CLINICAL HISTORY:

Signs and symptoms:  A 73 year-old Caucasian woman presented with a 20 year history of violaceous masses of the left periocular area and left chest that have waxed and waned. These lesions were asymptomatic. 10 years ago, the lesions were biopsied and diagnosed as a low-grade B cell lymphoma without systemic involvement, and no chemotherapy was indicated at that time. Over the years, the lesions continued to wax and wane, but recently, the lesions have gotten larger.

Previous Treatment:  None.

Other information:  N/A

PHYSICAL EXAM:

There were large, violaceous nodules in the left peri-ocular area. There were also violaceous nodules, plaques, and patches on the left anterior chest and right posterior flank. No lesions were noted on the legs or lower body. There was no fever, lymphadenopathy, or hepatosplenomegaly.

Face

Left Breast

LABORATORY TESTS:

CBC and chemistries (including LFT's and Cr) were normal. A peripheral blood smear was normal. Bone marrow aspirate and biopsy were normal. Clonality studies revealed a lambda restriction. A PET scan showed uptake in the left periorbital subcutaneous tissue, left upper anterior chest wall, & right axilla. These areas corresponded to cutaneous lesions.

DERMATOHISTOPATHOLOGY:

The H & E biopsy shows expansion of the dermis by large atypical lymphoid cells with hyperchromatic nuclei, prominent nucleoli, and mitotic figures. These cells are growing in a diffuse pattern, and no follicular centers are seen. A grenz zone separates these lesional cells from the epidermis, which shows a lack of epidermotropism.

Immunostains revealed the following: LCA+, CD20+, CD79a+, BCL2+, Vimentin+. CD10-, CD30-, CD45RO-, Factor VIII-, CK20-, Synaptophysin-, Pancytokeratin-, CD34-. Peripheral CD3+, CD5+, and CD43+ represented reactive T cells to the lesional neoplastic cells.


Diffuse large B-cell non-Hodgkin's lymphoma, high grade

H&E

DIFFERENTIAL DIAGNOSIS:

1.   LyP
2.   Hodgkin's lymphoma
3.   Non- Hodgkin's lymphoma
4.   CTCL
5.   CD30+ Anaplastic Large Cell Lymphoma

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Diffuse large B-cell non-Hodgkin's lymphoma, high grade

DISCUSSION:

Primary cutaneous B-cell lymphomas are rare, making up the minority of primary cutaneous lymphomas. Classification schemes for cutaneous lymphomas have been controversial and continue to be disputed. Multiple classification schemes have been proposed, and have led to confusion in terminology of cutaneous lymphomas.

Cutaneous lymphomas typically present with erythematous to violaceous plaques and nodules on the skin. Primary versus secondary disease must be distinguished. Physical exam, laboratory workup, and imaging help to exclude systemic involvement. Patients may complain of fever, weight loss, night sweats, and fatigue. Lymphadenopathy, as well as hepatosplenomegaly, may be present, and an exam should also include lymph nodes and palpation of the liver and spleen.

Laboratory workup should include CBC, chemistries to evaluate liver and renal function, and LDH. Evaluation of systemic involvement should include a peripheral blood smear, bone marrow evaluation, CT or PET scan, and a lymph node biopsy if lymphadenopathy is found on exam.

Histology will reveal large, atypical lymphoid cells in a diffuse pattern of growth. These cells have hyperchromatic nuclei with prominent nucleoli. Mitoses may be abundant. Immunophenotype will stain positively for lymphoid markers, such as LCA (CD45), and B lymphocyte markers, such as CD20 and CD79a.

Low-grade, indolent B cell lymphomas do not require aggressive chemotherapy, and may be observed, and localized lesions may benefit from radiation therapy. Rituximab, an anti-CD20 antibody that targets CD20 on B cells, is generally used for low or high grade B-cell lymphomas. The standard treatment for aggressive, high-grade B-cell lymphomas include multiple-agent chemotherapy (CHOP) in combination with rituximab (CHOP-R), which may be followed by radiation.

TREATMENT:

CHOP chemotherapy with rituximab, followed by radiation.

REFERENCES:

1. Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP. Bosly A, Bron D, Van Hoof A, De Bock R, Berneman Z, Ferrant A, Kaufman L, Dauwe M, Verhoef G. Ann Hematol Oct 2007.
2. Treatment of primary cutaneous B-cell lymphoma with rituximab. Fink-Puches R., Wolf I.H., Zalaudek I., Kerl H., Cerroni L. J Am Acad Dermatol 2005; 52: 847-853.
3. Practical evaluation and management of cutaneous lymphoma. Maxwell A. Fung, Michael J. Murphy, Diane M. Hoss, Jane M. Grant-Kels. Journal of the American Academy of Dermatology. March 2002 (Vol. 46, Issue 3, Pages 325-357)
4. bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related. FA Geelen, MH Vermeer, CJ Meijer, SC Van der Putte, E Kerkhof, PM Kluin and R Willemze. Journal of Clinical Oncology, Vol 16, 2080-2085.
5. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Grange F, Beylot-Barry M, Courville P, Maubec E, Bagot M, Vergier B, Souteyrand P, Machet L, Dalac S, Esteve E, Templier I, Delaporte E, Avril MF, Robert C, Dalle S, Laroche L, Delaunay M, Joly P, Wechsler J, Petrella T. Arch Dermatol Sep 2007; 143(9):1144-50.
6. Lymphoma, B-Cell. Ajeet Gajra, MD, Neerja Vajpayee, MD, Sara Grethlein, MD. Last Emedicine. February 9, 2007.
7. Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma.
Heinzerling LM, Urbanek M, Funk JO, Peker S, Bleck O, Neuber K, Burg G, von Den Driesch P, Dummer R. Cancer Oct 2000; 89(8):1835-44
8. Primary cutaneous B-cell lymphoma in Japanese patients. Liu Q, Ohshima K, Kikuchi M. Pathol Int. Dec 2000; 50(12):960-6
9. Primary breast lymphoma in a patient with silicone breast implants: a case report and review of the literature. Newman MK, Zemmel NJ, Bandak AZ, Kaplan BJ. J Plast Reconstr Aesthet Surg. 2007 May 15.
10. Primary Cutaneous B-Cell Lymphoma: Review and Current Concepts By Tomi L. Pandolfino, Richard S. Siegel, Timothy M. Kuzel, Steven T. Rosen, Joan Guitart. Journal of Clinical Oncology, Vol 18, Issue 10 (May), 2000: 2152-2168.
11. Genetic Aberrations in Primary Cutaneous Large B-Cell Lymphoma: A Fluorescence In Situ Hybridization Study of 25 Cases. Wiesner, Thomas; Streubel, Berthold MD; Huber, Daniela; Kerl, Helmut MD; Chott, Andreas MD; Cerroni, Lorenzo MD. American Journal of Surgical Pathology. 29(5):666-673, May 2005.
12. WHO-EORTC classification for cutaneous lymphomas. Rein Willemze, et al. Blood, 15 May 2005, Vol. 105, No. 10, pp. 3768-3785.
13. Primary Cutaneous B-Cell Lymphoma: Review and Current Concepts. Tomi L. Pandolfino, Richard S. Siegel, Timothy M. Kuzel, Steven T. Rosen, Joan Guitart. Journal of Clinical Oncology, Vol 18, Issue 10 (May), 2000: 2152-2168.
14. The Cutaneous B-Cell Lymphoma Prognostic Index: A Novel Prognostic Index Derived From a Population-Based Registry. Benjamin D. Smith, Grace L. Smith, Dennis L. Cooper, Lynn D. Wilson. Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3390-3395.
15. An Illustrated Guide to Skin Lymphoma, 2nd ed. Lorenzo Cerroni, Kevin Gatter, and Helmut Kerl. Malden, Mass, Blackwell Publishing, 2004.

Additional Comment:

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