Analysis of anxiety and depression and influencing factors in non-Hodgkin's lymphoma of the nasal cavity and paranasal sinus

Abstract

BACKGROUND

Natural killer (NK)/T-cell non-Hodgkin's lymphoma (NHL) in the nasal cavities and paranasal sinuses accounts for approximately 10% of all lymphomas, and the occurrence of nasal NHL is related to Epstein-Barr virus infection.

AIM

To explore the anxiety and depression status of patients with NK/T-cell NHL in the nasal cavities and paranasal sinuses and analyzes the relevant influencing factors.

METHODS

A retrospective analysis was performed, which included 30 patients with primary nasal NK/T-cell NHL treated in Shaanxi Provincial People’s Hospital from January 2017 to January 2023. An additional 50 healthy volunteers were selected as the control group. Both groups were assessed using the self-rating anxiety scale (SAS) and Self-rating (SDS). SDS and SAS scores of patients with NHL at different disease stages were analyzed, and they were further grouped into negative emotion (NE) (n = 19) and non-NE (n = 11) groups based on their depression and anxiety. Factors affecting the occurrence of NEs in patients with NHL were analyzed using univariate and multivariate logistic regression models.

RESULTS

Patients with NHL exhibited higher SDS and SAS scores than healthy controls. Moreover, patients with NHL at stages III and IV had higher SDS and SAS scores than those in stage I. Among the 30 patients, there were 13 patients with depression (43.3%), 16 patients with anxiety (53.3%), and 10 patients with both anxiety and depression (33.3%). Univariate analysis identified a higher proportion of people in the NE group with stage III-IV NHL, an educational level ≤ high school, and a monthly household income < 5000 yuan compared with the non-NE group. Multiple logistic regression analysis further revealed that stage III-IV was a risk factor for NEs in patients with NHL.

CONCLUSION

The stage of NK/T-cell NHL in nasal cavities and paranasal sinuses is closely related to patient anxiety and depression. The higher the staging, the greater the incidence of anxiety and depression.

Key Words: Nasal cavities and paranasal sinuses; Natural killer/T-cells; Non-Hodgkin's lymphoma; Anxiety; Depression

Core Tip: Nasal natural killer (NK)/T-cell lymphoma is a rare disease that typically exhibits a highly aggressive clinical course. Its treatment is limited, mainly consisting of radiation or combined chemotherapy. As a negative stress event, lymphoma has a great effect on patients’ psychological status, family life, economy, and other aspects. Therefore, in clinical practice, the psychological well-being as well as changes in the physiological function of patients with cancer should be monitored. This study primarily analyzed the anxiety and depression status of patients with NK/T-cell non-Hodgkin's lymphoma in the nasal cavities and sinuses to understand their psychological health status.

INTRODUCTION

Natural killer/T-cell lymphoma (NKTL) is a rare lymphocytic malignancy that mainly involves extranodal nodules, which usually originates from natural killer (NK) cells and (rarely) T-cells and is closely related to Epstein-Barr virus (EBV) infection[1,2]. This lymphoma has a low incidence in the United States and Europe, accounting for only 0.2%-0.4% of newly diagnosed cases of non-Hodgkin's lymphoma (NHL)[3,4], compared to 5%-15% in Asia, Central America, and South America, where it is more common[5]. The most common site is the nasopharynx, followed by the sinus, tonsil, Waldeyer's ring, and oropharynx[6]. Nasal NK/T-cell lymphoma is a rare disease that typically exhibits a highly aggressive clinical course[7]. Nasal NK/T-cell lymphoma, formerly known as midline lethal granuloma or angiocentric T-cell lymphoma, involves the upper digestive tract of the nasal cavity, nasopharynx, sinuses, tonsils, or palate[8,9]. The prognosis is poor, with a five-year overall survival rate of only 50% in the early clinical stage[10,11]. Nasal NK/T-cell lymphoma has a high predilection for males, typically in their 40s or 50s at the time of diagnosis, which is slightly lower than other lymphoma types[12]. In addition, lymphomas involving the nasal cavity in the initial stages are often misdiagnosed as inflammatory sinus disease and are detected only after progression. As a result, most cases are diagnosed later and have a high mortality rate.

NK/T-cell lymphoma cells express multidrug resistance 1 (MDR-1) and its gene product P-glycoprotein[13]. EBV-infected NK/T-cells are intrinsically resistant to apoptosis because of the overexpression of the anti-apoptotic molecules BCL-XL and MCL-1. Modern chemotherapeutic regimens use drugs that are not affected by MDR-1, such as etoposide or ifosfamide[14]. NK/T-cell lymphomas are sensitive to radiotherapy (RT), which is usually given at doses greater than 50 Gy, and abandoning RT early in the disease results in a poor prognosis[15]. Because of their glutamine addiction, NK/T-cell lymphomas are susceptible to asparagine depletion, which triggers apoptosis, thus providing the rationale for adding asparaginase to treatment regimens[16]. Data from retrospective studies have suggested that RT alone is an effective treatment for early-stage NKTL, whereas combination chemotherapy provides no benefit[17]. Furthermore, there is consensus that patients with advanced NKTL benefit from combined radiation and chemotherapy. For example, in a study using an intermediate/high-risk cohort of neoadjuvant response index patients, the 5-year survival rates for combined radiation and chemotherapy were approximately 75% and 60%, respectively, compared with radiation therapy alone[18,19].

With the prominence of the biopsychosocial medical model, cancer is considered a psychosomatic disease[20]. In recent years, concern for patients with malignancies has no longer been limited to physical complaints but extended to their mental health status, with increasing research and literature reports in this area and certain results achieved. As a negative stress event, lymphoma has a substantial impact on patients’ psychological status, family life, economy, and other aspects. Lymphoma has a long treatment cycle, recurrent conditions, and easy recurrence. The long-term systemic compression symptoms and chemotherapy-induced nausea, vomiting, hair loss, physical weakness, and myelosuppression result in emaciation, decreased appetite, and fatigue, which brings great pain to patients and can easily lead to negative emotions (NEs)[21,22]. Patients with rare cancers are affected by symptoms, toxic side effects of chemotherapy, and other factors that are often accompanied by anxiety, depression, and other NEs, leading to an increase in the degree of psychological pain, which is not conducive to treatment compliance and threatens the patient's quality of life[23]. Therefore, in clinical practice, it is necessary to keep abreast of the changes in the physiological function of patients with cancer as well as their psychological state and to provide targeted intervention and treatment in time to improve the prognosis. Accordingly, this study mainly analyzed the anxiety and depression status of patients with NK/T-cell NHL in the nasal cavities and sinuses to understand their psychological health status and whether there are differences among patients of different ages, genders, disease courses, medical insurance types, and stages, and to analyze the factors that influence NEs in these patients.

MATERIALS AND METHODS

Research population

Thirty cases of patients with primary nasal NK/T-cell NHL treated in Shaanxi Provincial People’s Hospital from January 2017 to January 2023 were retrospectively enrolled for analysis. Inclusion criteria: (1) NK/T-cell surface antigens CD45RO(+) and CD56(+) were confirmed by pathomorphology and immunoenzyme histochemical detection; (2) Initial clinical symptoms were nose-associated; (3) No history of mental illness; and (4) Basic hospitalization data and clinical records were relatively complete. Exclusion criteria: (1) No access to accurate pathological reports; (2) Primary tumors in other areas or other life-threatening diseases, such as serious diseases of the heart, liver, kidneys, and hematopoietic system; and (3) History of mental illness and central nervous system diseases and an unwillingness to cooperate with treatment. A further 50 healthy volunteers from the same period were selected as the control group, and the exclusion criteria were the same as those for patients with NHL.

Patient data collection

The general information survey form was designed by our hospital and included the patient's name, gender, age, marital status, education level, payment method of medical expenses, course of the disease, efficacy evaluation, past medical history and pathological types, clinical staging, etc. Clinical staging was assessed according to the Ann Arbor staging system[24]: Stage I: Invasion of a lymph node area (stage I) or invasion of an extranodal organ or site (IE). Stage II: Invasion of two or more lymph nodes on one side of the diaphragm (II), or invasion of an extranodal organ combined with invasion of one or more lymph nodes ipsilateral to the diaphragm (IIE). Stage III: Lymph node invasion on both sides of the diaphragm (III), which may be combined with a local extranodal organ or invasion site (IIIE) or complicated with spleen invasion (IIIS) or extranodal organs plus spleen invasion (IIIE + S). Stage IV: Concomitant invasion of one or more distant extranodal organs.

Psychological state assessment

Questionnaire surveys were performed on the day of physical examination of healthy volunteers and within 3 days of the patients’ definitive diagnosis. The self-rating anxiety scale (SAS) and Self-rating depression scale (SDS) were used to evaluate the patient's degree of anxiety and depression. They were required to complete the questionnaire themselves within 20-30 minutes. Those with poor eyesight and less education had the questionnaire read to them by a trained professional without any hints or bias, and then they made the choice. SAS score: This tool includes 20 items, such as nervous, fear of the worst happening, hand and leg trembling, dizziness, hyperhidrosis, and akathisia; with 50 as the boundary, a SAS score of < 50 suggests no anxiety, while a score of 50-62, 63-72, and ≥ 73 is considered mild, moderate, and severe anxiety, respectively. SDS score: This questionnaire has 20 items, such as loss of appetite, down-hearted and blue, palpitations, restlessness, irritability, decreased ability, sense of emptiness in life, loss of interest, with 1-4 points for positively worded questions and 4-1 points for negatively worded questions; with 53 as the boundary, < 53 indicates no depression, while 53-62, 63-72, and ≥ 73 suggests mild, moderate, and severe depression, respectively.

Statistical analysis

The obtained data were processed using SPSS 25.0. Continuous data were expressed as the mean ± SD, and comparisons were made using the t-test (within groups) and one-way ANOVA (among groups). Categorical data were expressed as percentages, and χ² tests were used for comparisons. Logistic regression analysis was performed to analyze the influencing factors of anxiety and depression in patients. P < 0.05 was established as the significance threshold.

RESULTS

General data

As shown in Table 1, patients with NHL and healthy controls exhibited no marked difference in sex, age, body mass index, education level, and other general data (P > 0.05), thus indicating comparability.

Table 1 Comparison of general data between non-Hodgkin's lymphoma patients and controls.

	NHL (n = 30)	Control (n = 50)	χ2/t	P value
Gender			0.086	0.769
Male	17	30
Female	13	20
Age (years)	52.43 ± 5.92	54.30 ± 6.35	1.305	0.196
BMI (kg/m2)	21.40 ± 2.22	21.81 ± 2.02	0.859	0.393
Course of disease	0.99 ± 0.38	-
Education level			0.274	0.600
High school and below	18	27
Bachelor degree or above	12	23
History of smoking	11	26	1.773	0.183
History of drinking	12	29	2.432	0.119
Marital status			0.126	0.939
Married	16	28
Single	7	10
Others	7	12

NHL: Non-Hodgkin's lymphoma; BMI: Body mass index.

SDS and SAS scores

As shown by Table 2, the SDS score of patients with NHL was 52.73 ± 6.02 and the SAS score was 50.17 ± 6.80, which were significantly higher than the SDS (39.56 ± 4.91) and SAS (37.85 ± 4.88) scores of the control volunteers (P < 0.05). These results suggest that patients with NHL are more likely to experience anxiety and depression relative to the control volunteers.

Table 2 Comparison of self-rating depression scale and self-rating anxiety scale scores.

	SDS	SAS
NHL (n = 30)	52.73 ± 6.02	50.17 ± 6.80
Control (n = 50)	39.56 ± 4.91	37.85 ± 4.88
t	10.660	9.607
P value	< 0.001	< 0.001

SAS: Self-rating anxiety scale; SDS: Self-rating depression scale; NHL: Non-Hodgkin's lymphoma.

SDS and SAS scores of patients with different disease stages

The SDS and SAS scores of patients with NHL gradually increased as the disease staging progressed, and the intergroup differences were statistically significant. Specifically, patients with stages III and IV NHL had higher SDS (53.70 ± 6.40 and 58.50 ± 6.56, respectively) and SAS (54.10 ± 3.78 and 55.75 ± 8.92, respectively) scores than those with stage I NHL (P < 0.05), while the SDS and SAS scores were not statistically different between patients with stage III and IV NHL (P > 0.05) (Table 3). These results indicate that patients with higher disease stages have higher levels of depression and anxiety.

Table 3 Comparison of self-depression scale and self-rating anxiety scale scores in patients with different stages.

Stage	SDS	SAS
I (n = 8)	48.38 ± 3.66	44.13 ± 4.91
II (n = 8)	53.00 ± 4.87	48.50 ± 5.50
III (n = 10)	53.70 ± 6.40	54.10 ± 3.78
IV (n = 4)	58.50 ± 6.56	55.75 ± 8.92
F	3.376	6.873
P value	0.033	0.002

SAS: Self-rating anxiety scale; SDS: Self-rating depression scale.

Univariate analysis of the influencing factors of patients’ NEs

Among the 30 patients, 13 (43.3%) experienced depression, 16 (53.3%) developed anxiety, and 10 (33.3%) suffered from both anxiety and depression. According to the occurrence of anxiety or depression, there were 19 patients with NEs and 11 without. The proportion of patients with stage III-IV illness, education level at high school or below, and a monthly household income < 5000 yuan was higher in the NE group than in the non-NE group (P < 0.05). However, no significant intergroup differences were found in gender, age, body mass index, smoking history, drinking history, and marital status (P > 0.05) (Table 4).

Table 4 Univariate analysis of influencing factors of patients' negative emotions.

	Negative emotions (n = 19)	Non-negative emotions (n = 11)	χ2/t	P value
Gender			2.010	0.156
Male	10	7
Female	9	4
Age (years)	51.74 ± 6.11	53.64 ± 5.66	0.842	0.407
Body mass index (kg/m2)	21.49 ± 2.33	24.24 ± 2.11	0.297	0.769
Disease course (years)	0.94 ± 0.33	1.06 ± 0.45	0.849	0.403
Stage			9.853	0.002
I-II	6	10
III-IV	13	1
Education level			7.751	0.005
High school and below	15	3
Bachelor degree or above	4	8
History of smoking	6	5	0.578	0.447
History of drinking	7	5	0.215	0.643
Marital status			0.318	0.853
Married	10	6
Single	4	3
Others	5	2
Payment mode of medical expenses			0.072	0.789
Medical insurance payouts	13	7
Out-of-pocket payment	6	4
Monthly household income (yuan)			15.051	< 0.001
< 5000	13	4
≥ 5000	6	7

Multivariate analysis of influencing factors of patients’ NEs

Multiple logistic regression analysis was performed with NEs (0 = without, 1 = with) as the dependent variable and the statistically different indicators in Table 4 as the independent variables. The results revealed that stage III-IV was a risk factor for NEs (P < 0.05) (Table 5).

Table 5 Logistic regression analysis of influencing factors of patients' negative emotions.

Variables	β	SE	Wald	P value	HR	95%CI
Stage (0 = I-II, 1 = III-IV)	2.447	1.228	3.971	0.046	11.551	1.041-128.172
Education level (0 = high school and below, 1 = undergraduate and above)	-1.499	1.010	2.202	0.138	0.223	0.031-1.617
Monthly household income (0 = < 5000, 1 = ≥ 5000)	-0.882	0.998	0.781	0.377	0.414	0.059-2.927
Constant	0.844	0.950	0.790	0.374	2.327	-

DISCUSSION

Lymphoma was the earliest discovered hematologic malignancy, originating from lymph nodes or extranodal lymphoid tissues or organs, with highly heterogeneous clinical manifestations and prognosis, and is a malignant tumor that seriously threatens human health and life[25]. NHL is one of the major types of lymphoma prevalent in China[26]. The etiology and pathogenesis of NHL are not yet clear and may be related to a family history of cancer, specific viral infections, bacterial infections, and radiation factors[27-29]. Furthermore, it has been suggested that nasal NK/T-cell lymphoma occurs because of the presence of dual-potential early precursor cells that differentiate into immature NK and T-cells or possibly true NK cell tumors[30]. Suffering from cancer is a negative stressful life event, and patients with cancer often adopt various coping strategies. Coping mechanisms and various stress factors often influence and constrain each other, and coping may be influenced by gender, age, culture, occupation, and physical fitness, as well as life events, cognitive evaluation, and social support[31,32]. Because of a lack of understanding of the disease, fear of prognosis, and worry about the possible financial burden, there are significant psychological changes when the patient learns the news of the cancer diagnosis, causing negative psychological experiences such as sadness, depression, and loneliness. Therefore, patients with cancer generally suffer from emotional disorders such as anxiety and depression.

Anxiety and depression are prevalent in patients with cancer. Studies have found that patients with cancer who have developed anxiety and depression can cause self-injury, self-harm, and even commit suicide, which is an important risk factor for the decline of treatment compliance. The results of this study suggest higher SDS and SAS scores in patients with NHL than in healthy controls. Moreover, patients with stage III and IV were observed to have higher SDS and SAS scores than patients with stage I. Among the 30 patients, there were 13 cases (43.3%) of depression, 16 cases (53.3%) of anxiety, and 10 cases (33.3%) of combined anxiety and depression, indicating the presence of NEs in patients with NHL. Patients with cancer often exhibit multiple and complex psychological manifestations simultaneously, such as increased dependence, anxiety, worry, and fear. Once the cancer is diagnosed, it may greatly impact their psychological status, resulting in emotional changes. In addition, being affected by tumor compression can trigger a series of physical symptoms, such as limb swelling, asthma, and pain, thus making patients more prone to NEs. In this study, univariate analysis revealed that the NEs group had a higher proportion of patients with stage III-IV disease, education level at high school or below, and a monthly household income < 5000 yuan than the non-NE group. Furthermore, stage III-IV disease was indicated by the multiple logistic regression analysis to be a risk factor for NEs in patients with NHL. Although multivariate analysis did not identify economic factors as a risk factor, other research has provided inconsistent conclusions, possibly because of the small sample size of this study. Numerous studies have found that financial concerns are associated with anxiety, depression, and worse quality of life in patients with cancer[33]. A higher illness stage is a risk factor for patients to develop NEs. Patients with higher staging experience more severe physical discomfort and complications due to the severity of the illness, which can lead to an exacerbation of the painful experience. In addition, such patients have poor physical strength, increased fatigue, and poor disease tolerance, which can easily affect their emotional status. Moreover, because of the extensive spread of the disease in patients with advanced staging, the therapeutic effect is limited[34], which results in a poorer prognosis, lower self-expectations, and a higher tendency to experience NEs.

This study has some shortcomings. This study included a retrospective design, single-center source, a small sample size, and no follow-up tracking of the patients’ mood changes and other quality-of-life-related elements, which possibly makes the results of this study biased. Moreover, there may be other factors that might influence the mental status of the patients that we did not include, such as treatment methods, gene mutation status, etc. This makes the results less comprehensive. Therefore, a well-designed, multi-center, larger sample size, prospective study is required to further demonstrate the conclusion of the current study and explore additional influencing factors.

CONCLUSION

In summary, patients with higher disease stages of NHL are more prone to experiencing NEs, which should be taken seriously in clinical practice. Moreover, higher disease staging is a risk factor for patients to develop NEs. In clinical practice, medical personnel in the process of daily medical activities should closely observe the changes and progress of each patient's psychological state. This is to ensure the timely assessment of the different psychological characteristics of patients and differing personalities to identify the various ways to stabilize the patient's mood and give spiritual support if needed. Furthermore, timely psychological intervention, psychotherapy, or antipsychotic drugs should be provided to reduce the pressure on the patient and alleviate their anxiety and depression. This may help patients to reduce or relieve their stress, anxiety, depression, and other adverse emotions and cope with the disease so that they can actively cooperate with medical personnel and complete the treatment course.