In the resplendent, yet oft-overlooked periphery of oncologic literature, the gynaecological organs serve as an unaccustomed milieu for neoplasms classically regarded as haematologic or neuroendocrine in provenance. B-cell lymphomas and neuroendocrine tumours (NETs), when transposed from their orthodox anatomical dominions into the uterine corpus, cervix, ovary, or vulva, orchestrate an intricate ballet of pathological ambiguity and therapeutic trepidation. Though rare—accounting for <1% of all genital tract malignancies [1–3]—these entities demand an elevation of diagnostic vigilance and therapeutic synchrony.

Primary lymphomas of the ovary or uterus are exceedingly uncommon, yet possess aggressive biological behaviour and are often indistinguishable from epithelial ovarian tumours [4–6]. Similarly, high-grade neuroendocrine carcinomas (NECs) of the cervix mimic squamous cell carcinoma clinically but are biologically more virulent and resistant to conventional therapy [7–10].

This study endeavours to unravel the cumulative histopathological, surgical, and therapeutic experience gleaned from a focused cohort over three years within the Department of Gynaecology primarily & integrating with the Departments of Pathology , Radiology, Radiation Oncology , Community Medicine of a superspeciality hospital, with the aim of establishing a foundational discourse in this otherwise sparsely documented terrain.

Aims and Objectives

To classify B-cell neoplasms and neuroendocrine tumours confined to gynaecological organs according to WHO and FIGO standards.

To delineate their histopathological and immunohistochemical landscapes, including key markers and proliferation indices.

To evaluate the surgical and chemotherapeutic modalities applied and analyse outcome metrics.

A retrospective cohort study was conducted in the Department of Gynaecology, encompassing 200 women diagnosed between January 2019 and December 2022. Inclusion criteria required histologically confirmed B-cell lymphoma or NET of any female reproductive organ.

Data Collection Parameters

Clinical history, age, parity, symptoms, tumour location.

Histopathology with WHO 2020 classification.

IHC profile: CD20, CD79a, BCL2, Ki-67 for lymphomas; Chromogranin A, Synaptophysin, CD56, p53 for NETs.

Imaging (MRI, PET-CT).

FIGO stage, surgical notes, adjuvant treatment.

Follow-up outcomes.

Statistical Analysis: SPSS v26.0 was used for data analysis. Survival functions were analysed using Kaplan-Meier, and prognostic factors with multivariate Cox regression. Statistical significance was set at p<0.05.

The mean age of presentation across the entire cohort was 52.3 ± 9.6 years, with a positively skewed distribution favouring postmenopausal women (60.2%), thereby indicating a potential hormonal or immunosenescent predisposition in the pathogenesis of these neoplasms. Notably, 39% of tumours localised to the ovary, followed by 34% to the cervix, delineating the ovarian tissue as the most frequent anatomical nidus.

Subtype-Specific Histopathological Proliferation Indices and Marker Expression

B-cell Neoplasms (n = 89)

The histomorphological evaluation revealed that DLBCL was the predominant subtype (41.6%), exhibiting a mean Ki-67 index of 71.3%, reflective of a hyperproliferative state. This significantly exceeded the proliferative indices of follicular lymphoma (32.5%) and marginal zone lymphoma (28.9%), with the difference reaching statistical significance (p < 0.01, ANOVA). The CD20 immunopositivity was universally present in DLBCL and Burkitt cases (100%), whereas slightly reduced in marginal zone (92%) and mantle cell variants (87%), indicating a relative heterogeneity in B-cell lineage differentiation.

Table 1: Neuroendocrine Tumours (n = 111)

NETs presented with a mean Ki-67 index of 54.8% across all grades, but when stratified by histological grading:

G3 tumours (cervix NEC, endometrial NEC) had Ki-67 > 70% (p < 0.001), G1–G2 tumours (ovarian carcinoid) showed significantly lower indices, mean 10.4% (p < 0.0001, t-test). Moreover, overexpression of chromogranin A and synaptophysin was significantly more frequent in cervical NECs (89%) than in ovarian carcinoids (64%) (p = 0.02, Chi-square test), suggesting a differential neuroendocrine marker profile according to anatomical origin and tumour grade.

Table 2: Therapeutic Outcomes and Surgical Statistics

Therapeutic Outcomes and Surgical Statistics

Of the total cohort: 63% of NET patients underwent radical surgical excision (n=70), compared to only 27% of B-cell lymphoma cases (n=24). This disparity was found to be statistically significant (p < 0.001, Fisher’s exact test), owing to the primarily systemic nature of lymphomas. Complete surgical resections (R0) were achieved in 58% of NET surgeries, which showed a 2.3-fold reduction in recurrence risk (Hazard Ratio: 0.44; 95% CI: 0.27–0.72; p = 0.001). Pelvic exenteration was performed in 6 NEC cases, with a postoperative complication rate of 33.3%, but yielded a recurrence-free survival (RFS) benefit in patients with locally advanced disease (p = 0.019).

Recurrence Dynamics and Survival Indices

Overall recurrence rate: 20.5% (n=41), NETs: 27/111 (24.3%), B-cell lymphomas: 14/89 (15.7%), Cervical NECs had the highest recurrence rate (31.9%) among all subtypes, significantly correlated with Ki-67 > 70% and p53 mutations (p = 0.003 and p = 0.004 respectively, Cox regression).

Overall 3-year survival (OS): Total cohort: 66.8%, B-cell lymphomas: 69.2%, NETs: 64.4%. The Kaplan-Meier survival curves demonstrated significant divergence by histologic subtype (Log-rank test, χ² = 11.7, df = 3, p = 0.008), with low-grade NETs (G1–G2) achieving 82% OS, and cervical NECs falling below 60% at 3 years.

Additionally, multivariate Cox proportional hazard modelling revealed: Ki-67 > 60% (HR = 2.64; p = 0.004) Incomplete resection (HR = 3.08; p = 0.001), p53 mutation positivity (HR = 2.37; p = 0.003). These were independent predictors of reduced OS, even after adjusting for FIGO stage and tumour site.

Table 3: Correlation Matrix Summary (Spearman’s ρ)

Predictive Model Performance

Using a logistic regression model integrating Ki-67 index, IHC marker profile, surgical margins, and tumour site, the prediction of 3-year recurrence achieved: Sensitivity: 84.7%, Specificity: 79.2% and AUC (ROC curve): 0.865 (95% CI: 0.798–0.911), indicating excellent discriminative capacity..

The intrusion of B-cell neoplasms and neuroendocrine tumours (NETs) into the anatomical sanctum of the female genital tract—ordinarily the domain of epithelial malignancies—presents a formidable paradigm shift in both gynecopathological nosology and therapeutic execution. Though such tumours are numerically sparse, their clinical import is disproportionately profound, owing to their cryptic presentations, diagnostic elusiveness, and often pernicious biological trajectories [1–3].

Primary lymphomatous infiltrations of the ovary and uterine corpus—particularly diffuse large B-cell lymphoma (DLBCL)—have proven to be veritable masqueraders of epithelial ovarian carcinoma, both radiologically and intraoperatively. The absence of pathognomonic symptoms and a tendency to be diagnosed postoperatively renders these lesions particularly insidious [4–6, 21]. Immunophenotyping, chiefly with CD20, CD79a, and BCL2, stands as the sine qua non of accurate delineation, further substantiated by Ki-67 proliferative indices that portend a dismal trajectory in high-grade variants [13, 23]. This study’s finding of a mean Ki-67 index of 71.3% in DLBCL affirms the proliferative aggression documented in prior seminal works [19, 26].

Of equal, if not greater, oncological concern are neuroendocrine tumours of the cervix and ovary, which in their high-grade forms—most notably small-cell neuroendocrine carcinoma (SCNEC) of the cervix—exhibit a proclivity for early lymphovascular permeation, nodal dissemination, and distant metastasis [7–10, 17]. The substantial representation of cervical NECs (42.3%) within our cohort echoes population-based epidemiological datasets that underscore the predilection of these tumours for the cervix, despite their embryologic incongruity therein [8, 9, 15]. The detection of p53 mutations, coupled with high Ki-67 (>70%) and elevated expression of chromogranin A and synaptophysin, further buttresses the assertion that cervical NECs are a distinct nosological entity meriting aggressive intervention [22, 24].

Therapeutically, the data herein consolidate the primacy of multimodal approaches, particularly in neuroendocrine pathologies. Radical surgical procedures—including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and even pelvic exenteration—demonstrated therapeutic utility in reducing tumour burden, especially when employed in early-stage or well-differentiated NETs [12, 16, 24]. Surgical cytoreduction conferred appreciable survival benefit, especially when complete resection (R0) was attained. In contrast, incomplete resections were statistically associated with inferior outcomes (p=0.001), thus corroborating oncological doctrines that emphasize the sanctity of margin clearance [25].

Chemotherapeutic regimens differed according to histology: B-cell neoplasms largely responded to the R-CHOP protocol, with an appreciable 3-year OS of 69.2%, consistent with reports from Ganjoo et al. and others [4, 20]. Conversely, NECs necessitated platinum-based regimens (cisplatin and etoposide), albeit with a slightly lower OS of 64.4%, reflecting their biological tenacity and resistance to monotherapy [15–17]. Radiotherapy played an adjunctive role predominantly in cervical NETs, although its efficacy as a standalone modality remains suboptimal. The inclusion of somatostatin analogues in low-grade ovarian NETs yielded encouraging results, particularly in hormonally active tumours, aligning with the conclusions of Modlin et al. [30].

The recurrence rate, pegged at 20.5%, was notably skewed toward cervical NECs (31.9%), thereby reaffirming their volatile natural history. The prognostic stratification of patients based on Ki-67 index (>60%, p=0.004), p53 aberrancy (p=0.003), and extent of resection reiterates the value of molecular and surgical precision in outcome determination [14, 18, 25].

Taken together, the findings unveil a compelling tapestry wherein histologic subtype, immunohistochemical phenotype, and surgical resectability interweave to forecast clinical outcome. Such a nuanced matrix defies the one-size-fits-all paradigm, urging instead for a bespoke algorithm of care, predicated on early recognition, molecular dissection, and maximal therapeutic aggressiveness.

In summation, this investigation not only reinforces previously described histopathological archetypes and therapeutic tenets but expands the purview by anchoring them within the topography of female reproductive oncology, hitherto regarded as an anomalous terrain for such neoplasms [2, 5, 11].

Within the rarefied realms of gynaecologic oncology, the incursion of B-cell lymphomas and neuroendocrine tumours constitutes a pathobiological anomaly of considerable consequence. Their scarcity belies their sinister potential, and their mimicry of more common gynaecologic malignancies demands that clinicians exercise a heightened degree of morphological suspicion. This study, by unravelling a comprehensive, multi-parametric profile of these neoplasms across 200 patients, serves to illumine the path for future diagnostic and therapeutic undertakings.

The histologic and immunophenotypic individuality of each tumour subtype—be it the relentless proliferation of high-grade DLBCL or the virulent dissemination of cervical NEC—necessitates an integrative therapeutic response. Immunohistochemistry remains the cornerstone of diagnostic affirmation, while radical surgery, when appropriately applied, offers meaningful survival dividends, especially in early-stage or low-grade presentations.

The statistically validated prognosticators—high Ki-67, p53 mutation, incomplete surgical resection—serve as guiding luminaries for risk stratification and tailored intervention. Furthermore, the data endorse the incorporation of targeted modalities such as somatostatin analogues, radiotherapy, and novel chemotherapeutic agents within a multimodal matrix.

Hence, the management of these tumours must transcend the paradigms of conventional gynaecologic malignancy and instead align with principles derived from haematologic and neuroendocrine oncology. The clinician must, therefore, adopt an interspecialty lens—drawing from haematopathology, surgical oncology, and endocrine therapeutics—to navigate this complex nosological territory.

In closing, the present inquiry articulates not merely a repository of statistical observations but a clarion call for algorithmic recalibration in the oncologic approach to gynaecologic B-cell neoplasms and NETs. It is only through such recalibration—anchored in morphological acumen, surgical precision, and molecular insight—that improved prognostication and therapeutic conquest may be realized.

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