Abstract

Introduction
Desmoid-type fibromatosis (DTF), also called aggressive fibromatosis, is a rare, benign, locally aggressive condition. Mammary DTF originates from fibroblasts and myofibroblasts within the breast tissue, representing 0.2% of all breast tumors. This study aims to present and discuss the clinical presentation and management of seven cases of breast DTF.

Methods

This single-center case series was conducted at the breast clinic of Smart Health Tower in Sulaymaniyah, Iraq. It included all patients diagnosed as breast DTF by histopathological examination, with those lacking complete data excluded. The patients were treated and managed between January 2021 and August 2024.

Results

This study involved seven female patients with a mean age of 35.29 ± 14.29 years. Clinically, six of them (85.71%) presented with a non-tender palpable breast mass, while one patient (14.28%) reported breast pain. Ultrasound revealed hypoechoic lesions in all cases. The average size of the masses was 29.43 ± 17.26 mm. All patients underwent wide local excision of the breast mass. Histopathological examination confirmed the diagnosis of DTF in all cases.

Conclusion

Diagnosing a desmoid tumor of the breast can be difficult, as it can mimic breast carcinoma. The Wide local excision is often the preferred treatment to prevent future recurrences.

Introduction

Desmoid-type fibromatosis (DTF), also known as aggressive fibromatosis, is a rare benign condition that can develop in various body parts, the most common being the extremities, abdominal wall, and intra-abdominal cavity [1]. Mammary DTF arises from fibroblasts and myofibroblasts within the breast tissue. It accounts for 0.2% of all breast tumors [1,2]. Although it does not metastasize, it is known for its local aggressiveness and high recurrence rate [2].

The term "desmoid" was introduced by Mueller in 1838, deriving from the Greek word "desmos," which refers to its tendon-like consistency. However, MacFarlane first described the disease in 1832 [3].

The DTF may occur sporadically or develop following surgical trauma, the implantation of silicone breast implants, or in association with Gardner's syndrome. While most cases of breast fibromatosis are reported in females, it can also occur in males [1]. It commonly affects individuals between 15 and 60 years of age, with the highest incidence occurring in the third and fourth decades of life [4].

Unpredictable and invasive growth patterns characterize the DTF. The tumor often proliferates during the early stages and may also accelerate due to pregnancy or hormonal changes. After this initial growth phase, many patients experience an extended period where the tumor remains stable [5].

Due to their rarity, desmoid tumors present a diagnostic and therapeutic challenge, as they often initially resemble breast carcinoma and have a high tendency for recurrence [6]. This study aims to describe and discuss the presentation and management of seven cases of breast DTF. All the references cited in this study were evaluated for eligibility [7].

Methods

Study design and setting

This single-center case series was conducted at the breast clinic of Smart Health Tower (Sulaymaniyah, Iraq). The patients were treated and managed between January 2021 and August 2024.

Participants

The study included all patients with confirmed breast DTF based on histopathological examination, while those with incomplete data were excluded.

Data collection

Data were collected from the hospital’s registry, including demographic details, clinical presentation, physical examination, medical history, breast ultrasound and mammography findings, core needle biopsy (CNB) and fine needle aspiration cytology (FNAC) results, histopathological examination (HPE), tumor size, magnetic resonance imaging (MRI) and computed tomography (CT) scan findings, types of surgeries performed, postoperative complications, follow-up duration, and recurrence.

Intervention

All patients underwent surgery under general anesthesia with the supine position following skin preparation and disinfection. The procedures involved making elliptical, radial, and semicircular incisions over the breast where the mass was suspected. After the skin was incised, a wide local excision (WLE) of the mass was performed. In one case, the mass extended into the chest wall muscles and involved two ribs, which were also excised. The long thoracic and thoracodorsal nerves were preserved in all cases. Lymph nodes from levels I, II, and III were removed. Hemostasis was achieved, a Redivac drain was inserted for each patient, and a chest tube drain was placed for one patient. The surgical site was then closed in layers.

Histopathological examination and preparation

Regarding pathologic examination, the specimens were fixed in 10% neutral buffered formalin for 24 hours prior to grossing. After that, the specimens were examined systemically, with appropriate sections taken from the tumors and the margins. The resultant blocks were then processed with the Sakura Histo-Tek VP1 automated processor using a standard 11-hour processing protocol through alcohol, xylene, and paraffin. Following embedding in paraffin and trimming, the blocks were sectioned onto regular glass slides, kept in an oven overnight, and then stained manually for hematoxylin and eosin (H&E) using Gill II hematoxylin. The slides were then dried, and coverslips were applied.

For immunohistochemistry, the paraffin blocks were sectioned onto charged glass slides and kept in an oven overnight. Antigen retrieval was achieved through boiling using the Dako PT Link with a solution of pH 6 or 9, depending on the target antibody. The slides were then washed with buffer solution and welled using the Dako Pen, followed by blocking endogenous peroxidase using hydrogen peroxide. The primary antibodies were then applied, followed by the secondary antibody (horseradish peroxidase) and the chromogen (diaminobenzidine). Counterstaining was achieved using hematoxylin Gill II, followed by drying and applying coverslips.

Data analysis

The data were collected using an Excel spreadsheet (Microsoft Excel 2021). They were analyzed qualitatively with Statistical Package for the Social Sciences (SPSS) software (version 27.0) and presented as mean, range, frequencies, and percentages.

Results

This study included seven female patients with an average age of 35.29 ± 14.29 years, ranging from 18 to 61 years. All of the patients were unemployed, and five of them were married (71.43%). Five patients' medical histories were unremarkable (71.43%), while two patients (28.57%) had hypothyroidism. Three patients (42.86%) had previously undergone different types of breast surgeries. None of the patients had a family history of breast cancer.

Among the clinical presentations, six patients (85.71%) had a non-tender palpable breast mass, while one patient (14.28%) experienced breast pain. Ultrasound showed hypoechoic lesions in all patients with BI-RADS 4 or 5 in four patients (57.14%). The average mass size was 29.43 ± 17.26 mm, ranging from 15 mm to 70 mm. In three cases (28.57%), MRI was used, revealing either heterogeneous or homogeneous masses. In one case (14.28%), a CT scan detected a mass in the chest wall with muscle invasion. A CNB was performed in 5 patients (71.43%), and FNAC of the axillary lymph node, which indicated benign lymphoid tissue, was performed in one patient (14.28%).

Mammography was performed in only one case (14.28%), showing scattered fibro-glandular density and benign calcification. All patients underwent WLE of the breast mass. In one case (14.28%), surgery required rib excision due to chest wall invasion in a recurrent desmoid tumor. The HPE in all cases, along with immunohistochemistry in 5 cases, confirmed the diagnosis of DTF, with no evidence of lymph node metastasis (Fig. 1). The mean follow-up period was 1.51 ± 0.98 years, ranging from 0.7 to 3 years, with no reported recurrences (Table 1).

Discussion

DTF is an intermediate soft tissue tumor marked by clonal fibroblastic proliferation originating in the deep soft tissues. This tumor tends to infiltrate surrounding tissues and has a high local recurrence rate but cannot metastasize [8,9]. They can originate primarily from breast tissue or secondarily from the pectoralis major muscle [1]. This condition typically impacts individuals aged 15 to 60 years, with the highest prevalence observed in the third and fourth decades of life [4]. It is approximately twice as common in women as in men [10]. In this study, the average age of the patients was 35.29 ± 14.29 years, ranging from 18 to 61 years, and all were female.

The exact cause of DTF remains unclear. However, associations with Gardner syndrome, prior trauma, and surgery have been documented [6]. Additionally, while silicone implants are mentioned in the literature as a potential cause, intraoperative trauma is considered more likely to be the primary factor [6].

Clinically, DTF of the breast presents with a wide range of manifestations. It is commonly described as a suspicious, mobile, firm, and painless nodule. However, cases of skin retraction and nipple retraction have also been reported in the literature [6]. Lorenzen et al. described 14 cases of breast DTF in their case series, with all patients presenting with a palpable breast mass [6]. Similarly, in the current study, 85.71% of the patients exhibited a painless breast mass, while only one patient reported breast pain instead of a breast mass.

Relying solely on imaging for diagnosing breast DTF is often inadequate due to its invasive characteristics, which can frequently lead to misdiagnosis as BI-RADS 4 or 5 [10]. On ultrasound, desmoid tumors typically appear as hypoechogenic, ill-defined masses [1]. Mammographically, they present as spiculated masses and, in rare cases, may show calcified deposits [1]. MRI is the most effective imaging technique for assessing the extent of the tumor, particularly when the chest wall is involved [11]. On MRI, desmoid tumors may appear as ill-defined hypointense or isointense masses on T1-weighted images and hyperintense masses on T2-weighted images [12]. In the present study, ultrasound showed hypoechoic lesions in each patient, and ultrasound showed BI-RADS 4 or 5 in 57.14%. Mammography was performed for one patient, showing scattered fibro-glandular density with benign calcifications. MRI was done for three patients, revealing either homogeneous or heterogeneous enhancing masses and varying sizes of fibro-glandular tissue. Additionally, CT scans of one case showed a chest wall mass with invasion of the pectoralis muscle.

Diagnosing a desmoid tumor of the breast can be challenging both clinically and radiologically, as it may resemble breast carcinoma [1]. A definitive diagnosis is only possible through HPE of the lesion. The tumor appears macroscopically as a grayish-white, firm, irregular nodular mass [1]. Microscopically, it is characterized by spindle cells with varying amounts of collagen fiber deposition [12]. Histopathologically, desmoid tumors must be distinguished from scar tissue, fibrosarcoma, or fibromatosis-like metaplastic spindle cell tumors [12].

Immunohistochemical analysis, particularly of preoperative biopsies, can aid in diagnosing desmoid fibromatosis. β-Catenin is a key immunohistochemical marker, showing nuclear expression in sporadic and familial cases in up to 80% of patients [6]. Mutations in the β-catenin gene (CTNNB1) are found in most cases of sporadic DTF, leading to the accumulation of this oncoprotein in the nucleus [6]. Elevated β-catenin levels activate the WnT signaling pathway, contributing to tumor development [6]. However, nuclear β-catenin staining is not specific to breast desmoid fibromatosis; it is also occasionally observed in spindle cell carcinomas, 23% of metaplastic breast carcinomas, and up to 93% of benign phyllodes tumors [13].

The treatment of breast desmoid tumors remains controversial due to the limited data available, given the low incidence of the disease [14]. Various approaches may be employed, including surgery, radiotherapy, chemotherapy, and hormonal therapy. Radical surgical excision is generally considered the treatment of choice [1]. However, complete excision may be avoided in carefully selected patients, especially when the surgery could result in poor functional or cosmetic outcomes, such as in cases where the lesion is superficial or subareolar and may require the removal of the nipple-areolar complex [14]. For some women, mastectomy may be recommended if they experience multiple recurrences, have a large tumor, or face difficulties in obtaining a histological diagnosis [15]. This study chose a comprehensive WLE as a preventive measure to avoid any potential future recurrences.

Breast DTF recurrence is common, with a prevalence of 18-29% over 3-6 years. There is also a risk of involvement with thoracic muscles and ribs [15]. WLE can help prevent or reduce the risk of recurrence [1]. For tumors that are unresectable or require extensive surgical procedures, such as major chest wall resection, radiotherapy may be considered as an alternative treatment option [16]. In this study, no recurrences were observed during the follow-up period. The mean follow-up duration was 1.51 ± 0.98 years, ranging from 0.7 to 3 years.

Systemic therapy can be employed for unresectable or recurrent desmoid tumors, as well as for patients who cannot tolerate surgical treatment or when the tumor involves the chest wall [1]. This therapy includes non-cytotoxic approaches, such as hormonal therapy with Tamoxifen alone or in combination with nonsteroidal anti-inflammatory drugs, as well as cytotoxic approaches like chemotherapy [1]. In the current study, one patient underwent a WLE and the removal of two ribs due to an irregular mass on the right chest wall that invaded the pectoralis muscle and contacted the intercostal muscle. A limitation of this study is the short follow-up duration, which may not be long enough to identify potential recurrences.

Conclusion

Diagnosing a desmoid tumor of the breast can be difficult, as it can mimic breast carcinoma. The WLE is often the preferred treatment to prevent future recurrences.

Declarations

Conflicts of interest: The author(s) have no conflicts of interest to disclose.

Ethical approval: The study's ethical approval was obtained from the scientific committee of the Kscien Organization for Scientific Research.

Patient consent (participation and publication): Verbal informed consent was obtained from patients for publication.

Source of Funding: Smart Health Tower

Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.

Acknowledgements: None to be declared.

Authors' contributions: AMS and AMA were major contributors to the conception of the study, as well as to the literature search for related studies. HAN, MKA and AAQ were involved in the literature review, study design, and writing the manuscript. ZDH, HAY, SHH, SOK, FHK and HAS were involved in the literature review, the design of the study, the critical revision of the manuscript and the processing of the figures. FHK and AMS confirm the authenticity of all the raw data. RMA was the pathologist who performed the histopathological diagnosis. LRAP was the radiologist who performed the assessment of the case.  All authors have read and approved the final manuscript.

Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data.

Data availability statement: Note applicable.

Abstract

Introduction

Failure of an arteriovenous fistula (AVF) disrupts hemodialysis access and reduces the available area for future access. Preventive interventions are necessary to avoid AVF failure. This study evaluates the impact of surgical drainage during AVF creation for hemodialysis in patients with end-stage renal disease (ESRD).

 Methods

This single-center, phase II, randomized controlled trial was conducted from June 2020 to June 2023. Ninety-four patients were randomly assigned into two groups: Group A (with a surgical drain) and Group B (without a drain). Patients were followed for six months post-surgery. The primary outcome was AVF primary patency, and secondary outcomes included postoperative complications.

Results

The average age of participants was 63.7 years, with 50 male patients. The most common cause of renal failure was glomerular disease (29.8%), and most AVFs were located on the left side (57.4%). Brachiocephalic AVFs were the most frequent type (70.2%). Postoperative hematoma was more common in Group B (42.6%) than in Group A (17%) (P = 0.007). The primary patency rate at six months was higher in Group A (87.2%) compared to Group B (76.6%), though the difference was not statistically significant (P = 0.180).

Conclusion

The use of surgical drainage during AVF creation may reduce postoperative complications, such as hematomas, and potentially improve primary patency rates, contributing to better outcomes for patients undergoing hemodialysis.

Introduction

Renal failure is a serious public health problem, and its incidence is increasing. Nowadays, hemodialysis (HD) and kidney transplantation are the main therapies for end-stage renal disease (ESRD) [1]. Regardless of the rise in kidney transplant surgeries, HD remains the mainstay of treatment. In the majority of cases, a phase of hemodialysis preceded the transplantation [2]. Patients who depend on HD require proper vascular access. According to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) recommendations, optimal vascular access should offer an appropriate flow rate, durability, and a low risk of complications [3].
There are three main types of chronic vascular access for HD, including native arteriovenous fistula (AVF), arteriovenous shunts employing graft material (AV graft), and central venous catheter (CVC). Among them, AVF stands out as the primary vascular access worldwide, given its superior long-term primary patency rate, minimal need for secondary procedures, and its association with longer survival rates and lower complication rates [4,5]. The NKF-DOQI recommended the radiocephalic fistula in the nondominant forearm as the primary choice for access [6]. With the growing emphasis on AVF and the evolving dialysis population, which now includes a higher proportion of older patients with cardiovascular comorbidities, upper arm fistulas have gained popularity in recent years [7]. The cephalic vein is superficial in the forearm and is easily injured by previous venipunctures, making the creation of radiocephalic AVF difficult. Hence, with the ability to protect the cephalic vein in the arm, a brachiocephalic AVF becomes a practical alternative procedure. [8]. Currently, brachiocephalic AVF is increasing in popularity because of the higher failure rate of radiocephalic fistulas [9]. Insufficient vascular access and associated consequences have been identified as the cause of mortality in about 25% of all patients initiating HD. [5]. Failure of an AVF not only disrupts functional access but also reduces the available area from which another access may be established. Furthermore, interventional techniques must be performed on the patients to repair the failure of AVFs. As a result, minimizing post-operative complications that impact AVF patency and failure rates is of critical importance [9].

The current study aims to assess the overall outcomes and effects of surgical drainage in AVFs for hemodialysis patients with renal failure.

Methods

Study design and setting

This was a single-center, phase II, open-label, parallel-arm, randomized controlled trial (RCT) conducted between June 1, 2020, and June 1, 2023, involving ESRD patients in need of AVF for hemodialysis or maintenance hemodialysis. The trial aimed to investigate the outcomes and complication rates of AVFs with and without postoperative surgical drains in patients undergoing AVF creation. The study was conducted in accordance with the Helsinki Declaration. The study proposal was approved by the scientific and ethical committee of B.P. Koirala Institute of Health Sciences. All patients consented to participate in the trial and the publication of their information. The study's details have been registered in the Chinese Clinical Trial.

Participants

All patients who underwent native AVF creation were included in this study. Participants were excluded if they matched any of the following criteria: (1) having a bleeding disorder; (2) history of antiplatelet use; (3) previous AVF creation; (4) cephalic vein diameter less than 3 mm.

Randomization and masking 

Once eligibility was established, the patient's electronic file was initially admitted to a designated mailbox in hospital's database. The second registration was completed after confirming all preoperative requirements for inclusion by computerized assignment. The participants were assigned randomly (1:1) into two groups, Group A (inserting a surgical drain at the site of the AVF) or Group B (without a surgical drain). The final registration was done when the patient was discharged home, followed up regularly, and met all the inclusion criteria. No masking of the operators or participants in the allocation was performed.

Preoperative assessment

All patients underwent clinical examination to assess the adequacy of the venous and arterial systems of the upper limbs. If the vein was not visible, duplex scanning was requested. Basic investigations, including a complete blood count, viral markers, and electrolytes, were done for all of the cases. Preoperative antibiotic (Cefepime 1gm iv) was given to all of the patients.

Procedure

In the supine position, under local anesthesia (15 cc lidocaine 2%) using a transverse antecubital incision, an end-to-side AVF was created.  One cc of heparin (5000 IU) was injected before arterial clamping, and no reversal agent was used in the completion of the procedure. Six zero Prolene with an 8 mm needle was used as the suture material in all procedures.  A Redivac drain (size 18 in brachiocephalic and size 16 in radiocephalic AVF) was inserted in the subcutaneous tissues inferolateral to the incision.  The patient remained in the hospital overnight. Postoperatively, they were given oral analgesics and antibiotics for five days in accordance with the hospital infection prevention protocol.

Outcome

Postoperatively, patients were followed up regularly for six months. The primary outcome was the primary patency of the AVF, while the secondary outcomes included postoperative complications such as hematoma, pain, reopening, and wound infection.

Statistical analysis

The database of the hospital was used to collect patient data. The collected data were analyzed using the Statistical Package for the Social Sciences 25.0 software. The qualitative data were presented in the form of frequency and percentages, and the Chi-square (X2) test was used to compare them. A P-value of less than 0.05 is considered significant.

Results

During the follow-up period, 94 patients were registered for the trial. The mean age of the patients was 63.7 years ranging from 44 to 81 years. Fifty cases (53.2%) were male and 44 (46.8%) were female. The most common cause of renal failure was glomerular disease (29.8%), followed by diabetic nephropathy (22.3%), and analgesic nephropathy (11.7%). Fifty-four (57.4%) patients had a history of temporary vascular access (CV line) (Table 1). The majority of the AVFs were located on the left side (57.4%). Brachiocephalic was the most common type of AVF (70.2%) followed by radiocephalic fistula (18.1%) (Table 2). Postoperative hematoma was more common in Group B (42.6%) than in Group A (17%) and reached a significant level (P-value = 0.007). About 10.6% of cases in Group B underwent reopening of the fistula while none of the cases of Group A underwent reopening. Although the difference wasn’t statistically significant, the primary patency rate at six months was relatively higher in Group A (87.2%) than in Group B (76.6%) (P-value 0.180) (Table 3). One patient developed an infection which was in the experimental group. In the experimental group, individuals experiencing primary failure were somewhat older, with ages ranging from 55 to 74 years, compared to the total participants. Five of the six cases of primary failure in the experimental group were female (83.3%).

Discussion

Around the world, there is a continuous increase in the number of ESRD patients admitted for renal replacement therapy. Because HD is the recommended treatment for the great majority of these patients, permanent vascular access is the only means to survive. As a result, the effective creation of permanent functional vascular access is essential for providing adequate HD therapy in ESRD [10]. A well-functioning AVF is ideal vascular access for HD and has a major influence on patient outcome and survival [11]. Patients’ survival and quality of life are also impacted by vascular access complications. Therefore, the appropriate management to decrease the complications is mandatory [12]. However, as the life expectancy of patients undergoing HD has increased over time, many of them will require additional vascular access operations throughout their lives [6]. The distal radiocephalic AVF is the preferred vascular access, followed by other alternative accesses. However, multiple factors, including obesity, unavailability, exhaustion, and calcified vessels make alternative vascular access mandatory [13]. The primary issue with AVF has always been the high risk for early thrombosis, which results in early failure [1]. Other common consequences influencing AVF patency include stenosis, thrombosis, bleeding, infection, and flow problems [13].

Ates et al. discovered that the brachiocephalic group had higher complications than the radiocephalic group. However, for hematoma, the situation was reversed, as it occurred in 5.9% of the brachiocephalic group and 6.9% of the radiocephalic group without a significant effect [2]. Thabet et al. reported hematoma in 20 (8.4%) of their patients. Seventeen (85%) patients were effectively treated with hematoma evacuation and repair of the puncture site. Because of late presentation with possibly contaminated hematomas, the remaining three (15%) patients had their access ligated [14]. The bleeding rate in the studies by Magar et al., Elamurugan et al., and Madhhachi et al. were 9.75%, 11.5%, and 5.3% respectively [5,6,10]. In the current study, hematoma was more common in the experimental group than in the control group, and the result was statistically significant (P-value = 0.007).

A significant problem with AVFs is the high rate of primary failure, which can be caused by a lack of maturation or early thrombosis [15]. A comprehensive strategy is essential in detecting and addressing the principal causes of primary failure in individuals with ESRD. Despite current research outlining the pathophysiology of the technique and biomechanical challenges connected with maturation, the process of AVF maturation remains complicated and poorly understood. Intimal hyperplasia has been identified as the most severe pathohistological alteration that occurs in blood vessels and has been linked to AVF primary failure [9]. In a study that compared the primary patency of radiocephalic AVF and brachiocephalic AVF, brachiocephalic AVF had the highest patency rate (79.18%), followed by mid-arm radiocephalic AVF (72%), and distal arm radiocephalic AVF (68.18%) [5]. In a meta-analysis of 46 reports, the probability of primary failure was 23%, but it raised to 37% in old-aged patients [16,17]. According to Zouaghi et al., the actual primary patency rates at six months, 1 year, 2years, 4years, and 5years were 82%, 78%, 69%, 61%, and 42%, respectively [18]. Wong et al. reported that primary patency at three months and one year for brachiocephalic fistula was 87.9% and 63.1%, respectively, and 84.6% and 58.1% for radiocephalic fistula [19]. Mahalkar et al. reported brachiocephalic AVF patency of 88%, 83%, and 71% at 30 days, 90 days, and six months, respectively [20]. The current study's primary patency rate at six months was 87.2% for the control group, which was slightly higher than the control group's rate of 76.6%.

Age, gender, race, diabetes, peripheral vascular disease, history of coronary artery disease, location of the fistula, and obesity are all patient factors that predict primary failure [17]. However, some studies reported that age did not affect primary patency [14,21]. Smith et al.’s review of the literature revealed an increase in access failure in the elderly population [22]. There is limited evidence that AVF patency varies by gender. Several studies discovered that when the patency rate was examined by gender, male patients had a much greater rate than female patients [23].  This finding is explained by the fact that females have a smaller diameter of arteries and so have a lower AVF patency rate than males [22]. However, Mortaz et al. found no evidence that AVF survival was gender-dependent [24]. In the experimental group of the current study, those with primary failure were somewhat older (ages ranging from 55 to 74 years) than the total participants. Five of the six cases of primary failure in control group were female, which might indicate that females are more prone to failure than males.

Infection is responsible for 20% of all AVF consequences. The majority of AVF infections involve perivascular cellulitis, which often appears as localized erythema and edema and is easily treated. An infection linked to anatomical abnormalities such as aneurysms, hematomas, or abscesses is far more dangerous and necessitates surgical excision and drainage [25]. The infection rates in studies by Dekhaiya et al. and Schinstock et al. were 8% and 26.8%, respectively [26,27]. In a study by Shameri et al., infection was observed in 17 (7.4%) of the cases, with the majority of the cases (10, 4.4%) being managed with observation (antibiotic) or aspiration and draining. Other seven (3%) infections progressed to ruptured fistulae, which required emergent surgical treatment [9]. Another study reported that 57 (23.8%) patients had severe infections in the form of abscess formation or active bleeding. As a result, conservative therapy was out of the option, and they all had immediate access closure [14]. Only one patient developed an infection in the current study, which was in the experimental group. The patient was treated conservatively with antibiotics for five days and responded well to the treatment.

One of the present study's limitations was the sample size which was small and only covered participants from a single center. However, because this is a hypothesis-generating study, more study on this concept is needed.

Conclusion

The use of surgical drainage after AVF surgery might be beneficiary.  It may decrease the complications associated with AVF creation and improve the fistula's primary patency.

Declarations

Conflicts of interest: The author(s) have no conflicts of interest to disclose.

Ethical approval: The study was approved by the B.P. Koirala Institute of Health Sciences Ethical Committee (No.11).

Patient consent (participation and publication): Written informed consent was obtained from patients for publication.

Source of Funding: B.P. Koirala Institute of Health Sciences.

Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.

Acknowledgements: None to be declared.

Authors' contributions: LSJ was significant contributor to the conception of the study and the literature search for related studies.  NO and SV were involved in the literature review, the study's design, the critical revision of the manuscript, they participated in data collection, involved in the literature review, study design, and manuscript writing. SV and LSJ confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.

Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data.

Data availability statement: Not applicable.

Abstract

Introduction

Given pregnancy's significant impact on hematological parameters, monitoring these changes across trimesters is crucial. This study aims to evaluate hematological profiles in pregnant women, primarily focusing on the prevalence of anemia and thrombocytopenia throughout the different trimesters.

 Methods

This retrospective cross-sectional study was conducted at Smart Health Tower from March to December 2024, with ethical approval from Kscien Organization. Pregnant women aged 18-45 years in any trimester were included, excluding those with pre-existing hematological disorders or significant complications. Blood samples were collected during routine antenatal visits for hematological analysis. Data were analyzed using IBM SPSS version 26.0, with statistical significance set at p<0.05.

Results

This study included 243 pregnant women, with a mean age of 29.91 ± 6.32 years. The average hematological parameters were as follows: white blood cell count 9.45 ± 2.10 × 10⁹/L, red blood cell count 4.21 ± 0.45 × 10¹²/L, hemoglobin 11.93 ± 1.03 g/dL, and platelet count 239.11 ± 59.47 × 10⁹/L. Anemia and thrombocytopenia were identified in 16.0% and 5.0% of participants, respectively, with significant trimester-related variations (p= 0.033, p= 0.006). The highest prevalence of anemia (30.8%) was observed in women aged 26–30 years.

Conclusion

Significant changes in hematological parameters across pregnancy trimesters highlight the need for regular monitoring to diagnose and manage anemia, thrombocytopenia, and other abnormalities, ensuring optimal maternal and fetal health.

Introduction

Alterations in hematological profiles are critical factors influencing pregnancy and its outcomes. These changes occur to support the growing fetus and placenta, resulting in significant modifications in blood volume. Consequently, hematological profiles are commonly assessed as a reliable, cost-effective means of evaluating overall health during pregnancy [1]. One of the key changes during pregnancy is an increase in plasma volume by an average of 40 to 45%. This rise is triggered by the direct effects of progesterone and estrogen on the kidneys, which stimulate the release of renin and activate the renin-angiotensin-aldosterone system [2]. Additionally, pregnancy-induced physiological stress leads to an elevation in the peripheral white blood cell (WBC) count, especially neutrophils. However, platelet levels tend to decrease due to hemodilution and increased platelet activation, particularly in the third trimester [3].

While most hematological changes during pregnancy are physiological, abnormal blood profiles can have significant impacts on both pregnancy outcomes and maternal health. Hematological complications, including anemia and thrombocytopenia, are among the leading causes of maternal mortality [4]. Anemia increases the risks of maternal, fetal, and neonatal mortality, as well as poor pregnancy outcomes and long-term developmental issues for children [5]. Thrombocytopenia affects 8-10% of pregnant women, particularly in the third trimester. Although 75% of cases are mild and benign (gestational thrombocytopenia), it can also signal more severe conditions like preeclampsia or hemolysis, elevated liver enzymes and low platelets syndrome, which pose life-threatening risks for both mother and baby [6].

Anemia in pregnancy, defined by a hemoglobin concentration below 110 g/L, has a global prevalence of 36.5% [7]. The condition is especially prevalent in Africa and Asia, with Ethiopia reporting a notably high prevalence of 62.7%. Severe anemia during pregnancy can lead to complications such as preterm birth, miscarriage, low birth weight, surgical delivery, postpartum hemorrhage, and fetal mortality [2].

Given the significant influence of pregnancy on hematological parameters, it is essential to monitor these changes throughout the pregnancy trimesters [8,2]. This study aims to assess the hematological profiles of pregnant women attending two antenatal care centers in Iraq. Specifically, it will examine the prevalence of anemia, other hematological parameters, and the occurrence of thrombocytopenia across different trimesters, providing valuable insights for early detection of complications and appropriate treatment. The references have been thoroughly reviewed and their eligibility has been confirmed [9].

Methods

Study design and setting

This retrospective cross-sectional study was conducted at Maternity Hospital and Smart Health Tower from February 2023 to December 2024. The study was approved by the ethical board at the Kscien Organization (25/No. 29). Informed consent was obtained from the participants to include their data, and all the data were de-identified to ensure confidentiality.

Participants

The participants were selected based on specific inclusion and exclusion criteria. Pregnant women aged between 18 and 45 years in their first, second, or third trimester and attending Maternity Hospital and Smart Health Tower antenatal clinics were eligible to participate. Women were excluded if they had pre-existing hematological disorders, chronic illnesses such as diabetes or hypertension, or significant pregnancy complications such as pre-eclampsia. Those taking hematological-modifying medications beyond standard prenatal care were also excluded. Recruitment was carried out during routine antenatal visits, where trained research assistants provided detailed information about the study. Written informed consent was obtained from all participants who met the eligibility criteria.

Data Collection

Demographic and clinical information were collected from all participants through a database and structured questionnaire administered by trained personnel. The data included details such as age, trimesters, education level, occupation, and residential status.

Blood Collection and Analysis

Blood samples were collected from participants during their scheduled antenatal visits. To standardize the results, samples were drawn in the morning after an overnight fast. Certified phlebotomists performed venipuncture under aseptic conditions, obtaining approximately 5 mL of blood from each participant into ethylene diamine tetra acetic acid -coated vacutainer tubes. The samples were labeled with unique identifiers and transported to the laboratory within 30 minutes in temperature-controlled containers (2–8°C).

Hematological analyses were performed in the diagnostic laboratory. The parameters assessed included red blood cell (RBC) indices such as RBC count, hemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). The WBC parameters, including total WBC count, granulocyte count, lymphocyte count, and monocyte count, were also measured, along with platelet parameters such as platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width. The analyzer was calibrated daily to ensure the accuracy and precision of the results, and quality control was maintained through the use of internal control samples and participation in external proficiency testing programs. According to the World Health Organization, anemia in pregnancy is diagnosed when Hb concentration falls below 11.0 g/dL. Anemic pregnant women are classified into three categories based on their Hb levels: mild anemia with Hb between 10.0 and 10.9 g/dL, moderate anemia with Hb between 7.0 and 9.9 g/dL, and severe anemia with Hb levels below 7.0 g/dL [10]. In the case of thrombocytopenia, it is identified when the platelet count drops below 150 × 10⁹/L. Thrombocytopenia is further classified as mild when PLT counts range from 100 to 150 × 10⁹/L, moderate when they are between 50 and 100 × 10⁹/L, and severe when PLT levels are below 50 × 10⁹/L [11].

Statistical analysis

The collected data were systematically organized and recorded using Microsoft Excel 2021 for effective management. Statistical analysis was performed with IBM SPSS Statistics version 26.0. The Shapiro-Wilk test was applied to assess the normality of continuous variables. For normally distributed data, means and standard deviations were calculated, and group comparisons were made using independent t-tests. For non-normally distributed data, medians and interquartile ranges were computed, with comparisons conducted using the Mann-Whitney U test. Categorical variables were analyzed using chi-square tests or Fisher’s exact test as appropriate. A p-value of less than 0.05 was considered statistically significant for all analyses.

Results

Participant Demographics

The study included 243 pregnant women, with an average age of (29.91± 6.32) years, ranging from 18 to 47 years. Among them, 181 (74.5%) were housewives. Regarding education, 57 individuals (23.5%) had secondary education, while 84(34.6%) had attended college. In terms of residence, 202 (83.1%) were from urban areas (Table 1).

Hematological Parameters and Their Changes Across Trimesters

The mean values of selected hematological parameters for the study participants were as follows: WBC count, 9.45±2.10 × 10⁹/L; RBC count, 4.21±0.45 × 10¹²/L; Hb, 11.93±1.03 g/dL; hematocrit, 35.75±3.04%; MCV, 85.31±7.04fL; MCH, 30.43±20.59pg; MCHC, 33.46±1.15%; and PLT count, 239.11±59.47× 10⁹/L.  The mean WBC counts for pregnant women were 9.14 ± 1.65, 10.32 ± 2.28, and 8.89 ± 2.05 (× 10^9/L) during the first, second, and third trimesters, respectively. Statistically significant differences were observed between the second and third trimesters (P < 0.001), as well as between the first and second trimesters (P = 0.001). Regarding RBC count, the mean value in the first trimester (4.45 ± 0.36 g/dL) was significantly higher than that in the second trimester (4.03 ± 0.42 g/dL) and third trimester (4.15 ± 0.46 g/dL). Likewise, the mean Hb level in the first trimester (12.36 ± 0.94 g/dL) was significantly higher than in the second trimester (11.70 ± 0.92 g/dL) and third trimester (11.73 ± 1.10 g/dL). Although no significant difference was observed in hematocrit values between the first and third trimesters, a significant difference (P < 0.001) was noted between the first and second trimesters, with higher values in the first trimester (36.77 ± 2.65) compared to the second trimester (34.72 ± 2.86). Furthermore, the mean PLT count was significantly lower in the second (240 ± 58) and third trimesters (211 ± 53) compared to the first trimester (267 ± 54). On the other hand, the mean values for MCHC, platelet distribution width showed no significant differences across the trimesters (Table 2).

Prevalence and Variation of Anemia and Thrombocytopenia Across Trimesters

In the present study, 39(16.0%) of study participants were anemic, while 12(5.0%) were thrombocytopenic.  Thrombocytopenia differed significantly across trimesters (P = 0.006). No thrombocytopenia was observed in 80(34.6%), 79(34.2%), and 72(31.2%) women in the first, second, and third trimesters, respectively, while mild thrombocytopenia increased to 9 (75.0%) in the third trimester from 2(16.7%) in the second and 1(8.3%) in the first trimester. Anemia also varied significantly (P = 0.033), with no anemia present in 74(36.3%), 66(32.3%), and 64(31.4%) women in the first, second, and third trimesters, respectively (Table 3).

3Hematological Parameter Variations by Age, Occupation, and Residence

Significant differences in WBC and granulocytes (both P < 0.001) were observed across age groups, with the highest values recorded in the 21–25 age group for WBC (10.3 ± 2.32) and granulocytes (7.33 ± 1.95). Other parameters, including lymphocytes, RBC, Hb, hematocrit, and PLT indices, showed no significant variation among age groups (P > 0.05). In terms of occupation, no significant differences were found across parameters. For residence, no significant differences were noted in WBC, granulocytes, or other parameters (P > 0.05); however, rural residents exhibited slightly higher platelet counts (253 ± 58) compared to urban residents (237 ± 60) (Table 4).

Socio-Demographic Distribution of Anemia Cases

Regarding the distribution of socio-demographic variables among anemia cases, the 26–30 years age group exhibited the highest prevalence, with 12 cases (30.8%), including 4 cases (57.1%) of moderate anemia. In terms of occupation, housewives were the most affected, accounting for 28 cases (71.8%) of anemia, primarily mild 22(68.8%) and moderate 6(85.7%) (Table 5).

Discussion

Regular monitoring of hematological profiles is essential for identifying and managing health conditions in pregnant women. Among these, anemia is the most prevalent hematological disorder during pregnancy, followed by thrombocytopenia. The prevalence of anemia varies across regions, with rates of 45.8% in Africa, 47.8% in South-East Asia, and 23.5% in Europe [7]. This study reports a significantly lower anemia prevalence of 16.0% compared to findings from other regions. For instance, higher anemia rates have been documented in countries such as Ethiopia 16.6%, Nigeria 39.8%, and Mexico 27.8% [12-14]. A study conducted at Debre Berhan Referral Hospital in Ethiopia, which included 284 pregnant women, reported an anemia prevalence of 2.8% [15], lower than that observed in the present study. Such variations may be explained by differences in socioeconomic and educational status, dietary patterns, contributing factors to anemia, and unequal access to healthcare services and iron supplementation. Moreover, pregnant women’s awareness of antenatal care follow-ups and the methods used to measure hemoglobin levels could influence results, as some studies employed less precise techniques compared to the automated hematology analyzers used in this study.

Severe anemia during pregnancy can lead to serious complications, including impaired fetal growth and development, maternal fatigue, and an increased likelihood of cesarean delivery. This highlights the need for early diagnosis and proper management to improve outcomes for both the mother and the child. In a large cohort study involving over 18 million pregnant women, severe anemia was diagnosed in only 0.21% of cases, while the overall prevalence of anemia was reported at 17.78% [16]. Similarly, a study in Tanzania found that 7.2% of pregnant women had severe anemia, contributing to an overall anemia prevalence of 83.5% [17]. Another study, which included 515,270 women, revealed that severe anemia was present in just 0.02% of cases, with mild and moderate forms of anemia being more common at 11.8% and 0.43%, respectively [18]. In contrast, the current study reports a 0% prevalence of severe anemia, suggesting that effective preventive measures or nutritional interventions may be in place. This significant difference warrants further investigation into the factors contributing to these results.

The age distribution of pregnant women affected by anemia has been extensively studied, revealing varying trends across different populations. In a study conducted in Somaliland, in which 360 pregnant women enrolled, it was found that 46.7% of the participants were aged between 21 and 29 years, and this group exhibited a higher prevalence of anemia compared to younger women aged 20 years or younger, who had a prevalence of only 13.7% [19]. Similarly, according to a study in which a dataset of 21 Sub-Saharan African countries were collected between 2015 and 2022, indicated that women aged 20-24 years were at a higher risk for anemia, while those in older age (25-29 years) showed a decreased risk [20]. In contrast, a comprehensive analysis involving over 880,000 women in low- and middle-income countries reported that pregnant women aged 25-34 and 35-49 had a reduced risk of anemia by 12% and 23%, respectively, compared to younger cohorts [21]. The current study, however, found that the 26–30 years age group exhibited the highest prevalence of anemia, at 30.8%. The discrepancy between the findings of these studies and the present study may be attributed to differences in the timing of the studies, variations in lifestyle factors, and disparities in access to healthcare facilities among the participants.

Thrombocytopenia during pregnancy is a notable concern, particularly in the later trimesters, with various studies documenting its prevalence and associated factors. In a study conducted at Gondar University Hospital in Ethiopia, the overall prevalence of thrombocytopenia among pregnant women was 8.8%, predominantly mild cases, with no significant association was observed between the trimester and thrombocytopenia prevalence [22]. A systematic review reported that thrombocytopenia affects approximately 5% to 10% of pregnant women, with a notable increase in cases observed during the third trimester due to physiological changes such as hemodilution [6]. Consistent with these findings, the current study also observed a higher likelihood of thrombocytopenia in the third trimester. This emphasizes the importance of routine platelet count monitoring during antenatal visits, enabling timely diagnosis and facilitating optimal feto-maternal outcomes across all types of thrombocytopenia during pregnancy.

The mean WBC count among pregnant women shows notable variations across different trimesters, as highlighted by several studies. A comprehensive longitudinal study involving 80,637 measurements found that the total WBC count increased significantly during pregnancy, with an upper reference limit elevated by 36% compared to non-pregnant levels, reaching a range of 5.7-15.0 × 10^9/L. This increase was primarily driven by a 55% rise in neutrophils, which remained stable throughout gestation, while lymphocyte counts decreased by approximately 36% [23]. In a study from Jordan, the mean WBC count in the first trimester was reported at 7.52 × 10^9/L, with significant increases observed in subsequent trimesters, reflecting the physiological changes associated with pregnancy [24]. In comparison, the current study found a different trend in WBC count across trimesters. Specifically, the WBC count increased from the first to the second trimester but then decreased from the second to the third trimester. This observed variation may be attributed to study design, life style, or population differences between study groups.

The current study revealed that the RBC count was significantly higher in the first trimester compared to both the second and third trimesters (4.45 ± 0.36 versus 4.03 ± 0.42 and 4.15 ± 0.46, P<0.01), with a similar trend observed for Hb levels. Regarding hematocrit values, although higher in the first trimester, no significant changes were noted between the first and third trimesters. This finding contrasts with studies conducted at Debre Berhan Referral Hospital in North Shoa, Ethiopia, where changes in both Hb and hematocrit values were not statistically significant across the trimesters [15]. In contrast, two studies conducted in Port Harcourt and Nigeria reported a significant decrease in Hct values as gestational age progressed [1,25]. These discrepancies may be attributed to regional variations, and healthcare differences.

The MCV, MCH, and MCHC demonstrate significant variations throughout the trimesters of pregnancy, reflecting the physiological changes that occur during this period. In a longitudinal study involving pregnant women, MCV was observed to decrease in the first trimester, reaching its lowest point before gradually returning to normal levels by the third trimester. Similarly, MCH values fell slightly during the first trimester but increased in the second trimester before declining again in the third trimester. MCHC showed a different trend, initially increasing in the first trimester and then gradually declining throughout the pregnancy [26]. In contrast to these trends, the current study found that MCV increased gradually from the first trimester (82.87 ± 5.53 fL) to the third trimester (86.63 ± 8.27 fL), while MCH values decreased from the first trimester (33.54 ± 35.38 pg) to the third trimester (28.47 ± 3.12 pg), and MCHC showed a slight increase in the second trimester (33.83 ± 1.08%) before decreasing in the third trimester (32.89 ± 1.20%). These differences may reflect variations in iron deficiency prevalence among study populations across countries. Additionally, the increase in MCV with gestational age could be attributed to the lower prevalence of anemia and the adequate supply of micronutrients, such as iron, which supports the maintenance of normal hematologic profiles, in contrast to the plasma volume dilution effect.

This study is limited by its retrospective design, which inherently carries the risk of selection and information biases due to reliance on pre-existing clinical records, potentially leading to incomplete or inaccurate data. Furthermore, the lack of direct assessment of iron and other micronutrient deficiencies represents a significant limitation, as these deficiencies are well-established determinants of hematological parameters in pregnancy.

Conclusion

Significant changes in hematological parameters across different trimesters of pregnancy, emphasizing the importance of regular monitoring throughout this period. Consistent evaluation of these parameters is crucial for the timely diagnosis and management of anemia, thrombocytopenia, and other hematological abnormalities, thereby ensuring optimal maternal and fetal health during antenatal care.

Declarations

Conflicts of interest: The author(s) have no conflicts of interest to disclose.

Ethical approval: The study was approved by the ethical committee of the Kscien organization (No.29).

Patient consent (participation and publication): Written informed consent was obtained from patients for publication.

Source of Funding: Smart Health Tower.

Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.

Acknowledgements: None to be declared.

Authors' contributions: DOK and AMSA were significant contributors to the conception of the study and the literature search for related studies.  AKQ, MNA, SNO, HBJ, MTT, and RAE were involved in the literature review, the study's design, the critical revision of the manuscript, they participated in data collection. AMM, BAA, SHM, and RQS involved in the literature review, study design, and manuscript writing. BAA and RQS confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.

Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data.

Data availability statement: Not applicable.

Abstract

Introduction

Non-Hodgkin lymphoma (NHL) of the thyroid, a rare malignancy linked to autoimmune disorders, is poorly understood in terms of its pathogenesis and treatment outcomes. This study aims to review a single-center experience in managing primary thyroid non-Hodgkin B-cell lymphoma cases.

 Methods

This retrospective case series was conducted at a single center from January 2020 to November 2024, including patients diagnosed with B-cell NHL of the thyroid who underwent surgical intervention. Data, including clinical, demographic, laboratory, and imaging information, were extracted from medical records. Diagnostic procedures involved core needle or surgical biopsy with immunohistochemistry analysis. Treatment included excisional biopsy, thyroidectomy, lobectomy, and chemotherapy. Quantitative data is presented as means and standard deviations, and qualitative data as frequencies and percentages.

Results

Among nine NHL cases, seven (77.8%) were female, with a mean age of 60.78 ± 12.53 years. Anterior neck swelling was the most common presentation in 6(66.7%) cases. Seven patients (77.8%) received R-CHOP chemotherapy; histopathology confirmed B-cell lymphoma in eight cases (88.9%). Thyroid function was euthyroid in four cases (44.4%), hypothyroid in three (33.3%), and hyperthyroid in one (11.1%). TI-RADS (Thyroid Imaging Reporting and Data Systems) classification showed five cases (55.6%) as TI-RADS 5. Follow-up revealed no recurrence in four cases (44.4%), and two deaths (22.2%).

Conclusion

Primary thyroid NHL is a rare condition requiring early diagnosis and personalized treatment. The variability in treatment responses highlights the need for individualized approaches to optimize patient outcomes.

Introduction

Non-Hodgkin lymphomas (NHLs) represent a heterogeneous group of lymphoid malignancies from lymphocytes, predominantly of B-cell origin. While many NHLs develop within lymph nodes, approximately 30-40% originate in extra-nodal sites [1]. Primary thyroid lymphoma is defined as a lymphoma that arises from the thyroid gland, excluding those that invade the thyroid due to either metastasis or direct extension. This rare malignancy accounts for approximately 5% of all thyroid malignancies and only 1-2% of all extra-nodal lymphomas, with an estimated annual incidence of 2 cases per million population [2].

The precise pathogenesis of primary thyroid lymphoma remains unclear. However, associations between autoimmune diseases, chronic antigenic stimulation, and the development of primary thyroid lymphoma have been identified. The most significant risk factor for primary thyroid lymphoma is the presence of hashimoto's thyroiditis, with patients affected having a risk of developing primary thyroid lymphoma that is 40 to 80 times higher. Notably, the incidence of hashimoto's thyroiditis among primary thyroid lymphoma patients is nearly 80% [3,4]. The proposed pathogenesis involves chronic antigenic stimulation from autoimmune processes leading to persistent lymphoid proliferation, eventually undergoing malignant transformation. Recent research has also implicated mutations in regulatory pathways, particularly the NF-κB signaling pathway through A20 gene mutations or deletions, in the development of certain thyroid B-cell lymphomas [5]

Primary thyroid lymphomas are almost exclusively NHL, with B-cell phenotype representing over 95% of cases [6]. Histologically, diffuse large B-cell lymphoma is the most common subtype, accounting for approximately 60-70% of cases. Meanwhile, mucosa-associated lymphoid tissue lymphoma represents the second most common subtype, comprising about 20-30% of cases. Other less common variants include Burkitt lymphoma [7]. These subtypes exhibit varying clinical behaviors and prognoses, necessitating accurate diagnosis for appropriate management.

Despite advances in understanding the pathophysiology and management of primary thyroid lymphoma, several knowledge gaps persist regarding optimal therapeutic strategies and long-term outcomes. This study aims to review a single-center experience in managing primary thyroid non-Hodgkin B-cell lymphoma cases. The eligibility of the references has been verified [8].

Methods

Study design and setting

This retrospective case series study was conducted at Smart Health Tower. It included patients diagnosed with NHL of B-cell origin in the thyroid gland based on pathological diagnosis who underwent surgical intervention, excisional biopsy, or thyroidectomy for definitive diagnosis. The study spanned from January 2020 to November 2024, with an average follow-up time of one year.

Data Collection

Data collection was performed over one month. Medical information, including demographic, clinical, and laboratory data, was retrospectively extracted from electronic medical records. Variables collected included past medic al history, surgical history, clinical presentation, thyroid status, thyroid function tests, autoimmune markers, fine needle aspiration findings, imaging studies, and treatment modalities. Pathological data were independently reviewed by an expert pathologist using specimen slides.

Laboratory and Imaging Assessments

Comprehensive laboratory evaluations were conducted to assess thyroid function, autoimmune markers, and general health status. Thyroid function tests included thyroid-stimulating hormone and free thyroxine. Autoimmune markers measured included thyroid peroxidase antibodies and thyroglobulin antibodies. Additional tests included viral screenings and hemoglobin levels (complete blood count). Imaging studies included preoperative ultrasound to evaluate thyroid morphology, with hypoechoic lesions defined as having reduced echogenicity relative to normal thyroid tissue, while very hypoechoic lesions exhibited even lower echogenicity compared to adjacent musculature (Figure 1). Computed tomography (CT) and positron emission tomography (PET) scans were performed to assess disease extent in selected cases.

Diagnostic Biopsy Procedures

A core needle biopsy was performed using a spring-loaded Tru-Cut biopsy needle (18G). All patients underwent core needle or surgical biopsy for accurate diagnosis and immunohistochemistry analysis for markers.

Treatment Modalities

Surgical intervention primarily served a diagnostic role rather than a curative approach, with excisional biopsy, thyroidectomy, or lobectomy performed for tissue diagnosis. Chemotherapy protocols included the CHOP regimen, consisting of cyclophosphamide (750 mg/m²), adriamycin (50 mg/m²), vincristine (1.4 mg/m²), and prednisolone (100 mg/day), often combined with rituximab (375 mg/m²) to enhance therapeutic efficacy.

Ethical Considerations

The study was approved by the ethical committee of the Kscien organization. The study adhered to the principles of the Declaration of Helsinki. Due to its retrospective nature, neither patient approval nor informed consent was required.

Statistical analysis

The data were analyzed using the Statistical Package for the Social Sciences (SPSS) software version 27.0. Quantitative data were presented as means and standard deviations. Qualitative data were expressed as frequency and percentages.

Results

Among the nine cases, seven (77.8%) were female and two (22.2%) were male, with male-female ratio was 1:3.5. The mean age of patients was 60.78 ± 12.53 years. Clinically, anterior neck swelling was the most common presentation, observed in six cases (66.7%), while one case (11.1%) was on follow-up for preexisting thyroid conditions. The CT imaging revealed locally invasive thyroid masses involving the trachea, retrosternal space, or esophagus in three cases (33.3%), three cases (33.3%) had no available CT data. A history of prior thyroid surgery was noted in only one case (11.1%) (Table 1).

Seven (77.8%) cases received R-CHOP chemotherapy, with six (66.7%) completing six or more sessions. Total thyroidectomy was performed in one case (11.1%). Histopathological examination confirmed B-cell lymphoma in eight cases (88.9%) and marginal zone lymphoma in one case (11.1%). Thyroid function testing revealed TSH abnormalities in four cases (44.4%), with one (11.1%) presenting significantly elevated TSH levels (100.0 mIU/L) (Table 2).

Thyroid function status was euthyroid in four cases (44.4%), hypothyroid in three cases (33.3%), and hyperthyroid in one case (11.1%). Nodule location based on ultrasound was left-sided in four cases (44.4%), right-sided in three cases (33.3%), and bilateral in two cases (22.2%). The TI-RADS (Thyroid Imaging Reporting and Data Systems) classification showed that five cases (55.6%) were TI-RADS 5, while two (22.2%) were TI-RADS 4. The mean Free T4 and TSH levels were 11.93 ± 6.02 ng/dL and 19.31 ± 36.36 mIU/L, respectively. Regarding follow-up outcomes, four cases (44.4%) showed no recurrence, and two (22.2%) resulted in mortality (Table 3).

Discussion

Primary thyroid lymphoma is confined to the thyroid gland, with or without local lymph node involvement in the neck. There is no evidence of distant metastasis at the time of initial diagnosis. Epidemiological studies have consistently shown a higher prevalence of primary thyroid lymphoma (including NHL) in females compared to males, with a female-to-male ratio ranging from 1.8 to 4.4:1, predominantly affecting individuals in their fifth to eighth decades of life [9,10]. In line with these findings, the present study also noted a female predominance, a female-to-male ratio of 3.5:1, and an average age of 60.78 years.

The primary risk factor for primary thyroid lymphoma, including NHL, is Hashimoto's thyroiditis, which significantly increases the likelihood of developing it by 40 to 80 times. Despite this elevated risk, only 0.6% of individuals with Hashimoto’s thyroiditis go on to develop primary thyroid lymphoma [11,12]. The condition is predominantly associated with hypothyroidism, especially in the context of Hashimoto's thyroiditis, whereas cases of primary thyroid lymphoma occurring in hyperthyroid or euthyroid states are rare. This association is thought to arise due to the thyroid’s lack of native lymphoid tissue, which may accumulate due to chronic antigenic stimulation in Hashimoto’s thyroiditis, leading to lymphoid infiltration and the subsequent risk of lymphoma [10]. In the present study, of the nine cases of NHL, 5(55.6%) were euthyroid or hyperthyroid, with four patients being euthyroid and one hypothyroid. This supports the notion that while hypothyroidism is commonly associated with NHL, other thyroid states, including euthyroid and hyperthyroid, can also occur in these cases.

Patients with thyroid NHL typically present with a rapidly enlarging cervical mass that remains mobile during swallowing. This thyroid enlargement may result in compressive symptoms, including dysphagia, dyspnea, and hoarseness [13,14]. The mass can sometimes exert pressure on venous structures, leading to facial puffiness or swelling. Furthermore, lymphoma infiltration of the thyroid can induce hypothyroidism, manifesting as fatigue, cold intolerance, and dry skin. Additionally, systemic symptoms commonly associated with lymphoma, such as fever, night sweats, unexplained weight loss, and generalized pruritus, may also be observed [15]. In the current study, anterior neck swelling was the most common presentation, observed in six cases (66.7%). The high prevalence of anterior neck swelling in this study likely reflects the tumor's location in the thyroid, causing significant local enlargement and compressive effects.

Diagnosis of NHL of the thyroid necessitates a multifaceted approach, integrating clinical findings, advanced imaging techniques, and definitive tissue sampling. Imaging modalities such as ultrasound and CT scans are crucial in identifying thyroid abnormalities and associated lymphadenopathy [16]. Diagnosis is typically confirmed through histological examination and immunohistochemical results [10]. Identifying immunoglobin clonal gene rearrangements is essential for the differential diagnosis in patients with Hashimoto thyroiditis and a histologically benign lymphoepithelial lesion. Core needle biopsy or surgical excision is required to obtain sufficient tissue for accurate diagnosis and subtyping [17]. The present study used a comprehensive diagnostic approach, including ultrasound, CT scans, positron emission tomography scans, and fine needle aspiration cytology to detect thyroid abnormalities and associated lymphadenopathy. Core needle biopsy was performed when fine needle aspiration cytology alone was insufficient for diagnosis. Histopathological and immunohistochemical evaluations confirmed the presence of lymphoma.

Management of NHL of the thyroid typically involves a combination of approaches, including chemotherapy, radiation therapy, and, in some cases, surgery. The choice of treatment depends on the stage and grade of the lymphoma and the patient's overall health. In current practice, surgery mainly serves the purpose of obtaining tissue for diagnosis [2].  Radiotherapy, being highly effective for local disease control, is often utilized due to the radiosensitive nature of thyroid NHL. In contrast, chemotherapy targets occult or systemic disease, thereby enhancing long-term outcomes. The conventional CHOP regimen, comprising Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone, remains the standard treatment approach for systemic disease management [15,18]. Following three to six cycles of chemotherapy, radiation therapy is commonly administered to enhance disease control. The introduction of Rituximab has shown promising efficacy, particularly in elderly patients with diffuse large B-cell lymphoma. However, the role of surgical intervention remains debated [19]. Several factors influence prognosis, including patient age, tumor grade, and disease stage. Notably, mucosa-associated lymphoid tissue lymphoma generally exhibits a more favorable prognosis than large B-cell lymphoma, and outcomes are typically better in pediatric and young adult patients [20].

Recent studies on outcomes of primary thyroid lymphoma underscore substantial prognostic heterogeneity influenced by histopathological classification, therapeutic approach, and clinical factors. A population-based study of 1,408 primary thyroid lymphoma (including NHL) patients reported a median survival of 9.3 years, with multivariate analysis identifying advanced age, disease stage, histological subtype, and treatment modality as independent prognostic determinants [3]. Diffuse large B-cell lymphoma, the most prevalent subtype comprising approximately 68% of cases, exhibits variable 5-year survival rates between 45% and 90%, contingent on treatment protocols [4]. Notably, combined-modality therapy, particularly rituximab-based immunochemotherapy with radiation, has significantly enhanced prognosis, achieving 5-year overall and progression-free survival rates of 81.2% and 77.8%, respectively, compared to monotherapy approaches. In contrast, indolent subtypes such as mucosa-associated lymphoid tissue lymphoma demonstrate intermediate 5-year survival rates of approximately 62%, though they remain susceptible to persistent recurrence, unlike aggressive variants, which exhibit cure probabilities exceeding 90% after three years of remission [9]. Molecular analyses have further elucidated distinct evolutionary pathways underlying thyroid lymphoma relapse, providing insight into the observed variations in treatment response and clinical outcomes [21]. These findings collectively support the development of risk-adapted treatment algorithms, highlighting the necessity of histology-directed, multimodal therapeutic strategies to optimize survival while mitigating treatment-associated morbidity in this rare lymphoproliferative malignancy [22].

This retrospective case series of primary thyroid B-cell NHL is subject to several limitations. The short follow-up period of one year restricts the ability to evaluate long-term outcomes, recurrence patterns, and survival rates. Additionally, as a single-center study, the findings may lack broader applicability across different healthcare settings. The heterogeneity in treatment modalities, coupled with the absence of molecular and genetic analyses, further limits insights into the pathophysiology of the disease and optimal therapeutic strategies.

Conclusion

This study underscores the significance of early diagnosis and tailored treatment for primary thyroid NHL. The findings highlight the variable thyroid function and treatment responses, underscoring the need for personalized approaches to optimize patient outcomes.

Declarations

Conflicts of interest: The author(s) have no conflicts of interest to disclose.

Ethical approval: The study was approved by the ethical committee of the Kscien organization (No.32).

Patient consent (participation and publication): Written informed consent was obtained from patients for publication.

Source of Funding: Smart Health Tower.

Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.

Acknowledgements: None to be declared.

Authors' contributions: AMS and SFA were significant contributors to the conception of the study and the literature search for related studies.  RMA, HOB, IJH, DOK, ROM and SHH were involved in the literature review, the study's design, the critical revision of the manuscript, they participated in data collection. AMM, HAA, and AAQ were involved in the literature review, study design, and manuscript writing. AJQ was the radiologists who performed the assessment of the cases. AMA was the pathologist who performed the histopathological diagnosis. AMS and SHH confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.

Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data.

Data availability statement: Not applicable