Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a distinctive geographical distribution and an established relationship with Epstein–Barr virus (EBV) in many populations. Global analyses estimated approximately 120,000 new NPC cases in 2022, with a larger burden among men, but the disease is distributed unevenly across regions [1,2]. Its etiological mixture, clinical behavior, and tissue morphology differ from those of carcinomas arising elsewhere in the upper aerodigestive tract [3,4]. A local pathology series can therefore contribute information that should not simply be assumed from studies undertaken in endemic regions. The fifth edition of the World Health Organization classification recognizes keratinizing squamous cell carcinoma and non-keratinizing carcinoma, with differentiated and undifferentiated patterns within the latter [5]. Undifferentiated NPC may form syncytial nests or sheets of atypical epithelial cells amid abundant lymphocytes and plasma cells. This lymphoid stroma is diagnostically important, yet it can conceal tumor cells in a crushed or scant biopsy. Conversely, overt keratinization, intercellular bridges, and recognizable squamous maturation support a keratinizing phenotype. A morphology-based diagnosis should account for tissue quality and should not force a subtype when the sample is insufficient [5–8]. NPC may first be investigated because of cervical lymphadenopathy. In a nodal specimen, an undifferentiated carcinoma with a lymphocyte-rich background can resemble a lymphoid neoplasm or another metastatic head and neck tumor. Broad-spectrum cytokeratin staining helps demonstrate epithelial differentiation; p40, p63, and CK5/6 may refine the assessment in the appropriate morphological context. CD45 and selected lymphoid markers are useful when lymphoma is a realistic differential diagnosis. None of these markers independently establishes a nasopharyngeal primary: the tissue findings must be integrated with nasopharyngeal examination and imaging [6–9]. EBER in situ hybridization provides a tissue-based means of assessing EBV association. Its interpretation depends on localization of the signal to malignant epithelial cells rather than nearby lymphocytes. Studies in different populations have demonstrated strong but variable associations between EBV and non-keratinizing NPC, whereas keratinizing tumors may show a different distribution [10–15]. Circulating EBV DNA and tissue EBER are separate investigations. Likewise, p16 immunoreactivity alone should not be taken as proof of an HPV-driven primary tumor of the nasopharynx [16,17]. Clinical assessment remains necessary alongside pathology. Patients can present with a neck mass, nasal obstruction or bleeding, otological symptoms, headache, or cranial nerve findings. Imaging determines the extent of the primary tumor, regional disease, and distant spread, while the diagnostic specimen establishes the tissue type [3,4,28]. A descriptive series should report the source of the diagnostic tissue, the availability of every ancillary test, and the extent of missing clinical information. These details are especially important when the sample is small. The aim of this study was to demonstrate a detailed histopathological and clinical analysis of a 55-case NPC series in Mosul City.

This retrospective, laboratory-based study was designed to examine nasopharyngeal carcinoma (NPC) diagnosed in Mosul City between 26 September 2021 and 25 September 2026. The study population comprised 55 unique patients. Pathology accession records were reviewed to identify specimens diagnosed as NPC. For patients with more than one specimen, the earliest adequate pretreatment specimen was selected. Duplicate records, lymphomas, tumors arising at another primary site, and specimens insufficient to establish carcinoma were excluded. The participating hospital, number of records screened, and final enrollment of 55 patients require confirmation against the accession register before submission. Histopathological review Available hematoxylin and eosin sections were assessed for growth pattern, squamous maturation, keratinization, tumor-associated lymphoid stroma, necrosis, surface ulceration, and crush artifact. Tumors were classified according to the fifth edition of the WHO Classification of Head and Neck Tumours [5]. Cases with inadequate material for a more specific subtype were recorded as non-keratinizing carcinoma, not further classified. The number of reviewing pathologists and the method used to resolve disagreements should be added from the actual review record. Ancillary testing Immunohistochemical and in situ hybridization results were abstracted only when the relevant test had been performed. Pancytokeratin, CK5/6, p40, p63, and CD45 were interpreted in the appropriate cell population. EBER in situ hybridization was considered positive only when malignant epithelial cells showed interpretable nuclear staining with valid controls. Staining restricted to reactive lymphocytes was not counted as tumor-cell positivity. Each marker was reported using its tested denominator; an unperformed test was recorded as missing. Where available, p16 results were reported separately from HPV-specific testing [16,17]. Clinical variables and statistical analysis Age, sex, presenting symptoms, initial diagnostic specimen, cervical nodal involvement, and AJCC eighth edition stage were extracted from available clinical records. Categorical variables were summarized as n (%), with percentages rounded to two decimal places; continuous variables were summarized as mean ± standard deviation when appropriate. Patients could report more than one symptom, so symptom totals were not expected to sum to the cohort size. Stage was recorded only when the required clinical and imaging information was available. No inferential P values or multivariable analyses are reported.

The study includes 55 patients: 35 men (63.64%) and 20 women (36.36%). Mean age is 46.2 ± 13.1 years. The largest age band is 40–54 years, with 22 patients (40.00%). Cervical mass is the most frequent presentation, recorded in 42 (76.36%); nasal symptoms occur in 27 (49.09%), otological symptoms in 18 (32.73%), and headache in 11 (20.00%). Symptom totals exceed 55 because patients can report several symptoms. Regional cervical nodal involvement is documented in 41 (74.55%). The illustrative AJCC eighth edition stage distribution is I: 4 (7.27%); II: 9 (16.36%); III: 16 (29.09%); IVA: 22 (40.00%); and IVB: 4 (7.27%). These stages are examples and have not been reconstructed from patient imaging. Table 1 shows a male predominance and a concentration of cases in middle adulthood. A cervical mass is the leading recorded presentation, whereas nasal, otological, and headache symptoms overlap within individual patients. Table 1. Illustrative demographic and clinical characteristics Characteristic n (%) or value Total cases 55 (100.00%) Male 35 (63.64%) Female 20 (36.36%) Age <30 years 7 (12.73%) Age 30–39 years 14 (25.45%) Age 40–54 years 22 (40.00%) Age ≥55 years 12 (21.82%) Age, mean ± SD, years 46.2 ± 13.1 Cervical mass 42 (76.36%) Nasal symptoms 27 (49.09%) Ear or hearing symptoms 18 (32.73%) Headache 11 (20.00%) Cervical nodal involvement 41 (74.55%) Stage IVA is the largest single category, and stages III–IVB together account for 42 of 55 cases (76.36%); these stage assignments are illustrative and do not derive from patient imaging. Table 2. Stage distribution AJCC eighth edition stage n (%) I 4 (7.27%) II 9 (16.36%) III 16 (29.09%) IVA 22 (40.00%) IVB 4 (7.27%) The initial diagnosis is established on nasopharyngeal biopsy in 43 cases (78.18%) and on a cervical node specimen in 12 (21.82%). Non-keratinizing undifferentiated carcinoma accounts for 35 cases (63.64%), differentiated non-keratinizing carcinoma for 14 (25.45%), and keratinizing squamous cell carcinoma for six (10.91%). Prominent lymphoid stroma is recorded in 40 (72.73%), necrosis in 16 (29.09%), surface ulceration in 20 (36.36%), and appreciable crush artifact in nine (16.36%). These overlapping microscopic findings are not exclusive categories. Overt keratinization is recorded in all six keratinizing carcinomas and none of the 49 non-keratinizing tumors in this illustrative model. Table 3. Illustrative specimen type and pathological features Feature n (%) Initial nasopharyngeal biopsy 43 (78.18%) Initial cervical node biopsy 12 (21.82%) Non-keratinizing undifferentiated 35 (63.64%) Non-keratinizing differentiated 14 (25.45%) Keratinizing squamous cell carcinoma 6 (10.91%) Prominent lymphoid stroma 40 (72.73%) Tumor necrosis 16 (29.09%) Surface ulceration 20 (36.36%) Crush artifact 9 (16.36%) Overt keratinization 6 (10.91%) Pancytokeratin is positive in all 45 tested tumors (100.00%). CK5/6 is positive in 37/42 (88.10%), p40 in 31/40 (77.50%), and p63 in 39/41 (95.12%). CD45 is negative in the malignant cells of all 15 cases tested; background reactive lymphocytes constitute an internal positive control. Tumor-cell EBER is detected in 43/50 tested specimens (86.00%), including 33/34 undifferentiated (97.06%), 10/12 differentiated (83.33%), and 0/4 keratinizing tumors (0.00%). Five cases lack an EBER assay. The tested denominator is used throughout. Table 4 reports each ancillary stain against its own tested denominator. The modeled tumors retain epithelial-marker expression, while CD45 is absent from tested malignant cells; tumor-cell EBER is positive in 43 of 50 tested specimens. Untested cases are displayed separately and are not treated as negative. Table 4. Illustrative ancillary test findings Marker Positive / tested, n (%) Relevant negative / untested Pancytokeratin 45/45 (100.00%) 10 untested CK5/6 37/42 (88.10%) 5 negative; 13 untested p40 31/40 (77.50%) 9 negative; 15 untested p63 39/41 (95.12%) 2 negative; 14 untested CD45 in tumor cells 0/15 (0.00%) 15 negative; 40 untested Tumor-cell EBER 43/50 (86.00%) 7 negative; 5 untested Table 5 compares EBER status and nodal involvement across the three modeled histological subtypes. EBER positivity and documented nodal disease are most frequent in the undifferentiated group; the keratinizing subgroup is too small for a stable comparative inference. Table 5. Illustrative subtype associations WHO histological subtype Cases n (%) EBER positive / tested Nodal disease n (%) Non-keratinizing undifferentiated 35 (63.64%) 33/34 (97.06%) 29/35 (82.86%) Non-keratinizing differentiated 14 (25.45%) 10/12 (83.33%) 10/14 (71.43%) Keratinizing squamous cell 6 (10.91%) 0/4 (0.00%) 2/6 (33.33%) Total 55 (100.00%) 43/50 (86.00%) 41/55 (74.55%) Table 6 indicates that nasopharyngeal biopsy is the initial diagnostic specimen in each subtype, although cervical node sampling also contributes to diagnosis. Percentages within each subtype use that subtype’s number of cases as the denominator. Table 6. Illustrative initial diagnostic specimen by subtype Histological subtype Nasopharyngeal biopsy n (%) Cervical node biopsy n (%) Undifferentiated 28/35 (80.00%) 7/35 (20.00%) Differentiated 11/14 (78.57%) 3/14 (21.43%) Keratinizing 4/6 (66.67%) 2/6 (33.33%) Total 43/55 (78.18%) 12/55 (21.82%) Table 7 shows the strong concentration of prominent lymphoid stroma in the modeled undifferentiated cases. Necrosis and surface ulceration appear across subtypes, while crush artifact is relevant to interpretation of a limited biopsy. The features are assessed independently and their columns do not sum to 100%. Table 7. Illustrative selected microscopic findings by subtype Histological subtype Lymphoid stroma Necrosis Ulceration Crush artifact Undifferentiated n=35 32 (91.43%) 10 (28.57%) 12 (34.29%) 7 (20.00%) Differentiated n=14 8 (57.14%) 4 (28.57%) 5 (35.71%) 2 (14.29%) Keratinizing n=6 0 (0.00%) 2 (33.33%) 3 (50.00%) 0 (0.00%) Total n=55 40 (72.73%) 16 (29.09%) 20 (36.36%) 9 (16.36%) Table 8 places the modeled WHO subtypes alongside clinical stage. Stage IVA is commonest in the undifferentiated column, but the table is descriptive: the small keratinizing subgroup and simulated stage assignments do not justify a prognostic or causal conclusion. Table 8. Illustrative clinical stage by histological subtype AJCC stage Undifferentiated n=35 Differentiated n=14 Keratinizing n=6 Total n=55 I 2 (5.71%) 2 (14.29%) 0 (0.00%) 4 (7.27%) II 4 (11.43%) 3 (21.43%) 2 (33.33%) 9 (16.36%) III 11 (31.43%) 4 (28.57%) 1 (16.67%) 16 (29.09%) IVA 16 (45.71%) 4 (28.57%) 2 (33.33%) 22 (40.00%) IVB 2 (5.71%) 1 (7.14%) 1 (16.67%) 4 (7.27%) Figure 1 visualizes the unequal subtype frequencies and makes the predominance of the undifferentiated category easier to see. The bar labels show both the modeled count and its percentage of all 55 cases.

In the studied cases, the dominant phenotype is non-keratinizing undifferentiated carcinoma, with 35 of 55 tumors. This is consistent with the prominence of non-keratinizing histology in major pathological accounts, but the modeled proportion cannot be interpreted as the distribution in Mosul [5,10–13]. A real result would depend on which departments supplied cases, referral pathways, the availability of original slides, and whether challenging biopsies underwent expert review. The paper should therefore identify its catchment and selection process before interpreting subtype frequencies. The distinction between non-keratinizing differentiated and undifferentiated morphology can be difficult on small fragments. Syncytial growth, prominent nucleoli, and lymphocytes permeating epithelial nests may favor an undifferentiated pattern, whereas clearer squamous maturation without overt keratinization may support a differentiated pattern. Crush artifact in nine modeled specimens illustrates why the diagnostic confidence must be recorded. A genuine study should preserve an unclassified category when tissue quantity or preservation prevents a reliable distinction. Reclassifying every case into a neat subtype would create false precision [5,17]. A cervical mass is the commonest modeled presentation, and 12 of the 55 initial diagnostic specimens are cervical node biopsies. These observations would make pathological examination relevant to the route of diagnosis, not merely to the final label. In an affected node, epithelial cells may be dispersed among numerous reactive lymphocytes and could be mistaken for a hematolymphoid malignancy. Broad-spectrum cytokeratin can reveal the epithelial component; CD45 helps assess a lymphoid differential. However, cytokeratin positivity establishes epithelial differentiation, not the anatomical origin of the tumor. Clinical examination and imaging must substantiate the nasopharyngeal site, especially when only a node was sampled [6–9]. The modeled p40, p63, and CK5/6 frequencies are presented with different denominators because ancillary stains are selected for specific diagnostic questions. The 77.50% p40 positivity, for example, applies to 40 tested specimens and should never be rendered as 31 of all 55 tumors without explaining the 15 untested cases. Marker sensitivity is also affected by fixation, section quality, scant tumor, and the chosen staining threshold. An immunohistochemical panel should be interpreted against the hematoxylin and eosin appearances and suitable controls. Its numerical distribution in a retrospective series partly reflects the pathologists’ decisions about which cases required staining [5–8]. EBER is the most informative modeled viral result, with tumor-cell positivity in 43 of 50 tested cases. The apparent concentration of positive results in non-keratinizing tumors accords with several investigations, while studies in lower-incidence populations document different mixtures of EBV-associated, HPV-associated, and virus-negative tumors [10–15]. Nevertheless, the keratinizing category contains only four tested cases. The modeled 0/4 result is a description of those specimens, not evidence that all keratinizing tumors in Mosul lack EBV. A negative or indeterminate EBER result would warrant review of tumor representation, assay controls, the histological diagnosis, and the clinical primary site. Signal restricted to background lymphocytes must not be scored as tumor positivity. Viral interpretation requires restraint beyond the EBER result. A patient can have tissue EBER testing, plasma EBV DNA testing, both, or neither; a positive blood test cannot be substituted for localization of the virus within malignant cells. The significance of p16 immunoreactivity in the nasopharynx also differs from its established use as a surrogate in the oropharynx. HPV-specific testing and accurate assignment of primary site are needed before labeling a tumor HPV-driven [14–16]. These distinctions matter because a pathology manuscript is often used later as evidence about a region’s viral epidemiology. The modeled clinical stage distribution contains 42 patients in stage III or IV categories, and cervical nodal involvement appears in 41 patients. Those numbers are included to show how morphology can be read alongside clinical extent, yet pathological specimens cannot establish the full T and M categories on their own. A real paper should specify the staging edition, document the imaging used, and avoid imputing missing stage from the presence of a neck node. With only six keratinizing tumors, comparisons of subtype with nodal disease or stage are particularly vulnerable to chance and confounding. We therefore do not attach P values to these illustrative cross-tabulations. Studies of PD-L1, lymphocytic infiltration, genomic alterations, and epigenetic changes demonstrate the breadth of NPC biology [18–27]. They should enrich the discussion without implying that these markers were measured in the local specimens. Similarly, the treatment guidelines cited here explain why stage and disease extent matter, but this pathology-focused dataset cannot estimate treatment effectiveness or survival [28–30]. Adding response percentages without defined assessment times and complete follow-up would weaken the manuscript rather than strengthen it.

This manuscript demonstrates a complete structure for a 55-case Mosul NPC histopathology study, including detailed morphology, immunohistochemistry, EBER status, clinical presentation, stage, tables, and figures. Every result is illustrative. A publication-ready original article requires verification of the 55 patients, independent review of archived slides, test reports, clinical staging records, and ethics documentation.

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