Case Report Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 24, 2024; 15(10): 1324-1332
Published online Oct 24, 2024. doi: 10.5306/wjco.v15.i10.1324
Cervical myeloid sarcoma as an initial clinical manifestation: Four case reports
Jin-Ke Li, Dan-Dan Zhang, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Xiao-Xue Wang, Department of Health Management, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Jia-Jun Fu, Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
ORCID number: Dan-Dan Zhang (0000-0002-6584-5106).
Author contributions: Li JK wrote and edited the manuscript; Fu JJ and Wang XX collected the patients’ clinical data; Zhang DD conceptualized the paper and supervised its completion.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dan-Dan Zhang, Doctor, PhD, Associate Professor, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. zhangdd@sj-hospital.org
Received: March 23, 2024
Revised: August 26, 2024
Accepted: September 19, 2024
Published online: October 24, 2024
Processing time: 189 Days and 22.8 Hours

Abstract
BACKGROUND

Cervical myeloid sarcoma (MS) is a rare hematological malignancy characterized by the formation of extramedullary soft tissue masses in the cervical region. Due to its uncommon presentation in the female reproductive system, cervical MS poses significant diagnostic and therapeutic challenges. Consequently, there is a pressing need for more research and clinical experience to better understand, diagnose, and manage this condition effectively.

CASE SUMMARY

This report details four cases, the diagnostic process, treatment strategy, and outcomes, discussing cervical MS as an initial clinical manifestation. The disease exhibits varied clinical presentations, such as irregular vaginal bleeding and palpation of cervical masses. The treatment approaches discussed include neoadjuvant chemotherapy, surgery, and postoperative chemotherapy, though managing the disease remains challenging. The report also features a comprehensive literature review that underscores the importance of immunohistochemistry for accurate diagnosis, identifying key markers, including myeloperoxidase, cluster of differentiation (CD) 68, and CD43, stressing the need for further research to improve treatment strategies and prognosis.

CONCLUSION

Immunohistochemical diagnosis and tailored therapeutic strategies are essential. Further research is crucial in improving outcomes and developing effective treatment protocols.

Key Words: Cervical myeloid sarcoma; Hematologic malignancy; Clinical characteristics; Diagnosis; Treatment; Case report

Core Tip: Cervical myeloid sarcoma is rare but can indicate the presence of acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms. Immunohistochemistry is pivotal in diagnosing and differentiating myeloid sarcoma and the absence of cluster of differentiation (CD) 20 and CD3 can help distinguish it from lymphoma. Systemic chemotherapy is the most common treatment with some patients also undergoing surgery or radiation therapy. The literature indicates that allogeneic hematopoietic stem cell transplantation is a critical strategy for long-term survival.



INTRODUCTION

Malignant tumors of the hematopoietic system can manifest as extramedullary soft tissue masses, and myeloid sarcoma (MS) is a rare clinical presentation. It refers to the formation of tumors outside the bone marrow by immature myeloid cells, with or without concurrent marrow involvement[1]. In most cases, it is associated with myeloid disorders, such as acute myeloid leukemia (AML), but there are instances where it presents solely as an extramedullary myeloid tumor. MS can affect multiple tissues and organs throughout the body, with rare occurrences in the cervix and reproductive organs[2,3].

This report presents four cases of cervical MS diagnosed at our hospital and provides an in-depth analysis. Additionally, a comprehensive review and analysis of the relevant literature from the past decade was conducted, aiming to enhance understanding of this rare disease and offer valuable insights for clinical diagnosis and treatment. The literature search from January 2013 to December 2022 was performed on PubMed (MEDLINE) and China National Knowledge Infrastructure. Our search strategy involved a combination of key terms, including “myeloid sarcoma”, “Granulocytic Sarcoma”, “Chloroma”, “extramedullary myeloid cell tumor”, “cervix neoplasm”, “cervical cancer” and “cervix cancer”. Only full-text articles were included in our study to ensure a comprehensive review of relevant information.

CASE PRESENTATION
Chief complaints

Case 1: A 49-year-old woman presented with a 2-month history of irregular vaginal bleeding.

Case 2: A 54-year-old postmenopausal woman presented with irregular bleeding.

Case 3: A 46-year-old woman presented with irregular bleeding after menstruation.

Case 4: A 48-year-old female presented with 4 months of irregular vaginal bleeding.

History of present illness

Case 1: The ultrasound examination performed at the local hospital indicated a hypoechoic cervical mass. A colposcopic biopsy indicated diffuse infiltration of small cells in the cervical stroma. Immunohistochemistry (IHC) results were as follows: Cytokeratin (CK) (-), P63 (-), cluster of differentiation (CD) 20 (-), CD3 (-), CD43 (+), and myeloperoxidase (MPO) (-). The pathological diagnosis was cervical MS.

Case 2: The patient presented with irregular vaginal bleeding for 2 months after being postmenopausal for 1 year, with a volume less than that of previous menstrual periods and a dark red color.

Case 3: The patient experienced vaginal bleeding for 2 months after menopause. Examination revealed a mass on the anterior lip of the cervix, and a biopsy performed under colposcopy showed severe chronic inflammation with erosion and lymphoid tissue hyperplasia in the cervical tissue.

Case 4: The patient was found to have a cervical mass, and a cervical biopsy suggested a diagnosis of undifferentiated carcinoma, which suggested undifferentiated carcinoma. IHC results were as follows: Ki-67 60% (+), high molecular weight-CK, carcinoembryonic antigen, P40, CK5/6, P16, CD56, and chromogranin A were all negative. Despite undergoing subsequent chemotherapy (uterine artery interventional chemotherapy: Cisplatin 40 mg, vincristine 2 mg; Intravenous chemotherapy: Paclitaxel 135 mg/m² on day 1, cisplatin 70 mg/m² on day 1), there was no significant change in the tumor.

History of past illness

Cases 1, 3, and 4: Generally healthy.

Case 2: The patient had a 3-year history of hypertension without antihypertensive treatment, and no other medical history.

Personal and family history

The patient denied a family history of malignant tumors or hematologic disorders.

Physical examination

Case 1: Gynecological examination revealed that the vaginal vault was absent, the cervix was markedly enlarged, firm with contact bleeding.

Case 2: Gynecological examination revealed a firm, 6 cm mass on the posterior lip of the cervix with limited mobility.

Case 3: Gynecological examination revealed a firm, 3 cm mass on the cervix with surface erosion, and bleeding on palpation.

Case 4: Gynecological examination showed the disappearance of the anterior vaginal vault and a firm, 7.0 cm × 5.0 cm mass on the posterior lip of the cervix extending into the lumen. The tissue was gray-white and friable, with thickening of the parametrium.

Laboratory examinations

Case 1: Peripheral blood tests and cervical cytology were unremarkable. The patient declined a bone marrow biopsy procedure (BMP).

Case 2: Cervical cytology was normal. Blood tests showed an elevated white blood cell (WBC) count of 50.8 × 10^9/L. Peripheral blood morphology analysis revealed decreased neutrophils (15%), lymphocytes (7%), and monocytes (1%), with 76% abnormal WBCs, suggesting acute leukemia. BMP showed highly active marrow proliferation (90%) and diffuse proliferation of blast cells, with medium-sized cells and abundant cytoplasm. Scattered late erythroblasts were observed, and megakaryocytes were common, predominantly with segmented nuclei. Reticulin staining showed a fibrosis stage of modified fibrosis grade 1; Periodic acid-Schiff staining was positive. IHC results showed MPO (+), CD34 (-), CD117 (+), CD20 (-), CD3 (-), and terminal deoxynucleotidyl transferase (TdT) (-), consistent with AML. Chromosome analysis showed a karyotype of 46XX with no clonal abnormalities; fusion gene testing was negative for the promyelocytic leukemia/retinoic acid receptor alpha gene fusion. Flow cytometry identified 74.09% abnormal myeloid blasts, consistent with the AML phenotype, with AML-with maturation (M2) as the likely diagnosis after excluding recurrent genetic abnormalities.

Case 3: Peripheral blood tests and cervical cytology were unremarkable.

Case 4: The squamous cell carcinoma antigen was 5.35 mg/mL. Cervical cytology did not show any abnormalities.

Imaging examinations

Case 1: Computed tomography (CT) identified an 8.8 cm × 7.4 cm cervical mass (Figure 1A).

Figure 1
Figure 1 Computed tomography imaging. A: Computed tomography (CT) image prior to treatment; B: CT image following initial chemotherapy session, showing a reduction in the lesions.

Case 2: Ultrasound revealed a full cervical shape with a hypoechoic mass in the posterior lip, measuring approximately 6.4 cm × 5.1 cm × 6.1 cm.

Case 3: Ultrasound examination revealed a cervical mass, showing a hypoechoic lesion measuring 3.0 cm × 2.5 cm.

Case 4: Pelvic enhanced magnetic resonance imaging (MRI) showed a significantly enlarged cervical canal containing a mass measuring 7.2 cm × 4.5 cm. There was involvement of endometrium and the upper one-third of the vagina, with multiple enlarged lymph nodes adjacent to the bilateral iliac vessels.

FINAL DIAGNOSIS
Case 1

Based on physical examination, imaging studies, and pathological evaluation, the diagnosis was cervical MS.

Case 2

The initial diagnosis was a cervical mass of uncertain nature, leading to a cervical biopsy. Histopathological evaluation (Figure 2) and IHC (positive for CD117 and MPO; negative for CD34, TdT, CD20, PAX5, CD3, CD7, Cg-A, CK, and Syn) confirmed the diagnosis of cervical MS, potentially resulting from AML.

Figure 2
Figure 2 Pathological examination microscopy images revealed medium-sized tumor cells with irregular nuclei and frequent mitotic figures. A: Hematoxylin-eosin staining at × 200 magnification; B: Hematoxylin-eosin staining at × 400 magnification.
Case 3

A conization was performed, which removed the mass entirely. Postoperative pathological examination showed diffuse proliferation of atypical cells with large cell bodies, moderate to abundant cytoplasm, and oval or slightly irregular nuclei with fine chromatin. IHC results were: CD43 (+), CD117 (+), MPO (70% +), lysozyme (focal +), Ki-67 (50% +), and negative for PAX5, CD34, CD7, TdT, and CD2 (Figure 3). These findings suggest a hematological malignancy consistent with MS, but further BMP showed no abnormalities.

Figure 3
Figure 3 Immunohistochemical staining of cervical myeloid sarcoma. A: Myeloperoxidase (70% +); B: Cluster of differentiation (CD) 43 (100% +); C: Ki-67 (50% +); D: CD34 (-).
Case 4

The patient underwent tumor debulking surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and enlarged lymph node biopsy). Postoperative pathology revealed diffuse infiltration of atypical lymphoid cells throughout the cervical tissue. The cells were medium-sized with pale-staining cytoplasm, round and irregular nuclei, fine chromatin, occasional small nucleoli, and frequent mitotic figures. Tumor emboli were observed in lymphatic vessels but not in blood vessels. Pelvic lymph nodes showed metastasis: 1/9 on the left and 1/4 on the right. IHC showed lymphocyte common antigen (+), P16 (+), CD68 (+), and CD117 (+), with CK5/6, CK panel, PAX5, TdT, CD3, CD20, CD15, and CD34 all negative, consistent with cervical MS. Further BMP showed no abnormalities.

TREATMENT
Case 1

After initial chemotherapy with the DA regimen (daunorubicin on days 1-3 and cytarabine on days 1-7, for two cycles), a reduction in the mass’s size was observed (Figure 1B). Subsequent surgical management included a radical hysterectomy and pelvic lymph node dissection. The gross pathology revealed a solid, finely textured, green lesion infiltrating the entire cervical wall, and microscopic examination showed medium-sized tumor cells with irregular nuclei and frequent mitotic figures. IHC results were as follows: TdT (focal +), MPO (+), CD34 (-), CD68 (+), and Ki-67 (> 50% +). The diagnosis of cervical MS was confirmed. A BMP performed postoperatively was unremarkable.

Case 2

The patient was treated with cytarabine to lower the WBC count, which decreased to 11.56 × 109/L. However, the patient refused further chemotherapy.

Case 3

11 days postoperatively, a recurrent cervical mass was detected. The patient received chemotherapy with the DA regimen for two cycles, followed by total hysterectomy and lymph node dissection. Pathological examination of the resected tissue revealed an irregular, slightly protruding mass with a gray-white to gray-brown soft, delicate texture, infiltrating the entire cervical wall, the cervical canal, and the cervical dome. No tumor emboli were found in the vessels, and pelvic lymph nodes showed no metastasis. IHC was positive for lysozyme, CD43, CD117, CD34, and CD99, with focal positivity for MPO and Ki-67 at 50%. The diagnosis of cervical MS was confirmed. Postoperatively, the patient continued with 4 cycles of DA regimen chemotherapy.

Case 4

The patient received four cycles of mitoxantrone 10 mg on days 1-3 and cytarabine 240 mg on days 1-7 intravenous chemotherapy postoperatively.

OUTCOME AND FOLLOW-UP
Case 1

Despite further chemotherapy (cytarabine and etoposide), the patient developed metastatic disease in the breast, vulva, and vagina and succumbed to the disease 22 months after diagnosis.

Case 2

The patient declined recommended chemotherapy and tragically passed away 1.5 months after discharge.

Case 3

The patient continued with four additional cycles of DA regimen chemotherapy and remains disease-free after 3 years of follow-up.

Case 4

The tumor progressed with pulmonary metastases. The patient chose to discontinue treatment and died 9 months later.

DISCUSSION

MS, or granulocytic sarcoma, is a neoplasm arising from primitive or immature granulocytic cells outside the bone marrow or bone tissue. This condition can precede, coincide with, or manifest as the initial sign of AML, myelodysplastic syndrome, or myeloproliferative neoplasms. It may also herald an AML relapse, sometimes with a considerable time lag between the occurrence of MS and the onset of AML, which can range from months to years. While MS commonly affects sites, such as the skull, paranasal sinuses, sternum, ribs, vertebrae, pelvic bones’ subperiosteal regions, lymph nodes, and skin, its occurrence in the cervix is exceedingly rare, particularly when it presents as an isolated mass without accompanying leukemia.

We conducted a retrospective analysis, searching for clinical and pathological data, treatment protocols, and prognosis of patients with cervical MS reported in the domestic and international literature over the past 10 years. A total of 21 complete cases were included in the comprehensive data (Table 1)[4-21]. In terms of treatment, 17 cases received systemic chemotherapy, with seven of these also undergoing concurrent surgical intervention, either in the form of total or radical hysterectomy. Additionally, three cases received radiotherapy. The follow-up periods varied widely, extending from 1 to 91 months, with a median follow-up duration of 8 months. At the conclusion of the follow-up period, 12 patients were alive, while eight had unfortunately passed away. Immunohistochemical analysis of the 20 patients revealed a high positivity rate for key markers: MPO was positive in all 20 tested cases (100.0%), CD68 was positive in 7 out of 10 cases (70.0%), lysozyme in 8 out of 9 cases (88.9%), CD43 in all 15 tested cases (100.0%), CD117 in 11 out of 15 cases (73.3%), CD34 in 9 out of 16 cases (56.3%), CD15 in 3 out of 9 cases (33.3%), CD99 in 5 out of 7 cases (71.4%), and both CD20 and CD3 were not expressed in any of the 17 and 18 cases tested, respectively.

Table 1 Information on patients with cervical myeloid sarcoma reported in the current study and in the literature (2013-2023).
Ref.
Published year
Age
Tumor size
Symptoms
With/without AML at diagnosis or previous
Initial treatment
Progression and subsequent treatment
Follow-up (months)
Outcome
Case 1-498.8Vaginal bleedingNoDA chemotherapy + surgery + chemotherapyMulti-site recurrence22Death
Case 2-546.4Vaginal bleedingYesWithdrawing treatment-1.5Death
Case 3-463Vaginal bleedingNoDA chemotherapy + surgery + DA chemotherapy-36Survival
Case 4-487.2Vaginal bleedingNoChemotherapy + surgery + MA chemotherapyLung metastasis9Death
Jiang et al[4]2015661.2Vaginal bleedingNoSurgery + IA chemotherapy + radiotherapy-6Survival
Wu and He[5]2014258.4Vaginal bleedingNoIA chemotherapy-3Survival
Liu et al[6]2013278.5Contact bleedingNoAbandoning treatment after surgery-15Survival
Wang et al[7]2014436Contact bleedingNoDA chemotherapy + intrathecal injection-7Survival
Peng et al[8]20193911Vaginal bleedingNoSurgery + chemotherapy-2Survival
Zuo et al[9]2016424Vaginal bleedingNoSurgery + DA chemotherapyTransformation into AML during chemotherapy12Death
Zuo et al[9]2016514.5NoNoE-CHOP chemotherapy + CHEP chemotherapy + surgery + DA chemotherapyGingival metastases at 55 months, with radiation and chemotherapy + bone marrow transplant91Survival
Zhang and Cai[10]2017236.9Vaginal bleedingDiagnosed with AML-M2 5 years agoMA chemotherapy-1Survival
Jiang et al[11]201728-Vaginal bleedingNoChemotherapyProgressed into AML-M2a within 5 months20Death
Jiang et al[12]201749-Vaginal bleedingNoWithdrawing treatment-5Death
Jiang et al[12]201743-Vaginal bleedingNoRadiotherapy + chemotherapy-7Death
Feng et al[13]2017572.5Contact bleedingNoWithdrawing treatment-6Survival
Yu and Ye[14]2013284.5Vaginal bleedingNoIA chemotherapy-18Death
Gill et al[15]2013362Vaginal bleedingNoChemotherapy-16Survival
Abu Saadeh et al[16]2015405NoDiagnosed with AML 11 years agoSurgery + chemotherapy + radiotherapy-21Survival
Mishra et al[17]2018362Increased menstrual flowYesChemotherapyMultiple lymph node infiltrations detected on the 31st day of chemotherapy1.5Death
Ucar et al[18]201423-Vaginal bleedingDiagnosed with AML 3 years agoChemotherapy-2Survival
Gui et al[19]2019466Contact bleedingNoSurgery + chemotherapyMulti-site recurrence, without AML21Death
Gui et al[19]2019396.9Vaginal bleedingNoSurgery + chemotherapyProgressed into AML within 5 months26Death
Shatilova et al[20]2021497.6Vaginal bleedingUncertainDA chemotherapyBone marrow transplantation4Survival
Choi et al[21]2022493.4Vaginal bleedingDiagnosed with MDS, but not AMLSurgery---

The clinical presentation of cervical MS often includes vaginal bleeding (71.41% of cases in this series), palpable cervical masses, or cervical enlargement. A salient example is the first case in this report, where the patient presented with a bleeding, enlarged cervix, and the gross specimen exhibited a characteristic grass-green coloration. This color is due to MPO within the tumor tissue, which fades rapidly in air but reappears upon exposure to hydrogen peroxide, leading to the term “green sarcoma”.

Microscopically, MS is composed of a heterogeneous population of primitive granulocytic cells, neutrophils, and their precursors. It can mimic lymphoma, presenting with a diffuse pattern of small, lymphocyte-like cells. These cells vary in size, show slight pleomorphism, have minimal cytoplasm, and often display eosinophilia. The nuclei are typically irregular, round, or oval with a prominent nuclear membrane, fine chromatin, and indistinct nucleoli, alongside frequent mitotic figures. Immature eosinophilic granulocytes may be sparsely interspersed among the tumor cells. IHC is pivotal in diagnosing and differentiating MS, with markers, such as CD68/KP1, MPO, CD117, CD99, CD68/PG-M1, lysozyme, CD34, TdT, CD56, and CD30 being commonly utilized[22]. MPO, a marker for MS, may be negative in poorly differentiated tumors. The absence of CD20 and CD3, which are markers for T and B cells, can help distinguish MS from lymphoma. CT and MRI are valuable diagnostic tools, with positron emission tomography-computed tomography playing a significant role in the early detection and assessment of tumor burden[23]. Moreover, some patients exhibit cytogenetic abnormalities and gene mutations[24,25].

No one-size-fits-all treatment protocol for MS exists, encompassing systemic chemotherapy, local therapy, hematopoietic stem cell transplantation, molecular targeting, and immunotherapy[26]. The suggestion by Lee et al[27] that an early, multimodal approach to diagnosis and intensive combination therapy may mitigate the risk of AML development in MS is noteworthy. Although the treatment of MS remains a subject of debate, anthracycline-based regimens combined with cytarabine are frequently utilized. In this study, 24 cases received systemic chemotherapy, with some also undergoing surgery or radiation therapy. The literature indicates that allogeneic hematopoietic stem cell transplantation is a critical strategy for long-term survival in patients with MS, as supported by a retrospective study demonstrating favorable outcomes and advocating for transplantation following the initial remission[28].

CONCLUSION

In essence, cervical MS is a rare hematological malignancy affecting the female reproductive system. While it may present as a localized condition, it is recognized as a manifestation of a more extensive systemic disease. The therapeutic management of cervical MS diverges from the standard surgical and radiation treatments typically employed for cervical squamous cell carcinoma, with a primary focus on systemic chemotherapy. Owing to the rarity of this disease, our knowledge regarding its optimal treatment strategies and prognostic indicators remain limited, highlighting the imperative for additional research to expand our understanding and improve patient outcomes.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Oncology

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade C

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Dey P S-Editor: Fan M L-Editor: A P-Editor: Zhao YQ

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