Peripheral T-Cell Lymphoma not Otherwise Specified, Two Years after Oesophageal Cancer: A Case Report

Sir, To the Editor: Peripheral T-cell lymphoma (PTCL) is a type of lymphoma that originates in T cells and migrates to peripheral organs. There are three main types of PTCL: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large-cell lymphoma (ALCL).1 Here, we describe one patient diagnosed with PTCL-NOS who had suffered from oesophageal cancer 2 years ago. A 70-year-old man was admitted to our department on 10 July 2020 presenting with erythema, ulcer, fever, pneumonia and weight loss. He had oesophageal cancer in May 2018, and a total esophagectomy was successfully performed using video-assisted thoracoscopic surgery. He did not receive chemotherapy or radiotherapy after that surgery. No recurrence of oesophageal cancer was found during these 2 years. Several red plaques and many pigmented erythemas of different sizes were found on his trunk and limbs Figure 1a. Two infiltrated plaques were observed on the right shoulder and right chest Figure 1b. Ulceration could be seen at the edge of the erythemas on his left chest, and one of the ulcers was about 1.5 × 3 cm in size Figure 1c. There was no tenderness on palpation.Figure 1: Pigmented erythema on the patient's trunk and limbs (a). Infiltrated plaques on the right shoulder and right chest (b). Ulcerated lesion sized 1.5 × 3 cm2 on the patient's left chest (c)Laboratory data showed decreased levels of leucocytes (2.73 × 109/L), erythrocytes (3.66 × 109/L), lymphocytes (0.48 × 109/L) and increased lactate dehydrogenase (601 u/l) and ferritin (>1500.0 ng/ml). The results of serum tumour index markers showed increases of CA15-3 (33.41 U/ml), CA125 (39.15 U/ml) and CEA (5.36 ng/ml). A whole-body positron emission tomography (PET)/computed tomography (CT) scan revealed an abnormal increase of FDG metabolism in multiple lymph nodes in the mediastinum, bilateral hilar, retroperitoneal, abdominal mesenteric area, right side of iliac vessels, right inguinal area, and multiple subcutaneous, muscle and intramuscular areas. A skin biopsy specimen showed complete effacement of the architecture by typical medium- to large-sized lymphocytes, some with abundant clear cytoplasm and forming vague modularity as well as extensive necrosis. The histopathology findings were consistent with PTCL Figure 2. Immunohistochemical staining of tumour cells was positive for CD2, CD8, granzyme B, TIA-1 and Ki-67, weakly positive for CD4 and negative for CD20, CD56 and CD30 Figure 3. Clonal pathological rearrangements of the T-cell receptor (TCR) gene were TCRG:A(-)B(-), TCRB:A(-)B(-)C(+), TCRD:(-). The results of a bone marrow biopsy showed that the proliferation of nucleated cells was decreased. Epstein–Barr virus (EBV)-specific antibody serology testing was performed and showed high levels of viral capsid antigen (VCA) and Epstein–Barr virus nuclear antigen (EBNA) IgG antibodies. Based on the histological and immunohistochemical findings, the diagnosis was confirmed as primary PTCL-NOS and the patient was transferred to the Hematology Department for further treatment.Figure 2: Medium to large tumour cells that infiltrated into subcutaneous adipose tissue, with irregular nuclei and clear cytoplasm (haematoxylin–eosin stain, magnification ×400)Figure 3: Immunohistochemical staining showing that (a) CD2, (b) CD8, (c) granzyme B, (d) TIA-1 and (e) Ki-67 positive, (f) CD4 weakly positive, and (g) CD20, (h) CD56 and (i) CD30 were negative (magnification ×200)The patient then underwent treatment with two cycles of chemotherapy (CHOP therapy: CTX (1.2 g day 1), THP (60 mg day 1), DXM (10 mg days 1–5) and orelbine bitartrate (30 mg day 1)). He was then discharged from the hospital with obvious improvement of his chest ulcer and plaque, but he still had a low fever. But only 2 months later, he returned to the Hematology Department because of rash recurrence, cachexia and high fever. The patient withdrew from further treatment because of the rapid deterioration of his condition finally. PTCL-NOS is an exclusive diagnosis. The pathogenesis remains unknown. Cutaneous PTCL-NOS is rare, accounting for less than 2% of CTCL, and can involve the skin primarily or secondarily,2 which might appear as a primary cutaneous disease or as a part of systemic lymphoma. Other common extranodal sites are the liver, bone marrow, spleen, lungs and gastrointestinal tract.3,4 PTCL-NOS has certain clinicopathological characteristics such as adult onset, frequent CD4 and CD8 expression and an aggressive clinical behaviour. PTCL-NOS has a high incidence in Asia by comparison and accounts for about 10% of all non-Hodgkin's lymphoma. Further, age >60 years old, physical condition grade 2–4, high expression of Ki-67, increased serum LDH and Epstein–Barr virus (EBV) may be poor prognostic factors.5 In this case, granzyme B was co-expressed, and expression levels of Ki-67 and VCA and EBNA IgG antibodies were high, which was related to a severe clinical course, particularly in the sudden exacerbation. The patient had typical clinical manifestations including bulky lymphadenopathy, extranodal disease, systemic constitutional symptoms (fever, night sweats and weight loss) and elevated levels of lactate dehydrogenase. A biopsy of the ulceration at the edge of erythemas supported the diagnosis. Interestingly, the dark-brown granules evident by CD4 immunohistochemical staining were mostly found in normal lymphocytes and less in tumour cells; so, it was judged to be weakly positive for CD4 by the pathologist, which was a little different from the general immunohistochemical staining of lymphoma. Combined with the results of PET-CT, bone marrow puncture and biopsy, the diagnosis of PTCL-NOS was established.6 PTCL-NOS is associated with certain genetic mutations. The patient's clonal pathological rearrangements of the TCR gene were TCRG: A(-)B(-), TCRB: A(-)B(-)C(+), TCRD:(-). This is a rare case of PTCL-NOS that occurred 2 years after surgery for oesophageal cancer. It has been reported that total body irradiation, immunosuppressants and chronic GVHD are associated with a risk of secondary malignancies,7-9 but the patient did not receive chemotherapy or radiotherapy after his oesophageal cancer surgery. It is not clear that the two diseases are definitely related, maybe the abnormal immune state after resection of the tumour is one risk factor for PTCL-NOS. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.