1. Cutaneous Lymphoid Hyperplasia, Cutaneous T-Cell Lymphoma, Other Malignant Lymphomas, and Allied Diseases
Rick Lin, DO, MPH March 18, 2003

2. Cutaneous Lymphoid Hyperplasia
Collection of lymphocytes with other inflammatory cells on the skin
Maybe monoclonal or mixed with both T or B cells
Caused by unknown stimuli
Medications,
infections,
insect bites

3. Cutaneous Lymphoid Hyperplasia
AKA Pseudolymphoma
May progress to lymphoma
Immunosuppression may aggravate the infiltrate and may regress with immunosuppression is removed

4. Cutaneous B-Cell Lymphoid Hyperplasias
Knowns as Speigler-Fendt sarcoid
Caused by Borrelia, infections, herpes zosters scars, tatoo, drugs
Appears as discrete firm of doughy cutaneous papules or nodules
Most lesions are asymptomatic, treatment not required
If caused by medication, medication should be removed

5. Cutaneous T-Cell Lymphoid Hyperplasias
Maybe idiopathic
Aka actinic reticuloid and chronic actinic dermatitis
Patient resembles mycosis fungoides
Histologically, dermal infiltrate that is band-like with no grenz zone.

6. Cutaneous lymphoid hyperplasia
Pseudolymphoma has to be distinguished from cutaneous lymphomas by the combination of clinicopathological correlation, histochemical studies, and, in selected cases, gene rearrangement studies
T cell lymhoma can be usually distinguished from T cell pseudolymphoma by the presence of prominent epidermotropism, large and atypical lymphocytes, and T cell gene rearrangements up to 90%

7. 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

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

9. Histological examination of the skin
The microscopic examinations revealed dense and diffuse infiltrates of cytologically benign-appearing lymphocytes and scattered histiocytes in the upper and mid dermis

10. Immunohistochemical examination of skin
Immunohistochemical examination of skin. Antibody against CD3+ (T-lymphocytes).

11. Cutaneous T Cell Lymphomas
Primary Cutaneous T-Cell Lymphomas
Not synonymous with MF
Up to 30% of primary CTCLs are not MF
Primary Cutaneous T-Cell Lymphomas other than Mycosis Fungoides

12. Primary Cutaneous T-Cell Lymphomas
Mycosis Fungoides
Pagetoid Reticulosis
Sezary Syndrome
Granulomatous Slack Skin
Lymphomatoid papulosis

13. Mycosis Fungoides
Malignancy of T-lymphocytes, almost always MEMORY T-CELL
Black>white
M:F = 2:1
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.

14. Mycosis Fungoides Patch Stage – premycotic, severe pruritis.
Plaque Stage – infiltrated plaque
Tumore stage – when de novo, called d’ emblee form
Erythroderma – Rare

15. 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

16. 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

17. 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

18. 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.

19. 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

25. 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.

29. Pagetoid Reticulosis Localized epidermotropic reticulosis
Woringer-Kolopp disease
Acral mycoses fungoides
Mycosis fungoides palmaris et plantaris

30. Pagetoid Reticulosis 0.6% of all MF cases
Woringer-Kolopp variant: solitary lesion
Ketron-Goodman variant: multiple lesions
Long durantion without progression to frank lymphoma is the clincal hallmark of Woringer-Kolopp
Local excision and radiation therapy maybe curative.

31. Scan power view. Hyperkeratosis is associated with papillomatosis

32. Medium power view. Keratinocyte enlargement is seen, and this can occur whenever there is an abnormal cell population in the lower epidermis. Clusters of  dark mononuclear cells are in all levels of the epidermis.

33. High power view. It would be difficult to distinguish between abnormal T cells and small, dark, lymphocytoid melanocytes in this field.

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

35. Band-like infiltration of lymphoid cells in lower epidermis and upper dermis. Intraepidermal infiltrate were medium- to large-sized atypical cells. Lymphoid cells infiltrating upper dermis revealed no overt atypicality.

36. 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

40. Prognosis Difficult to treat Median survival is 3 years
Low dose methotrexate has reasonable response rate of 50%
Photophoresis
Retinoid, interferon alfa, lowdose chlorabucil, prednisone, systemic chemo

41. Granulomatous Slack Skin
Rare variant of CTCL
Middle-age adult and gradually progress
Erythematous atrophic pendulous redundant plaque
Multinucleated giant cells replaces fat lobules histologically.

43. 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

44. Presentation
Primary lesion: Each erythematous papule evolves into a red-brown, often hemorrhagic, papulovesicular or papulopustular lesion over days to weeks.
Some lesions develop a necrotic eschar before healing spontaneously. Occasionally, noduloulcerative lesions may be present
Each papule heals within 2-8 weeks, leaving a hypopigmented or hyperpigmented depressed oval varioliform scar.
Large nodules and plaques may take months to resolve.
Distribution: Characteristically, lesions appear on the trunk and extremities, although the palms and/or soles, face, scalp, and anogenital area also may be involved.

45. Lymphomatoid Papulosis
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.

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

47. 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.

51. 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

52. CD30-positive cutaneous T-Cell Lymphoma
Present as solitary or localized skin lesions with tendency to ulcerate and have spontaneous regression
Rare in children, occur more frequesntly in males
5 year survival rate 90%
Highly responsive to ratiotherapy
Lesions can be surgically excised

53. Secondary CD30-positive cutaneous T-Cell Lymphoma
CD30 Positive CTCL arise from MF
Poor prognosis

54. Non-MF CD 30 Negative Cutaneous Large T-Cell lymphoma
Solitary or generalized plaque or tumor of short duration, no patch stage
Prognosis is poor, 15% 5 year survival
Malignant cells are pleomorphic large or medium cell types

55. 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 celll.
Similar to large type clinically
Prognosis is better than large cell type. 50% 5 year survival.
Radiation tx, interferon alfa, or cyclophosphamide are effective

56. 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
Poor prognosis

57. 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.

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

59. Cutaneous B-Cell Lymphoma
Primary Cutaneous Follicular Center Cell Lymphoma
Primary Cutaneous Immunocytoma
Intravascluar Large B-Cell Lymphoma
Plasmacytoma (Multiple Myeoloma)

60. Primary Cutaneous Follicular Center Cell Lymphoma
AKA B-Cell lymphoma of follicular center cell origin
AKA Reticulohistiocytoma of the dorsum
Multiple papules and nodules in one anatomic region.
2/3 of case on the trunk, 1/5 on the head and neck
15% on the leg

61. 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.
Stains with B-Cell marker CD 20, monotypic for immunoglobulin production of kappa or lambda chain, not both

65. Primary Cutaneous Immunocytoma
AKA Marginal Zone B-Cell Lymphoma
AKA MALT Type Lymphoma
SubQ nodule or tumor primaroily of the extremities or trunk
CD79, CD 20, and bcl-2 positive
5 years survival near 100%

68. Plasmacytoma Multiple Myeloma
Spectrum of solitary plasmacytoma to multiple plasmacytoma to multiple myeloma.
Neoplasm of B lymphcytes
Multiple myeloma is most common characterized by lytic bone lesions and infiltration of bone marry by plasma cells

69. Plasmacytoma Multiple Myeloma
Cutaneous plasmacytomas seen most commonly a secondary lesion in the setting of primary myeloma. Prognosis is poor.
When bone film and bone biopsy are normal but cutaneous lesions present, these are primary cutaneous plasmacytoma. Excellent prognosis.

70. Dense mononuclear infiltrate within entire dermis
Dense mononuclear infiltrate within entire dermis. This represent a primary cutaneous plasmacytoma

71. Neoplastic plasma cells, some with atypical features, are visible J Am Acad Dermatol 2000;43:962-5.)  

72. Plasmacytoma Multiple Myeloma
Numerous nonspecific skin lesions occurs in patient with multiple myeloma.
Amyloidosis
Cutaneous vasculitis
alopecia
Raynaud’s
Pyoderma gangrenosum

73. Hodgkin’s Disease
Vast majority of cutaneous Hodgkin’s disease report are type A lymphomatoid papulosis with Reed-Sternberg
Difficult to prove cutaneous disease

74. Malignant Histiocytosis
Rare, fatal occur in men in second to fourth decade of life
Solitary lesion or wide spread papule occur in 10% of cases
Onset of acute fever, hepatosplenomegly, and painful lymphadenopathy

75. Malignant histiocytosis
Malignant histiocytosis. Extensive superior orbital involvement in a young adult male.

76. Extensive erythrophgocytosis by histiocyte in marrow, liver, spleen

77. Leukemia Cutis 30% of Leukemia patient will have leukemia cutis
Vast majority of derm manifestation are from AML
Morphology: 60% multiple papules and nodules, 26% of infiltrated plaques
Subtypes and variants:
Granulocytic Sarcoma
Hairy-cell Leukemia
Nonspecific Condition associated with Leukemia

81. Cutaneous Myelofibrosis
Overproduction and premature death of atypical megakaryocytes in bone marrow
Inrease in platelet-derived growth factor
Extramedullary hematopoesis is the hallmark
Blast cells escape marrow and enter circulation and form tumor
Cutaneous EMH reported in 20 cases

82. Hypereosinophilic Syndrome
Icrease Eos with more than 1500 eos per cubit millimeter for 6 month or more.
Cardiac disease most frequent complication
90% patient are men between 20 to 50
Angioedema and urticaria lesions most common. Sometimes papules.

84. Angioimmunoblastic T-Cell Lymphoma
AKA Angioimmunoblastic T-Cell Lymphoma
Uncommon, affect middle age and elderly
Unspecific skin finding (pruritis, skin rash)
Unspecific histology finding (patchy perivascular dermal infiltrate)
Lymph node biopsy required for diagnosis

85. Polycythemia Vera Increase hermatocrite to 55% to 80%
Associated with aquagenic pruritis in 50% of the patients.
Elevation of blood and skin histamine
Tx – control of pruritis by antihistamin or PUVA. Referral to HemOnc