Diffuse Large B-Cell Lymphoma, Leg Type

 ~ 85% of all cases



• Subset of cases arise in skin of other sites (trunk, arms, head and neck)
image ~ 15% of cases

• Single or multiple lesions at time of presentation

• Relapse is common; 50% 5-year survival

• Treated with systemic chemotherapy plus rituximab




Microscopic




• Diffuse pattern of involvement in dermis

• Monotonous sheets of large, atypical-appearing immunoblasts or centroblasts

• Few small reactive T cells in background

• No centrocytes (or small B cells) present

• No epidermotropism


Ancillary Tests




• Pan-B-cell antigens (+), Bcl-2(+), Bcl-6(+)

• MUM1(+), FOXP1(+), IgM(+), CD10(-)

• FISH often shows rearrangements of MYC, BCL6, or IGH genes

• Monoclonal IGH gene rearrangements


Top Differential Diagnoses




• Primary cutaneous follicle center lymphoma (PCFCL)
image PCFCL cases with diffuse pattern and predominance of large centrocytes or centroblasts are challenging

image CD10(+), Bcl-6(+); Bcl-2 often (-); if positive, often weak and focal

• Systemic DLBCL involving skin

• EBV(+) DLBCL of elderly

• Plasmablastic lymphoma involving skin

• Monomorphic posttransplant lymphoproliferative disorder

image
Morphologic Features of PCDLBCL-LT
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) shows a diffuse infiltrate replacing the dermis with sparing of the epidermis image.


image
Morphologic Features of PCDLBCL-LT
The lymphoma cells in PCDLBCL-LT are large and strikingly round with centrally located nucleoli (immunoblasts).

image
CD20 IHC in PCDLBCL-LT
In this case of PCDLBCL-LT, the lymphoma cells are strongly CD20(+) and form cohesive-appearing sheets. The epidermis image is not involved, and a thin grenz zone is present image.

image
Bcl-2 Staining in PCDLBCL-LT
Most cases of PCDLBCL-LT are strongly and diffusely Bcl-2(+), as shown in this case.


TERMINOLOGY


Abbreviations




• Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)


Synonyms




• Primary cutaneous large B-cell lymphoma, leg type

• Primary cutaneous diffuse large B-cell lymphoma


Definitions




• Primary cutaneous diffuse large B-cell lymphoma composed exclusively of large transformed B cells
image Often occurs in lower leg(s) but can arise at other sites


ETIOLOGY/PATHOGENESIS


Cell of Origin




• Peripheral B cell of postgerminal center cell origin
image Immunophenotype: IRF-4/MUM1(+), FOXP1(+)

image High frequency of somatic mutations of IGH variable (V)-region genes


Possible Role of Antigen Selection




• Preferential use of certain IGH (IGHV) gene segments
image Suggests that antigen stimulation may be involved in pathogenesis


Role of Molecular Abnormalities




• Number of genetic rearrangements and deletions reported

• No abnormality consistently present


CLINICAL ISSUES


Epidemiology




• Incidence
image Rare

– 4% of all cutaneous lymphomas

– 20% of primary cutaneous B-cell lymphomas

• Age
image Elderly patients; median age: 7th decade

• Sex
image More common in women
– M:F ratio: 1:1.6; as high as 1:4 in some studies


Site




• Most cases arise in skin of lower leg(s): 1 or both legs may be involved
image ~ 85% of all cases

• Subset of cases arise in skin of other sites (trunk, arms, head and neck)
image ~ 15% of cases

image Similar morphologic and immunophenotypic characteristics

• Single or multiple lesions at time of presentation
image Some patients have dissemination at initial diagnosis


Presentation




• Red or blue-red cutaneous lesions
image Plaque, verrucous plaques, or deep plaques

image Nodular, tumoral lesions

image Often associated with ulceration

image Multiple lesions are common

• B symptoms in 10-20% of patients


Treatment




• Anthracycline-containing systemic chemotherapy plus rituximab

• Radiotherapy has role for localized lesions in elderly patients


Prognosis




• Relapse is common
• 40-50% 5-year survival rate

image Factors adversely correlated with prognosis

– Older age

– Multiple lesions at presentation

– Inactivation of CDKN2A

image Factors not correlated with prognosis

– Duration of lesions before diagnosis

– Gender, B symptoms, performance status, or serum lactate dehydrogenase level

– Bcl-2 or IRF-4/MUM1 expression


MICROSCOPIC


Histologic Features




• Diffuse pattern of involvement of dermis
image Infiltrate can be deep, often extending into superficial subcutaneous adipose tissue

• Cohesive, monotonous sheets of atypical-appearing large cells
image Centroblasts or immunoblasts

image Often very round nuclei; can also be oval

• Mitotic figures numerous

• Few small reactive T cells in background

• No centrocytes (or small B cells) present

• No epidermotropism


ANCILLARY TESTS


Immunohistochemistry




• Pan-B-cell antigens (+)
• Cytoplasmic IgM(+), IgD(+/-)

• Bcl-2(+), IRF-4/MUM1(+), FOXP1(+)

• Bcl-6(+), CD10(-)

• No follicular dendritic cell (FDC) meshworks

image CD21(-), CD23(-), CD35(-)

• T-cell antigens (-), LMP1(-), HHV8(-)

Apr 24, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Diffuse Large B-Cell Lymphoma, Leg Type
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