggressive) and transaminase (liver involvement) values
CXR
If lymph nodes are palpable
CT to access abdominal and pelvic nodes
Lymph node biopsy

29. Histologic Findings The criteria for diagnosis include the following:
A bandlike upper dermal infiltrate of lymphocytes and other inflammatory cells, with no grenz zone, is present.
Epidermotropism of mononuclear cells occurs.
When a clear halo surrounds an intraepidermal mononuclear cell singly or in clumps, this is called a Pautrier microabscess. Its presence is suggestive of MF, but it is not necessary for diagnosis.
Little spongiosis of the epidermis is found.
Lymphocytes have nuclei that are hyperchromatic and convoluted or cerebriform.

33. tx Pts with limited patch/plaque stage dx: topical corticosteroids
Topical mechlorethamine (nitrogen mustard) & carmustine (BCNU) effective in early stage
Nitrogen mustard, either dissolved in complete water or used as an ointment-based preparation results in complete remission in approx % of pts with stage IA-B
Tx with BCNU has similar remission rate
Total skin electron beam irradiation (TSEB) with energy of 4-6 MeV is highly effective in pts with skin-limited MF
Total dose is 36 Gy administered in fractions over8-10 weeks

34. TSEB is most effective in pts with stage IA-B with complete response rates of over 80%
Most centers incorporate TSEB with PUVA or topical chemo
Local radiotherapy with X-ray or preferably electron beam for single tumors in pts with plaque stage
Several types of phototherapy can be used: UVA irradiation following photosensitization with 8-methoxypsoralen (PUVA), broad-band & narrow-band UVB & UVA-1 therapy(new therapies-unsure of how they compare with first 2)
ECP may be effective in pts with SS
Systemic chem: used in pts with unequivocal lymph node or visceral involvement or progressive skin tumors
CHOP;80-90% response-but response short

35. Biologic response modifiers: aimed at potentiating the host’s immune response to neoplastic cells
These are: cytokines, retinoids, immunotoxins & vaccination therapy
BRM are most effective when combined with (or preceded by) traditional therapies
Interferon alpha (most common BRM) response rate 50% with 17% experiencing complete remissions
Retinoids like isotretinoin, etretinate & acitretin A a novel RXR-selective retinoid (bexarotene) used as single agents are roughly comparable to IFN-alpha
Combination of retinoids + PUVA (RePUVA) shows a response similar to PUVA alone-but less tx & lower UVA dose cumulatively

36. New immunomodulatory therapies in MF are: receptor targeted cytotoxic fusion proteins (DAB389IL2; denileukin difitox), cytokines (IL-12) & various vaccination stragegies
DAB389IL12 is a fusion protein, in which diphtheria toxin is linked to IL-2
It binds to the high affinity IL-2 receptor expressed by neoplastic T cells in MF
Result is inhibition of protein synthesis & apoptosis
Overall & complete response rates are 30% & 10% respectively
Vaccination with peptides or peptide-loaded dendritic cell is currently under investigation

44. Variants of MF
Apart from classical Alibert-Bazin type of MF, many clinical variants reported
Bullous & hyper-or hypopigmented MF have clinical behavior like MF
In contrast follicular MF, pagetoid reticulosis & granulomatous slack skin have distinctive clinicopathologic features

46. Follicular MF AKA:Mf-associated follicular mucinosis
Folliculocentric or pilotropic MF
Variant found in 10% of MF pts;mostly in adults;men>women
Pt presents with (grouped) follicular papules, acneiform lesions, indurated plaques & sometimes tumors
Mostly on head & neck area
Skin lesions may be associated with alopecia
Infiltrated papules in eyebrow region are common
Pruritus more common then MF;secondary bacterial infections may be present

47. Pagetoid Reticulosis AKA:Localized epidermotropic reticulosis
Woringer-Kolopp disease
Acral mycoses fungoides
Unilesional MF
Mycosis fungoides palmaris et plantaris

48. Pagetoid Reticulosis 0.6% of all MF cases
Woringer-Kolopp variant: localized type
Ketron-Goodman variant: disseminated
Long duration without progression to frank lymphoma is the clinical hallmark of Woringer-Kolopp
Ketron-Goodman type is a manifestation of aggressive CD-8+epidermotropic CTCL or of classical tumor stage MF
TOC: local excision or radiation therapy maybe curative.

49. Clinical features
Solitary psoriasiform or hyperkeratotic patch or plaque
Usually localized to an extremity
Slowly progressive
Extra-cutaneous dissemination or disease-related deaths have not been reported (in contrast to MF)

50. Pathology
Hyperplastic epidermis with marked infiltration by large atypical pagetoid cells, singly or arranged in nests or clusters
Atypical cells have medium-sized or large, sometimes hyperchromic & cerebriform nuclei and abundant, vacuolated cytoplasm
Superficial dermis may have an infiltrate of mostly small lymphocytes, but rarely contains neoplastic T cells

51. Pagetoid reticulosis: solitary plaque
Purely intraepidermal proliferation

52. Scattered plaque-like lesions on both lower extremities
Scattered plaque-like lesions on both lower extremities. Ketron-Goodman disease

53. Band-like infiltration of lymphoid cells in lower epidermis and upper dermis. Intra-epidermal infiltrate were medium- to large-sized atypical cells. Lymphoid cells infiltrating upper dermis revealed no overt atypia

54. Granulomatous Slack Skin
Extraordinarily rare type of CTCL
Characterized by slow development of folds of lax skin & a granulomatous infiltrate
Affects adolescents & adults
Characterized by pendulous lax skin
Predilection for axillae & groin
1/3 of reported pts had an association with Hodgkin’s dx
An association with classical MF has also been described

55. Pendulous fold of atrophic lax skin in the right inguinal area

57. Pathology & tx
Dense granulomatous dermal infiltrates containing atypical T cells with cerebriform nuclei, macrophages & often many multinucleated giant cells
Destruction of elastic tissue & elastophagocytosis by multinucleated cells
Epidermis is infiltrated by small atypical T cells with cerebriform nuclei, as in classical MF
Atypical T cells have a CD3+, CD4+, CD8+ phenotype
Radiotherapy may be effective; rapid recurrences after surgical excision have been reported

58. Sezary Syndrome Leukemic phase of mycosis fungoides
Generalized erythroderma, superficial lymphadenopathy, atypical cells in circulating blood
Erythroderma from onset with leonine facies, eyelid edema, ectropion, alopecia, palm and sole hyperkeratosis
Pruritis, burning, chill and profuse sweating

59. definition
Historically traid defines it: erythroderma, generalized lymphadenopathy, & neoplastic T cells (Sezary cells) in skin, lymph nodes & peripheral blood
No consensus on diagnositc criteria

60. Electron photomicrograph of a skin a skin bx showing characteristic Sezary cells

61. Clinical features
Erythroderma, which may be associated with marked exfoliation, edema, & lichenification
It is intensely pruritic
Lymphadenopathy, alopecia, onychodystrophy, & palmoplantar hyperkeratosis are common
Overt clinical picture may be preceeded by by non-diagnostic dermatits
Bone marrow may contain neoplastic cells, but real replacement of bone marrow tissue is rare
Poor prognosis: 10-20% survival
Most pts die of opportunistic infections due to immunosuppression

66. tx Being a systemic dx(leukemia) by definition systemic tx is required
Prolonged tx with combination of low-dose chlorambucil & prednisone, or with methotrexate is often effective in controlling dx
CHOP or CHOP-like regimens may produce higher response rates, these responses are short-lived
ECP, either alone or in combination with other tx modalities has been suggested as toc in SS & erythrodermic MF-response rate of 30-80%; complete response in 14-25%
There are no controlled randomized trials showing ECP superiority over traditional low-dose chemo

67. Primary Cutaneous CD30-Positive Lymphoproliferative Disorders
Second most common group of CTCL
Accounts for approx. 30% of CTCL
Includes primary cutaneous CD30-positive large T-cell lymphoma, lymphomatoid papulosis (LyP), & borderline cases

70. Lymphomatoid Papulosis
LyP has a chronic indolent course in most patients;
estimates indicate that as many as 10-20% of LyP patients have a history of associated malignant lymphoma (ALCL, HD, or mycosis fungoides [MF]) prior to, concurrent with, or subsequent to the diagnosis of LyP.
Race: Black persons may be less affected than other racial groups.
Sex: No consistent sex predominance is found in studies.
Age: LyP may develop at any age, usually in the third to fourth decade

71. Lymphomatoid Papulosis
Chronic, recurrent, self-healing papulonecrotic or papulonodular skin dx with histo features suggestive of a CD30+ malignant lymphoma
Introduced by Macuaulay in 1968-still unclear whether maligant. Premalignant, or benign
Should probably be regarded as a low-grade malignant CTCL
Etiology unknown; ?viral
Accounts for 185 approx of all CTCL
Youngest pt affected was 18 months-oldest 84; average age yrs; male to female ratio: 1.5:1

72. LP
Typical lesions are red-brown papules & nodules that may develop central hemorrhage, necrosis, & crusting & spontaneously disappear within 3-8 weeks
Characteristically, skin lesions in different stages of evolution coexist
Papulonodules may leave transient hypopigmented or hyperpigmented macules & superficial atrophic(varioliform) scars or disappear completely
Predominant sites are trunk & limbs
In up to 20% of pts LyP may be preceded by, asssociated with , or followed by another type of malignant lymphoma-generally MF or a CD30+ large cell or Hodgkin’s dx
Usually prognosis is excellent

73. LyP-pathology
Variable , extremely; 3 histologic types of LyP described:A,B, & C
Type A: Characterized by large (25-40 mm) CD30+ atypical cells with polymorphic convoluted nuclei and a minimum of 1 prominent nucleolus. These large cells resemble Reed-Sternberg cells when binucleate. Type A LyP is the most common histologic variant.
Type B: Characterized by smaller (8-15 mm) atypical cells with hyperchromatic cerebriform nuclei resembling the atypical lymphocytes in MF. CD30+ large cells are rare, but epidermotropism is more common in this variant.
Type C: Characterized by monotonous population or large clusters of large CD30+large cell lymphomas

74. LyP-Tx Unsatisfactory
Topical or systemic corticosteroids or antibiotics are ineffective
Aggressive txs like systemic chemo or total electron beam irradiation may produce complete remissions but lesions reappear
In pts with few lesions non-scarring-no tx
In cosmetically disturbing lesions:low-dose oral methotrexate is most effective therapy for reducing lesion numbers

75. Lymphomatoid Papulosis
Type C (diffuse large cell type): Characterized by sheets of CD30+ anaplastic large cells

76. Clinical presentation with papulo-necrotic skin lesions at different stages of evolution
Detail of dermal infiltrate showing mixed inflammatory infiltrate with scattered (CD30-pos) large anaplastic cells (LyP, type A)

77. Lymphomatoid papulosis: high power-infiltrate is heterogeneous & includes neutrophils & eos & small lymphocytes & few large anaplastic cells

78. Lymphomatoid papulosis:high
Lymphomatoid papulosis:high. CD30 immunostain-few large neoplastic CD30+cells-in contrast to anaplastic large cell lymphoma do not form large sheets or nodular clusters

79. Treatment of LyP
Mid-to-high potency topical steroids to hasten resolution.
Low-dose weekly methotrexate is a safe and effective treatment for suppressing LyP; however, the disease recurs within 1-2 weeks after ending medication.
Oral psoralen plus UV-A phototherapy (PUVA) also effectively treats and suppresses the disease.
carmustine, topical nitrogen mustard, intralesional interferon, low-dose cyclophosphamide, chlorambucil, and dapsone help disease suppression.

81. Primary CTCL other than Mycosis Fungoides
CD30-positive cutaneous T-Cell Lymphoma
Secondary Cutaneous CD30 positive large-cell lymphoma
Non-MF CD30-negative cutaneous large T-cell lymphoma
Non-MF CD30-negative cutaneous pleomorphic small or medium sized cell lymphoma
Subcutaneous (Panniculitis-Like) T-Cell Lymphoma
Nasal/Nasal Type T/NK Cell Lymphoma

82. CD30-positive cutaneous T-Cell Lymphoma
Consist of large tumor cells, most expressing the CD30 antigen
No history of LyP, MF, or CTCL’s
Present as solitary or localized skin lesions with tendency to ulcerate and have spontaneous regression
Rare in children, occur more frequently in males
5 year survival rate 90%
Highly responsive to radiotherapy
Lesions can be surgically excised

83. Primary Cutaneous CD30 + Large T-cell lymphoma
Histologically show diffuse non-epidermotropic infiltrates with cohesive sheets of large CD30 + tumor cells
Mostly having morphologically of anaplastic cells, with round, oval, or irregularly shaped nuclei, prominent (eosinophilic) nucleoli & abundant cytoplasm
The t(2;5) translocation is predominantly found in children with systemic CD30+ anaplastic lymphoma is not found
Tx:radiotherapy for few localized nodules or tumors
Debatable whether tx with doxorubicin & multi-agent chemo agents should be done; skin relapses after CHOP are common & spontaneous regression may occur

84. Primary Cutaneous CD30+Lymphoma
Best tx is radiation or low-dose methotrexate (few lesions)
Multi-agent chemo (those with extracutaneous dx)

85. Characteristic clinical presentation with a solitary ulcerating tumor; dermal infiltrate with cohesive clusters of large(CD30+) anaplastic cells with pronounced eosinophilic nucleoli & abundant cytoplasm

86. Non-MF CD 30 Negative Cutaneous Large T-Cell lymphoma
CD30-neg large neoplastic cells without prior or concurrent MF
Differentiation from small/medium sized pleomorphic CTCL is based on presence of >30% large pleomorphic T cells
May present with solitary or localized nodules or tumors; more commonly present with generalized lesions
Prognosis is poor: overall 15% 5- year survival
No difference in survival between cases of CD3+, CD4+,, CD8- & cases of CD3+, CD4+, CD8 +phenotype

87. Rapidly growing nodules & tumors
Rapidly growing nodules & tumors. No patches present, rather deep plaques present for 2 weeks

88. CD30-neg Cutaneous Large Cell Lymphoma
Pathology: nodular or diffuse infiltrates with variable numbers of medium-sized-large pleomorphic or immunoblasic-like T cells
Cells represent at least 30% of total tumor cell population
Must be differentiated from CD30+ LTCL, CD56+ blastic NK-cell lymphomas
Absence of prior or concurrent patches & plaques is a decisive criterion
Tx:multi-agent chemo;only pts with localized or solitary dx may radiotherapy considered as initial tx

89. Non-MF CD 30 Negative Cutaneous Small or Medium Size Cell T-Cell lymphoma
Differentiate from large-cell type by having less than 30% large pleomorphic cell.
Similar to large type clinically
Prognosis is better than large cell type. 50% 5 year survival.
Radiation tx or surgical excision for solitary localized skin lesions; interferon alfa, or cyclophosphamide are effective in more generalized dx

90. Large cell anaplastic lymphoma
Cells are large with hyperchromic nuclei;bizzare forms & mitotic figures seen

91. Large cell anaplastic lymphoma
Medium power: dense sheets of atypical cells admixed with inflammatory cells, freq. Eos
A number of atypical cells show more than 1 nucleus

92. Cutaneous anaplastic large cell lymphoma
Low power: dense infiltrate occupying entire dermis
Associated ulceration of epidermis

93. Subcutaneous (Panniculitis-Like) T-Cell Lymphoma
Clinically presents with subcutaneous nodules
Usually on lower extremities
Frequently diagnosed as having erythema nodosum or other forms of panniculitis
Systemic symptoms like fever, fatigue, & wt. Loss may occur
May be complicated by hemophagocytic syndrome-rapidly progressive
Cases with TCRgamma/epsilon+phenotype have worse prognosis than TCRalpha/beta+

94. A, Marked edema of right calf at time of presentation
A, Marked edema of right calf at time of presentation. B, Erythematous nodules with associated vascular ectasia on abdominal wall.

95. Subcutaneous Panniculitis-Like T-Cell Lymphoma
Pathology: subcutaneous infiltrate simulate pannicultis-with mixture of neoplastic pleomorphic T cells of various sizes & often many macrophages
Overlying epidermis & dermis are typically uninvolved
Rimming of individual fat cells by neoplastic T cells is a diagnostic feature
Tx:early stage: systemic corticosteroids
However pts with a hemophagocytic syndrome prognosis is poor despite aggressive multiagent chemo

96. Subcutaneous Panniculitis-Like T-Cell Lymphoma
Subcutaneous infiltrate with characteristic rimming of individual fat cells by the neoplastic T cells

97. High-power view of infiltrate showing random atypical lymphocytes

98. Cutaneous B-Cell Lymphoma- types:
Primary Cutaneous Follicular Center Cell Lymphoma
Primary Cutaneous Immunocytoma/Marginal Zone Lymphoma
Intravascluar Large B-Cell Lymphoma
Primary Cutaneous Plasmacytoma

99. B-cell lymphomas of the skin
Aka Cutaneous B-cell lymphoma & SALT-related B-cell lymphoma
Group of malignant lymphomas whose primary site is the skin
Derived from B lymphocytes in different stages of differentiation
Skin can be the site of secondary involvement by extracutaneous (usually nodal) B-cell lymphomas
Most are low-grade malignancies, indolent behavior & good prognosis

100. Immunohistochemical & molecular genetic techniques show that previously classified cases of B-cell pseudolymphomas represent low-grade malignant B-cell lymphomas of the skin
Precise classification can be achieved after complete synthesis of clinical, histopathologic, immunophenotypic, & molecular features done
Terminology is not uniform & varies depending on medical center
Most cases tx consists of local radiotherapy; in case of 1-2 lesions sx excision is an option; systemic chemotherapy is needed in a small proportion of pts

101. Classification
EORTC classification divides into 3 major types & 2 provisional categories
Follicle center cell lymphoma
Immunocytoma/marginal zone lymphoma
Large B-cell lymphoma of the leg
Provisional categories:
Plasmacytoma
Intravascular large cell B-cell lymphoma

103. Nomenclature
In EORTC classification primary cutaneous lymphoma was defined as ‘presence of dx limited to the skin for at least 6 months after complete staging
Bolognia believes definition should read:malignant lymphomas confined to skin at presentation, based on 2 arguments:
A. aggressive lymphomas arising within skin may disseminate prior to 6 months
B. pts need to be tx at time of presentation & therefore dx is needed then not 6 months later

104. Primary Cutaneous Follicular Center Cell Lymphoma
AKA B-Cell lymphoma of follicular center cell origin
AKA Reticulohistiocytoma of the dorsum/Crosti’s lymphoma
Neoplastic proliferation of germinal center cells confined to skin
Common subtype
Multiple papules, plaques nodules in one anatomic region surrounded by patches of erythema
Ulceration is common
Usually asymptomatic-LDH is normal
2/3 of case on the trunk, 1/5 on the head and neck
15% on the leg

105. Primary Cutaneous Follicular Center Cell Lymphoma
M:F = 2:1
Prognosis: Head and neck 100% 5 yr surv.; Leg lesion of people over 70, 50% 5 yr surv.
Recurrences seen in up to 50%, dissemination to lymph nodes or internal organs is rare
Stains with B-Cell marker CD 20, monotypic for immunoglobulin production of kappa or lambda chain, not both

106. Cutaneous follicle center cell lymphoma: large ulcerated tumors on the scalp surrounded by infiltrated erythematous nodules & plaques

107. Cutaneous follicle center cell lymphoma:large ulcerated tumor on the back
Note surrounding erythematous papules, patches & plaques

108. Cutaneous lymphoma
57-yr-old woman with B-cell lymphoma developed asymptomatic erythematous-lavender plaques & tumors on face & scalp

112. Cutaneous follicular B-cell lymphoma
Low: multinodular pattern seen-lymphomatous infiltrate situated at dermal-subcutaneous junction-composed of small cleaved follicular center cells arranged as coalescing follicles

113. Cutaneous follicular B-cell lymphoma
Medium: absence of tingible-body macrophages

114. Cutaneous B-cell lymphoma
Studies should be performed are: CBC, CMP, BMBx, CT of chest, abdomen, & pelvis
Flow cytometry of peripheral blood & bone marrow are optional-can be helpful in low-grade lymphomas
Gallium scans are being replaced by PET scans

115. Cutaneous diffuse B-cell lymphoma
High:cytologically atypical lymphoid cells admixed with nuclear fragments

116. Cutaneous diffuse B-cell lymphoma
High: not all cells are large & atypical
In this example cells are small, hyperchromic, & monotonous in appearance

117. Cutaneous diffuse B-cell lymphoma(low): dense dermal infiltrate of basophilic cells not involving overlying epidermis
Typically, B-cell lymphoma has a bottom heavy infiltrate-a significant portion of infiltrate involves lower dermis
Medium: dermal infiltrate may be nodular & cells permeate between bundles of reticular dermis

118. Cuatneous immunocytoma: domeshaped erythematous nodule with smooth surface
Surrounding area shows features of acrodermatitis chronica atrophicans

119. Primary Cutaneous Immunocytoma
Proliferation of small lymphocytes, lymphoplasmacytoid cells & plasma cells with monotypic intracytoplasmic immunoglobulins
Primary cutaneous immunocytoma differs from nodal cutaneous immunocytoma b/c pts do not show features of Waldenstrom’s macroglobulinemia & have an excellent response to tx
Some consider cutaneous immunocytoma & cutaneous MZL to be a single entity

120. Pts present with solitary or grouped erythematous-red-brown plaques or dome-shaped tumors
Favors lower extremity
Generalized lesions are rare & called miliary type of cutaneous immunocytoma
Sometimes resolution of lesions causes secondary anetoderma due to loss of elastic fibers
Can arise from areas of acrodermatitis chronica atrophicans & may be linked to Borrelia spp.
More frequently linked to B-cell lymphoma
Skin lesions asymptomatic;& no B- symptoms;normal LDH
Excellent prognosis; although local recurrence may occur

121. Clinical features
Present with solitary or grouped erythematous to red-brown plaques or dome-shaped tumors favoring lower extremities
Generalized lesions are rare
Sometimes resolution results in secondary anetoderma-due to loss of elastic fibers in area of tumor infiltrate
May arise in areas affected by acrodermatitis chronica atrophicans-may be linked to infection by Borrelia spp.
Serum LDH levels are usually normal
Prognosis is excellent recurrences

122. Cutaneous Marginal Zone Lymphoma
Variant of low-grade malignant primary cutaneous B-cell lymphoma
Closely related to immunocytoma & MALT-lymphomas
Terminology is inconsistent in different centers
Lesions designated in past as cutaneous atypical lymphoid hyperplasia with monotypic plasma cells probably represent examples of cutaneous marginal zone lymphoma

123. Cutaneous Marginal Zone Lymphoma
Pts present with recurrent red-brown papules, plaques, & nodules
Localized preferentially to upper extremities or trunk
Generalized lesions may be seen rarely
Ulceration rarely, if ever occurs; usually asymptomatic, & no B symptoms, normal LDH
Prognosis : excellent

124. Solitary erythematous nodule on upper arm

125. Multiple, erythematous papules on the arm

127. Intravascular Large Cell B-Cell Lymphoma of the Skin
Malignant proliferation of large B-lymphocytes within blood vessels
Formerly known as malignant angioendotheliomatosis
Renamed peculiar variant of non-Hodgkin’s lymphoma
Rare to have only skin involvement;usually systemic dissemination including CNS at onset
Pts present with indurated, erythematous or violaceous patches & plaques
Preferentially located on back & trunk & thighs
Clinical appearance not typical of lymphoma-more like purpura or panniculitis

128. Large erythematous tumor on scalp of an 11-month-old child

129. B-Lymphoblastic Lymphoma
Malignant proliferations of precursor B lymphocytes
Rare to have skin as primary site
All pts should be classified with, tx for systemic dx-even in absence of systemic dx at dx
In contrast to other B-cell lymphomas shows predilection for children & young adults
Pts present with solitary large erythematous tumors
Commonly on head & neck
Pts with primary dx have asymptomatic skin lesions of a few weeks duration
Those with secondary skin lesions are ill: B-symptoms

131. Large B-Cell Lymphoma of the Leg
LBCLL has large cell morphology & intermediate prognosis
Occurs almost exclusively in elderly pts, predominantly women
Pt presents with solitary or clustered erythematous or red-brown nodules
Located on distal aspect of one leg, lesions may arise on both legs too
Ulceration is common
Tumors with similar morphology & phenotypia can arise in areas other than legs

132. Large B-Cell Lymphoma of the Leg
Prognosis is less favorable than other cutaneous B-cell lymphomas
5-yr survival is 50% approx.
3 prognostic variables were independent predictors of behavior:
1.) morphology of infiltrate-predominantly large cells worse than predominantly large cleaved cells
2.) # of lesions at presentation-pts with more have worse prognosis
3.) location on legs-pts presenting with lesions on the legs have worse prognosis

133. Cutaneous Plasmacytoma
Characterized by a clonal proliferation of plasma cells primarily affecting the skin
No bone marrow involvement
Exceedingly rare
Its existence called into question ? Some cases may be MZL arising in different organs
Occurs most commonly in elderly men
Pt presents with solitary, clusteredor rarely, generalized erythematous, red-brown or violaceous cutaneous/subcutaneous plaques or tumors
Predilection for head & neck
Amyloid deposition is rare & serum & urine monoclonal protein neg

134. Cutaneous Plasmacytoma
Prognosis is controversial
Prognosis is probably related to tumor burden & pts with small solitary lesions have very good prognosis
Development of multiple myeloma & systemic soft-tissue mets have been seen in some
As with other pts with non-cutaneous plasmacytomas they should undergo an evalution for systemic dx : bone marrow bx/aspirate, protein electrophoresis, & serum & urine immunofixation

137. Cutaneous marginal zone B-cell lymphoma:
Top: small nodules of reactive lymphocytes(dark areas) surrounded by neoplastic marginal zone cells, lymphoplasmactoid cells, & plasma cells(clear areas)
Bottom: monotypic expression

143. tx Selected after exact classification found
After analysis of staging investigations
Overall condition of pt
Pts with secondary cutaneous lesions of extra-cutaneous B-cell lymphoma should be tx by oncology –not dermatology
Many pts with low-grade malignant primary lymphoma can be managed conservatively with watchful-waiting strategy
F/u for these pts should be q 6 months or at onset of new lesions/or symptoms

144. Most pts with low-grade B-cell lymphomas: FCCL,MZL, cutaneous immunocytoma- & who have solitary or few lesions can be tx with local radiotherapy, or sx excision followed by radiotherapy or surgical field
Wide margins-10-20cm beyond clinically apparent lesions have fewer recurrences
This is especially good for Crosti’s lymphoma
Surgical excision with narrow margins is valuable for pts with solitary well- circumscribed lesions
Recently few reports have appeared tx low-grade primary cutaneous B-cell lymphomas with antibiotics-achieving resolution in a percentage of pts
This type of tx is conceptually analogous to that of Helicobacter pylori-associated MALT lymphomas of the stomach-which if caught early can be cured with antib’s

145. Another tx for low-grade malignant primary cutaneous B-cell lymphoma is subcutaneous intralesional interferon-in particular interferon alfa-2a
Complete resolution in 50% of pts
Good for pts with multiple lesions at different body sites-radiotherapy difficult
Intralesional antiCD20 monclonal antibody (Rituximab) has been used to induce tumor reduction in pts with indolent primary CBL-response rate was better with IV
Next generation anti-CD20 monoclonal antibodies will be attached to 131 I or yttrium-being able to then tumor target & ‘radiotherapy’
Pts with disseminated lesions of diffuse FCCL or large B-cell lymphoma need systemic chemo-CHOP

146. Intravascular large B-cell lymphoma TOC is systemic chemo-regardless of staging
Pts with B-cell lymphoblastic lymphoma should be tx by hematology, aggressive chemo needed & BMT discussed
Cutaneous plasmocytomas can be tx with local radiotherapy
Systemic chemo reserved for pts with advanced dx
Neg staging is mandatory before tx of pts with cuatneous plasmocytomas