A 56-year-old Korean man visited our department in March 2009 with a 1-year history of multiple crusted erythematous masses on his face, neck, and left forearm (). The patient did not manifest any symptoms, such as, itching, pain, tenderness, fever, weight loss, or night sweats. In a previous visit to a community hospital in 2005, he had been diagnosed as having B cell type lymphoma based on the results of a surgical biopsy performed on an enlarged lymph node in his neck. Subsequently, he underwent 9 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone), which resulted in clinical remission. However, in 2008, small-sized reddish papules appeared on his face and grew in size with a firmer consistency than the original erythematous masses. New lesions also subsequently developed at other skin sites. His clinical differential diagnosis was indeterminate but skin metastasis or squamous cell carcinoma was suspected. A skin biopsy was then performed on a neck mass.
Variably sized multiple crusted erythematous masses on the face, neck (A & B), and Left forearm (C).
Histopathologically, basophilic tumor cells were found to infiltrate diffusely into the deep dermis without epidermal involvement. The small to medium sized round tumor cells contained vesicular nuclei, prominent nucleoli, and adopted a relatively monotonous appearance (). Immunohistochemically, the neoplastic cells were positive for CD3, CD4, CD5, UCHL-1, CD20, CD79a, and bcl-2 (). However, CD10, CD30, CD56, CD68, CD138, granzyme B, and EBV in situ were not expressed, although normal lymphocytes were positivite for CD8 and TIA-1.
Fig. 2 Diffuse and pandermal lymphocytic infiltration without epidermal involvement (A: H&E, ×40). The round tumor cells were small to medium sized with vesicular nuclei and prominent nucleoli and had a relatively monotonous appearance (B: H&E, (more ...)
Analysis of CD3 (A), CD4 (B), CD5 (C), UCHL-1 (D), CD20 (E), and for aCD79a (F) and bcl-2 (G) (immunoperoxidase stain, ×400).
Complete blood cell count, differential cell count, urinalysis, and liver function testing (including BUN/Cr) were normal as well as peripheral blood smear and a bone marrow biopsy were also normal. Computerized tomography revealed multiple enlarged tumor masses on the neck with lymphadenopathies on the interjugular, submandibular, and submental lymph nodes.
We determine the nature of this case, where both T and B cell associated antigens were expressed, by performing multiplex PCR studies to assess the rearrangement of T cell receptor (TCR) gamma and immunoglobulin heavy chain (IgH). In addition, we histopathologically reviewed the biopsy specimen taken in 2005 from a neck lymph node, and subjected it to immunophenotypic and genotypic analysis.
For the genotypic analysis, 35 cycles of two multiplex PCR reactions were performed for TCR gamma gene rearrangements on the DNA extracted from 8 µm sections that were deparaffinized. The primers used in Mix 1 PCR were: V2(5'-CTT-CCT-GCA-GAT-GAC-TCC-TAC-AAC-TCC-AAG-GTT G-3'), V3(5'-CTT-CCT-GCA-GAT-GAC-GTC-TCC-ACC-GCA-AGG-GAT-G-3'), V4(5'-CTT-CCT-GCA-GAT-GAC-TCC-TAC-ACC-TCC-AGC-GTT-G-3'), V8(5'-CTT-CCT-GCA-GAT-GAC-TCC-TAC-AAC-TCC-AGG-GTT-G-3'), V9(5'-GGN-ACT-GCA-GGA-AAG-GAA-TCT-GGC-ATT-CCG-3'), JGT12(5'-AAG-TGT-TGT-TCC-ACT-GCC-AAA-3'), JGT3 (5'-AGT-TAC-TAT-GAC-CTA-GTC-CC-3'), JGT4(5'-TGT-AAT-GAT-AAG-CTT-TGT-TCC-3'). The primers used in the Mix 2 PCR were: V5(5'-TTC-CTG-CAG-ATG-ACG-TCT-CCA-ACT-CAA-AGG-ATG-3'), V10(5'-CTC-TGC-AGA-ATC-CGC-AGC-TCG-ACG-CAG-CA-3'), V11(5'-CAC-TGC-AGG-CTC-AAG-ATT-GCT-CAG-GTG-GG-3'), V12(5'-ACT-CTG-CAG-CCT-CTT-GGG-CAC-TGC-TCT-AAA-3') and the same three joining primers. Jurkat cells were used as positive controls and a previous negative sample was used as a negative control. Thirty-five cycles of semi-nested PCR for the FRIII-J segment were conducted for IgH gene rearrangements, using the primers FRIIIA(5'-ACA-CGG-CYS-TGT-ATT-ACT-GT-3'), LJH(5'-TGA-GGA-GAC-GGT-GAC-C-3'), and VLJH(5'-GTG-ACC-AGG-GTN-CCT-TGG-CCC-CAG-3'). The semi-nested first primers were FRIIIA and LJH and the second primers were FRIIIA, VLJH. RAJI cells were used as positive controls and a previous negative sample was used as a negative control. The TCR gamma gene rearrangement showed monoclonality at around 200bp in our and the previous biopsy specimens, but the IgH gene rearrangement showed no monoclonality in either specimen ().
T cell receptor gamma gene rearrangement showed monoclononality at around 200 bp in the present and previous biopsy specimens (A, B), but immunoglobulin heavy chain gene rearrangement showed no monoclonality in either specimen (C, D).
Histopathologic findings of the neck lymph node biopsy performed in 2005 revealed the presence of basophilic small to medium sized tumor cells infiltrating in a diffuse manner that sometimes formed multiple nodules and effacement of the normal architecture, which resembled that observed in our skin specimen. The immunophenotypic evaluation was strongly positive for CD20 and weakly reactive to UCHL-1 in the cytoplasm of atypical lymphocytes (). In addition, neoplastic cells were found to be positive for CD3 and CD4 and negative for CD30 ().
The immunophenotypic evaluation performed on a neck lymph node excised at the biopsy performed in 2005, was strongly positive for CD20 (A, ×400) and weakly reactive with UCHL-1 (B, ×400) in the cytoplasm of atypical lymphocytes.
Immunophenotypic evaluation from a neck lymph node excised in 2005 was positive for CD3 (A, ×400) and CD4 (B, ×400) and negative for CD30 (C, ×400).
All these findings were compatible with CD20 positive peripheral T cell lymphoma. Supposedly, the disease had recurred in the skin from systemic disease or metastasized from nodal disease. The patient was treated with ifosfamide, methotrexate, VP-16 (etoposide), and prednisolone chemotherapy regimen and showed partial remission and reduction in mass size ().
The patient underwent ifosfamide, methotrexate, VP-16 (etoposide), and prednisolone chemotherapy and achieved partial remission with a decrease in mass size (A & B: face, neck, C: Left forearm).