Abstract
Primary cutaneous lymphoma is a heterogeneous group of cutaneous lymphocytic primary tumors belonging to the extranodal category of non-Hodgkin lymphoma. Skin is the second most common site of extranodal non-Hodgkin lymphoma after the gastrointestinal tract. Skin lesions are the main manifestations of primary cutaneous lymphoma. Here, we report two successful cases of skin ulcers caused by primary cutaneous lymphoma, which is both rare and difficult to diagnose. One case involved primary cutaneous T-cell lymphoma, and the other involved primary cutaneous B-cell lymphoma. Systemic antitumor therapy combined with the right local wound management is the key to ulcer healing. For wound management, in addition to infection control, exudate management, pain control, and odor management, evaluation and intervention of debridement are worthy of consideration, but they must be evaluated by an expert group, and plans must be made for bleeding. Finally, the wounds of the two patients were completely healed after 79 and 65 days under active systemic therapy.
Introduction
Primary cutaneous lymphoma (PCL) is a heterogeneous group of cutaneous lymphocytic primary tumors belonging to the extranodal category of non-Hodgkin lymphoma. Skin is the second most common site of extranodular non-Hodgkin lymphoma after the gastrointestinal tract. 1 With an incidence of 1/100,000 per year, extranodular non-Hodgkin lymphoma primarily proliferates in the skin and has no evidence of extracutaneous involvement at the time of diagnosis. 2 Therefore, newly diagnosed patients are often treated for skin ulcers. Moreover, the early clinical manifestations lack specificity, and diagnosis is difficult. 2 The average duration of disease before diagnosis has been reported to be 41.27 months. 3
PCL can be divided into two groups based on the origin of tumor cells: cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL). 4 CTCL includes more than 10 subtypes, mainly including the mycosis fungoides (MF), Sezary syndrome (SS), and primary cutaneous. CD30-positive T-cell lymphoproliferative disease accounts for 90%. Primary cutaneous CD30-positive lymphoproliferative diseases include lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (PC- ALCL).2,5,6
CBCL mainly includes primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma (leg type) (PCDLBCL (LT)).
Due to the low incidence of PCL, most of the existing research is related to drug treatments for diseases, while few studies have focused on the management of ulcers caused by lymphoma. However, as the first and main symptom of PCL, early identification and treatment of skin ulcers should receive more attention. In this report, we present the clinical characteristics and successful handling experience of two cases of PCL-associated ulcers, with the aim to provide a reference for peers. One case was PC-ALCL and the other was PCDLBCL (LT). Informed consent was obtained from the patient prior to the publication of this case report and all associated images.
Case presentation
Case 1
A 51-year-old female patient complained of right groin mass ulceration with pain for more than a month and presented to the Wound Care Center (WCC) of Nanjing Drum Tower Hospital on November 1, 2022. Her previous history included “mass resection of the left thigh root” 3 years prior and a history of syphilis, hypertension, and venous thromboembolism.
The biopsy results of the right inguinal lymph node showed a malignant, poorly differentiated tumor, combined with immunohistochemical results consistent with PC-ALCL. Pathological images are shown in Figure 1(a) and (b). Bone marrow cytology showed the presence of bone marrow hyperplasia, granulocytes, red blood cells, and megakaryocyte hyperplasia. The patient was diagnosed with ALCL. Three chemotherapy sessions were conducted on November 10, 2022, December 6, 2022, and January 16, 2023. The chemotherapy regimen was brentuximab plus the CHP regimen (brentuximab 100 mg on day 0, cyclophosphamide 1.2 g, epirubicin 100 mg on day 1, prednisone acetate 100 mg from days 1 to 5). After three rounds of chemotherapy, the patient’s condition improved and the treatment was completed.
The pathological images of the two cases. (a) Hematoxylin-eosin (HE) staining of case 1: the tumor cells are large, presenting an epithelial or histiocyte-like appearance. The nuclei are round, horseshoe-shaped, kidney-shaped, or embryonic-like, at 400× magnification. (b) The immunohistochemical staining of case 1: the tumor cells expressed ALK in a diffuse positive manner, at 200× magnification. (c) HE staining of case 2: abnormally differentiated lymphocytes show diffuse infiltrative growth, involving adipose tissue, at 400× magnification. (d) Immunohistochemical staining for case 2: the tumor cells showed diffuse positive expression of Ki67, at 200× magnification.
Wound assessment was based on the “Triangle of Wound Assessment.” 7 At the first visit, the mass was 7 × 10 cm in size, with a large amount of yellow exudate and redness of the skin around the mass (Figure 2(a)). The wound was rated odor grade 2 (odor can be detected at less than arm’s length) on an odor assessment scale, 8 with obvious signs of infection, including local redness, high skin temperature, increased fluid leakage, increased pain, and a distinct odor. The wound edge was red and swollen, and the epidermis was exfoliated. The skin around the wound was hard and swollen. The patient’s visual analogue scale pain score 9 was 6.
First stage of the wound treatment process in case 1. (a) Initial wound assessment. (b) Anti-infection dressing on wound. (c) Bandage fixation.
After a thorough wound assessment, the wound specialists developed a three-step wound care plan based on wound management principles. 10 The first stage was to manage the exudate, reduce odor, control infection, and relieve pain; the second stage was local, careful debridement and infection control; and the third stage was granulation protection and epithelial promotion. Specific measures in the first stage include the following: disinfection of wounds with 0.5% iodophor and clamping of loose rotting flesh; washing and drying with normal saline; covering with silver zirconium phosphate alginate dressing (Biatain® Alginate Ag; Coloplast, Peterborough, England) to absorb seepage and resist infection (Figure 2(b)); and application of a sterile cotton pad and elastic bandage (Figure 2(c)). The patient’s reported pain score decreased to 4.
By November 21, 2022, due to ineffective control of lymphoma, the wound had developed to 100% necrotic tissue and increased fluid seepage. The second stage of intervention was initiated, including the following: The infection was controlled by a wet compress with a liquid dressing (Prontosan®; B. Braun, Sempach, Switzerland) for 15 min; sterile scissors were used to carefully remove part of the necrotic tissue to avoid bleeding and damage to normal tissue (Figure 3(a)–(d)); 30 min before debridement, the patient took ibuprofen painkiller orally to reduce the pain caused by debridement; the dressing coated with silver alginate zirconium sodium phosphate was hemostatic, absorbent fluid, and anti-infection; the skin protective film was applied to the surrounding skin to prevent excessive infiltration of the surrounding skin; and a sterile cotton pad and elastic bandage was applied. The patient’s reported pain score decreased to 1.
Second stage of the wound treatment process in case 1. (a) Massive necrotic tissue. (b–d) Step-by-step debridement.
By December 9, 2022, the wound had 100% granulation tissue, and the size was reduced to 3.5 × 5 cm (Figure 4(a)). The wound continued to shrink (Figure 4(b)), moving into the third stage of the process. Silver sulfate lipid hydrocolloid dressing (Laboratoires URGO S.A., Chenôve, France) was used to prevent adhesion and promote epithelialization, and the wound was completely healed on January 18, 2023 (Figure 4(c)).
Third stage of the wound treatment process in case 1. (a–c) The wound shrinks until it heals.
The patient’s health education included lower limb elevation and ankle pump exercises to promote reflux; appropriate getting out of bed activities; promoting a low-salt, low-fat, vitamin-rich, high-protein diet, with more fruits, vegetables, and other crude fiber foods; drinking more water; and communicating effectively with the patient to relieve her psychological burden.
Case 2
A 39-year-old man with recurrent diffuse large B-cell lymphoma was admitted to the dermatology department in March 2024 due to multiple red papules in the right groin for more than 1 week. The doctor recommended Halomethasone cream and Luliconazole cream for external use, but the effect was poor. As of May 2024, the pathological findings were consistent with PCDLBCL. Pathological images are shown in Figure 1(c) and (d). On July 1, 2024, the patient was admitted to the WCC to seek further wound treatment. At the same time, after being evaluated by hematologists, the patient met the clinical trial criteria and was administered the intravenous clinical trial drug TQB2825.11,12 The patient received treatment with rituximab at a dose of 375 mg/m2 on June 21, 2024. On June 24, they were administered TQB2825 at 0.3 mg, on July 2, they were given TQB2825 at 1 mg, and on July 9 and July 23, they received 50 mg (the full dose) of the medication. After four courses of treatment, the efficacy of the disease was evaluated and found to be partially effective.
During the initial visit, multiple masses could be seen in the left and right groins. There were two wounds on the left mass, with 75% yellow and 25% red tissues, a large amount of purulent exudate, increased skin temperature, and obvious signs of infection (Figure 5(a)). The measures taken included two stages. The first stage was local careful debridement, infection control, and exudate management; and the second stage protected the granulation and promoted epithelial growth.
First stage of the wound treatment process in case 2. (a) Initial wound assessment. (b) Wet application of a liquid dressing on the wound. (c) Anti-infection dressing on the wound. (d) Wound after debridement.
The specific measures of the first stage included iodophor disinfection of the local wound and surrounding skin; wet application of a liquid dressing (Prontosan®; B. Braun) for 15 min to control infection and reduce odor; use of sterile scissors to gradually remove loose necrotic tissue; filling with silver zirconium phosphate alginate dressing (Biatain® Alginate Ag; Coloplast); and cover with gauze and cotton pad, before fixing with a bandage (Figure 5(b)–(d)). The patient took an ibuprofen painkiller orally 30 min before debridement to reduce the pain caused by debridement.
In the second stage, the wound and seepage were reduced. Silver sulfate lipid hydrocolloid dressing (Laboratoires URGO S.A.) was used to prevent adhesion and promote epithelialization. On September 3, 2024, the groin mass disappeared, and the wound healed completely (Figure 6(a)–(c)). On March 14, 2025, through a telephone follow-up, there was no lymph node swelling or rupture, and the patient’s quality of life was good.
Second stage of the wound treatment process in case 2. (a) Shrinking of the groin mass. (b) Anti-infection dressing on wound. (c) The groin mass disappeared and the wound healed.
Discussion
The incidences and clinical features of PCL tend to differ by age, sex, geographical, and racial variation.13,14 An Italian 5-year retrospective study (2017–2022) 15 of 100 patients with PCL showed that the mean (SD) age of the cohort was 70.33 (14.14) years. CTCL represented 65% of all cases; the majority were MF (42%), followed by cases of SS (10%) and PC-ALCL (4%). CBCL accounted for 35% of PCL cases, with 15 cases of PCFCL, 10 cases of PCDLBCL (LT), and nine cases of PCMZL. In a Korean study, 16 627 cases of PCL diagnosed between 1994 and 2022 were included. Most PCL cases (87.2%) involved CTCL, whereas the remaining cases (12.8%) involved CBCL. The prevalence of MF in CTCL increased significantly over time, whereas the frequency of other CTCL subtypes decreased. A study of 72 patients with PCL in China showed similar results to those of CTCL (86.11%) and CBCL (13.89%). The mean age at onset was 54.40 ± 12.63 years. The shortest disease course was 0.5 months, the longest was 30 years, the average course of disease before diagnosis was 41.27 months, and the average course of disease of MF was 55.98 months. 3 Prolonged failure to diagnose or misdiagnose results in a delay of the optimal treatment time and affects the prognosis of patients. Patients with these conditions are often treated for common ulcers, and they are usually treated for herpes and eczema at first diagnosis. As a professional wound nurse, when there is no progress in the wound after 2–4 weeks of standardized treatment, the patient should take into account whether there are atypical causes, such as immune system diseases and lymphoma, and should recommend timely pathological examination to identify the cause.
The management of primary lymphoma-associated ulcers focuses on a combination of systemic treatment for lymphoma and local wound treatment. Both patients in our case received effective systemic antitumor therapy, which led to the reduction and eventual disappearance of the mass and the recovery of systemic hematological indicators, which is an important prerequisite for wound healing. For local wounds, primary lymphoma-associated ulcers meet the common characteristics of malignant wounds: bleeding, odor, pain, excessive exudate, and infection.17,18 The treatment of malignant wounds is based on symptom management: managing exudate, controlling infection, preventing bleeding, reducing pain, and reducing odor. Due to the risk of bleeding from malignant wounds and the fact that some patients are at the end of life, debridement intervention is not routinely recommended, even though a large amount of necrotic tissue seriously affects wound healing and quality of life. However, these two cases were relatively young, had good basic conditions, and were expected to have a good prognosis with systemic antitumor therapy.
After evaluation by the surgical and wound expert group, the slough and deactivated tissue on the wound were progressively debrided. During debridement, the surgeon worked together at the bed with the wound specialist, while a large number of cotton pads were prepared at the bedside, and the electrocoagulation knife was on standby for emergency hemostasis in case of bleeding. The wounds of the two patients were completely healed after 79 and 65 days under active systemic therapy.
Conclusions
Here, we reported two successful cases of skin ulcers caused by PCL, which were both rare and challenging to diagnose. Based on these findings, we would like to remind colleagues that early identification and diagnosis of such ulcers are essential. After diagnosis, systemic treatment combined with local wound management was important for ulcer healing. Based on an accurate evaluation, careful debridement may also be an effective wound management strategy, but this strategy must be prepared for the emergency management of bleeding.
Footnotes
Ethical considerations
Our institution does not require ethical approval for reporting individual cases or case series.
Consent for publication
Written informed consent was obtained from the patient(s) for their anonymized information to be published in this article.
Funding
This study was funded by: Aid project of Jiangsu Ningai Medical Development & Medical Aid Foundation(NDYGN2024074)
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.