Using Artificial Intelligence to Identify Tumor Microenvironment Heterogeneity in Non-Small Cell Lung Cancers.

Lung cancer heterogeneity is a major barrier to effective treatments and encompasses not only the malignant epithelial cell phenotypes and genetics but also the diverse tumor-associated cell types. Current techniques used to investigate the tumor microenvironment can be time-consuming, expensive, complicated to interpret, and often involves destruction of the sample. Here we use standard hematoxylin and eosin-stained tumor sections and the HALO AI nuclear phenotyping software to characterize 6 distinct cell types (epithelial, mesenchymal, macrophage, neutrophil, lymphocyte, and plasma cells) in both murine lung cancer models and human lung cancer samples. CD3 immunohistochemistry and lymph node sections were used to validate lymphocyte calls, while F4/80 immunohistochemistry was used for macrophage validation. Consistent with numerous prior studies, we demonstrated that macrophages predominate the adenocarcinomas, whereas neutrophils predominate the squamous cell carcinomas in murine samples. In human samples, we showed a strong negative correlation between neutrophils and lymphocytes as well as between mesenchymal cells and lymphocytes and that higher percentages of mesenchymal cells correlate with poor prognosis. Taken together, we demonstrate the utility of this AI software to identify, quantify, and compare distributions of cell types on standard hematoxylin and eosin-stained slides. Given the simplicity and cost-effectiveness of this technique, it may be widely beneficial for researchers designing new therapies and clinicians working to select favorable treatments for their patients.

Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an N-of-1 clinical trial.

Background: Lymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases. Methods: We examined the genomic landscape of a patient cohort of LMs (n = 30 cases) that underwent comprehensive genomic profiling using a large-panel next-generation sequencing assay. Immunohistochemical analyses were completed in parallel. Results: These LMs had low mutational burden with hotspot PIK3CA mutations (n = 20) and NRAS (n = 5) mutations being most frequent, and mutually exclusive. All LM cases with Kaposi sarcoma-like (kaposiform) histology had NRAS mutations. One index patient presented with subacute abdominal pain and was diagnosed with a large retroperitoneal LM harboring a somatic PIK3CA gain-of-function mutation (H1047R). The patient achieved a rapid and durable radiologic complete response, as defined in RECIST1.1, to the PI3Kα inhibitor alpelisib within the context of a personalized N-of-1 clinical trial (NCT03941782). In translational correlative studies, canonical PI3Kα pathway activation was confirmed by immunohistochemistry and human LM-derived lymphatic endothelial cells carrying an allele with an activating mutation at the same locus were sensitive to alpelisib treatment in vitro, which was demonstrated by a concentration-dependent drop in measurable impedance, an assessment of cell status. Conclusions: Our findings establish that LM patients with conventional or kaposiform histology have distinct, yet targetable, driver mutations. Funding: R.P. and W.A. are supported by awards from the Levy-Longenbaugh Fund. S.G. is supported by awards from the Hugs for Brady Foundation. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of Arizona Cancer Center (CA023074), the University of New Mexico Comprehensive Cancer Center (CA118100), and the Rutgers Cancer Institute of New Jersey (CA072720). B.K.M. was supported by National Science Foundation via Graduate Research Fellowship DGE-1143953. Clinical trial number: NCT03941782.

Cytopathological characteristics of solitary fibrous tumour involving the pancreas by fine needle aspiration: Making an accurate preoperative diagnosis in an uncommon location.

BACKGROUND: Solitary fibrous tumour (SFT) is a unique mesenchymal neoplasm with classic features on histology and is characterised by the NAB2-STAT6 gene fusion. There are rare reports of SFTs with pancreatic involvement and only two cases in the literature reporting its features by preoperative fine needle aspiration (FNA). Herein, we characterise the cytomorphological features of four SFTs involving the pancreas by FNA to establish a preoperative diagnostic approach. METHODS: The anatomic pathology archives of two academic medical centres were searched to identify patients with a pancreatic FNA cytology specimen and a confirmed diagnosis of SFT by surgical resection. The clinical history, pathological diagnosis, cytomorphological findings, and results of immunohistochemistry (IHC) were reviewed. RESULTS: Four SFTs were identified from four patients with a median age of 59 years. The morphological features were variable but most frequently showed a bland spindled-to-epithelioid proliferation in fragments and single cells with small, oval, elongated, and hypochromatic nuclei in a haphazard arrangement with or without dense collagen. One tumour presented with a concurrent metastasis and showed a pure epithelioid component with necrosis and enlarged, hyperchromatic nuclei with conspicuous nucleoli and scattered mitoses. IHC was necessary for all diagnoses which were confirmed by surgical resection. CONCLUSIONS: SFTs with pancreatic involvement are rare, and non-specific features and tumour heterogeneity can pose a diagnostic challenge on FNA; however, IHC can be used to make a definitive diagnosis. As a result, FNA is a simple, safe, cost-effective, and accurate approach that can be used to diagnose SFT in the pancreas.

Innate immune activation by checkpoint inhibition in human patient-derived lung cancer tissues.

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug's action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients' TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients' native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with 13C6-Glc/13C5,15N2-Gln, multiplex immunofluorescence, and digital spatial profiling (DSP) were employed to interrogate metabolic and functional responses to Pembrolizumab and/or WGP. Primary and BM PD-1+ lung cancer OTC responded to Pembrolizumab and Pembrolizumab + WGP treatments, respectively. Pembrolizumab activated innate immune metabolism and functions in primary OTC, which were accompanied by tissue damage. DSP analysis indicated an overall decrease in immunosuppressive macrophages and T cells but revealed microheterogeneity in immune responses and tissue damage. Two TMEs with altered cancer cell properties showed resistance. Pembrolizumab or WGP alone had negligible effects on BM-lung cancer OTC but Pembrolizumab + WGP blocked central metabolism with increased pro-inflammatory effector release and tissue damage. In-depth metabolic analysis and multiplex TME imaging of lung cancer OTC demonstrated overall innate immune activation by Pembrolizumab but heterogeneous responses in the native TME of a patient with primary NSCLC. Metabolic and functional analysis also revealed synergistic action of Pembrolizumab and WGP in OTC of metastatic NSCLC.

Description of a Lung Cancer Hotspot: Disparities in Lung Cancer Histology, Incidence, and Survival in Kentucky and Appalachian Kentucky.

INTRODUCTION: Kentucky is recognized as the state with the highest lung cancer burden for more than 2 decades, but how lung cancer differs in Kentucky relative to other US populations is not fully understood. PATIENTS AND METHODS: We examined lung cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program by Kentucky and the other SEER regions for patients diagnosed between 2012 and 2016. Our analyses included histologic types, incidence rates, stage at diagnosis, and survival in Kentucky and Appalachian Kentucky relative to other SEER regions. RESULTS: We found that both squamous cell carcinomas and small-cell lung cancers represent larger proportions of lung cancer diagnoses in Kentucky and Appalachian Kentucky than they do in the SEER registries. Furthermore, age-adjusted cancer incidence rates were higher in Kentucky for every subtype of lung cancer examined. Most notably, for Appalachian women the rate of small-cell carcinomas was 3.5-fold higher, and for Appalachian men the rate of squamous cell carcinoma was 3.1-fold higher, than the SEER rates. In Kentucky, lung cancers were diagnosed at later stages and lung cancer survival was lower for adenocarcinoma and neuroendocrine carcinomas than in SEER registries. Squamous cell carcinomas and small-cell carcinomas were most lethal in Appalachian Kentucky. CONCLUSION: Together, these data highlight the considerable disparities among lung cancer cases in the United States and demonstrate the continuing high burden and poor survival of lung cancer in Kentucky and Appalachian Kentucky. Strategies to identify and rectify causes of these disparities are discussed.

Association Between Obesity and Histological Tumor Budding in Patients With Nonmetastatic Colon Cancer.

Importance: Obesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown. Objective: To evaluate the association of TB with obesity and other prognostic factors in colon cancer. Design, Setting, and Participants: This cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to III colon cancer; patients with stage 0, stage IV, or incomplete data were excluded. Main Outcomes and Measures: TB was defined as 1 to 4 malignant cells at the invasive edge of the tumor, independently assessed by 2 academic pathologists. The primary outcome was the association of TB with obesity (defined as body mass index [BMI] of 30 or greater). Secondary outcomes include the association of TB with clinical features (ie, age, race, sex, TNM stage, tumor location) and pathological features (ie, poorly differentiated tumor clusters [PDCs], Klintrup-Mäkinen inflammatory score, desmoplasia, infiltrative tumor border, tumor necrosis, and tumor-to-stroma ratio). Results: A total of 200 specimens were reviewed. The median (interquartile range) age of patients was 62 (55-72) years, 102 (51.0%) were women, and the mean (SD) BMI was 28.5 (8.4). A total of 57 specimens (28.5%) were from stage I tumors; 74 (37.0%), stage II; and 69 (34.5%), stage III. Of these, 97 (48.5%) had low-grade (<5 buds), 36 (18.0%) had intermediate-grade (5-9 buds), and 67 (33.5%) had high-grade (≥10 buds) TB. Multivariable analysis adjusting for clinical and histological factors demonstrated that higher TB grade was associated with obesity (odds ratio [OR], 4.25; 95% CI, 1.95-9.26), higher PDC grade (grade 2 vs 1: OR, 9.14; 95% CI, 3.49-23.93; grade 3 vs 1: OR, 5.10; 95% CI, 2.30-11.27), increased infiltrative tumor border (OR, 1.03; 95% CI, 1.01-1.04), cecal location (OR, 2.55; 95% CI, 1.09-5.97), and higher stage (eg, stage III vs stage I for high-grade or intermediate-grade vs low-grade TB: OR, 2.91; 95% CI, 1.00-8.49). Additionally, patients with a higher TB grade had worse overall survival (intermediate vs low TB: hazard ratio, 2.20; 95% CI, 1.11-4.35; log-rank P = .02; high vs low TB: hazard ratio, 2.67; 95% CI, 1.45-4.90; log-rank P < .001). Conclusions and Relevance: In this cohort study, a novel association between high TB grade and obesity was found. The association could reflect a systemic condition (ie, obesity) locally influencing aggressive growth (ie, high TB) in colon cancer.

Myeloid arginase-1 controls excessive inflammation and modulates T cell responses in Pseudomonas aeruginosa pneumonia.

Regulatory properties of macrophages associated with alternative activation serve to limit the exaggerated inflammatory response during pneumonia caused by Pseudomonas aeruginosa infection. Arginase-1 is an important effector of these macrophages believed to play an essential role in decreasing injury and promoting repair. We investigated the role of arginase-1 in the control of inflammatory immune responses to P. aeruginosa pneumonia in mice that exhibit different immunologic phenotypes. C57BL/6 mice with conditional knockout of the arginase-1 (Arg1) gene from myeloid cells (Arg1ΔM) or BALB/c mice treated with small molecule inhibitors of arginase were infected intratracheally with P. aeruginosa. Weight loss, mortality, bacterial clearance, and lung injury were assessed and compared, as were the characterization of immune cell populations over time post-infection. Myeloid arginase-1 deletion resulted in greater morbidity along with more severe inflammatory responses compared to littermate control mice. Arg1ΔM mice had greater numbers of neutrophils, macrophages, and lymphocytes in their airways and lymph nodes compared to littermate controls. Additionally, Arg1ΔM mice recovered from inflammatory lung injury at a significantly slower rate. Conversely, treatment of BALB/c mice with the arginase inhibitor S-(2-boronoethyl)-l-cysteine hydrochloride (BEC) did not change morbidity as defined by weight loss, but mice at day 10 post-infection treated with BEC had gained significantly more weight back than controls. Neutrophil and macrophage infiltration were similar between groups in the lung parenchyma, and neutrophil migration into the airways was reduced by BEC treatment. Differences seem to lie in the impact on T cell subset disposition. Arg1ΔM mice had increased total CD4+ T cell expansion in the lymph nodes, and increased T cell activation, IFNγ production, and IL-17 production in the lymph nodes, lung interstitium, and airways, while treatment with BEC had no impact on T cell activation or IL-17 production, but reduced the number of T cells producing IFNγ in the lungs. Lung injury scores were increased in the Arg1ΔM mice, but no differences were observed in the mice treated with pharmacologic arginase inhibitors. Overall, myeloid arginase production was demonstrated to be essential for control of damaging inflammatory responses associated with P. aeruginosa pneumonia in C57BL/6 mice, in contrast to a protective effect in the Th2-dominant BALB/c mice when arginase activity is globally inhibited.

Evaluation of Diagnostic Utility of a High-Risk Human Papillomavirus PCR Test on Formalin-Fixed, Paraffin-Embedded Head and Neck Tumor Tissues.

The increasing prevalence of high-risk human papillomavirus (HR-HPV)-associated head and neck squamous cell carcinoma (HNSCC) has prompted strong clinical demands for detecting HR-HPV directly in the tumor. Although p16 immunohistochemistry (IHC) has been the standard testing method, it has limitations including false positivity, lack of sensitivity in low tumor cell samples such as fine-needle aspirate (FNA), and its subjectivity. We developed a modified method based on a commercial automated HR-HPV PCR assay and evaluated the performance characteristics and the diagnostic utility of this assay for direct HR-HPV detection in the HNSCC samples. HNSCC formalin-fixed, paraffin-embedded blocks were retrieved from archives including 44 excisions, 63 biopsies, and 16 FNAs. Tissue slices were trimmed from the blocks, deparaffinized, lysed, and loaded on the commercial automated platform for HR-HPV PCR. All specimens had a concurrent p16 IHC performed. The PCR assay showed high concordance with the p16 IHC (96%; 99/103) and excellent positive agreement (91.5%) and negative agreement (100%). In addition, the PCR assay provided more conclusive results in samples with equivocal p16 IHC results. The modified commercial automated HR-HPV PCR test is a labor-efficient, quick, reliable, sensitive, and specific method for detecting HR-HPV in formalin-fixed, paraffin-embedded samples. This assay also showed excellent diagnostic utility in samples with equivocal p16 IHC results, including FNA cell blocks.

Mammary analog secretory carcinoma of thyroid: A case report.

Mammary analog secretory carcinoma (MASC) is a recently described rare neoplasm that was first reported in the salivary gland with an associated ETV6-NTRK3 fusion. We present a case of MASC involving and presumably arising in the thyroid, which was originally diagnosed as papillary thyroid carcinoma on fine needle aspiration and surgical resection. The later correct diagnosis of MASC was confirmed by immunohistochemistry and molecular studies. The cytopathological features of MASC in the salivary gland are previously described; however, we present the first cytopathological description of MASC arising in the thyroid with the unique feature of prominent nuclear grooves. Differentiating MASC from overlapping features of cytopathologic mimics such as papillary thyroid carcinoma may carry crucial therapeutic implications. Diagn. Cytopathol. 2017;45:45-50. © 2016 Wiley Periodicals, Inc.

Tumor MET expression may not predict the risk of venous thromboembolism in cancer patients.

Venous thromboembolism (VTE) occurs at an increased incidence in cancer patients. A cancer-related hypercoagulable state has been considered to play role in this phenomenon. Preclinical data suggest an association between tumor expression of MET proto-oncogene (MET) and a hypercoagulable state, resulting in VTE. We investigated this association in this retrospective study. Thirty-five cancer patients with documented VTE and no relevant predisposing factors were compared with 35 matched cancer patients without VTE who served as controls. Pathology specimens of all patients and controls were stained by immunohistochemistry (IHC) for MET protein. Intensity of reactivity to the MET antibody was read as 0 (negative), 1+ (equivocal), and 2+ (positive). The pathologists were blinded to the patient VTE status. The MET reactivity in tissue sections were compared between the two cohorts. No significant difference was observed between the two groups for MET expression. This study's findings indicate no association between the reactivity for MET protein as measured through an immunohistochemical technique, and the incidence of VTE in cancer patients.

In vivo light scattering for the detection of cancerous and precancerous lesions of the cervix.

A noninvasive optical diagnostic system for detection of cancerous and precancerous lesions of the cervix was evaluated in vivo. The optical system included a fiber-optic probe designed to measure polarized and unpolarized light transport properties of a small volume of tissue. An algorithm for diagnosing tissue based on the optical measurements was developed that used four optical properties, three of which were related to light scattering properties and the fourth of which was related to hemoglobin concentration. A sensitivity of ~77% and specificities in the mid 60% range were obtained for separating high grade squamous intraepithelial lesions and cancer from other pathologies and normal tissue. The use of different cross-validation methods in algorithm development is analyzed, and the relative difficulties of diagnosing certain pathologies are assessed. Furthermore, the robustness of the optical system for use by different doctors and to changes in fiber-optic probe are also assessed, and potential improvements in the optical system are discussed.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering.

OBJECTIVE: To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. MATERIALS AND METHODS: A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. RESULTS: Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. CONCLUSIONS: The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating "see and treat" protocols is a longer term goal. Improvements in accuracy are essential.

In vivo light scattering measurements for detection of precancerous conditions of the cervix.

OBJECTIVE: To examine the utility of in vivo elastic light scattering measurements to diagnose high grade squamous interepithelial lesions (HSIL) of the cervix. METHODS: A newly developed fiber optic probe was used to measure light transport in the cervical epithelium of 36 patients undergoing standard colposcopy. Both unpolarized and polarized light transport were measured in the visible and near-infrared. Spectroscopic results of 29 patients were compared with histopathology of the measured sites using ROC curves, MANOVA and logistic regression. RESULTS: Three spectroscopic parameters are statistically different for HSIL compared with low-grade lesions and normal tissue. When these three spectroscopic parameters are combined, retrospective sensitivities and specificities for HSIL versus non-HSIL are 100% and 80%, respectively. CONCLUSIONS: Reflectance measurements of elastically scattered light show promise as a non-invasive, real-time method to discriminate HSIL from other abnormalities and normal tissue. These results compare favorably with those obtained by fluorescence alone and by fluorescence combined with light scattering.

Collagen and biphasic calcium phosphate bone graft in large osseous defects.

The cavity left by the removal of tumors represents a challenge for the orthopedic oncologic surgeon. This article takes a critical look at the use of a synthetic bone graft to fill the residual space. A combination of hydroxyapatite, tricalcium phosphate, and bovine collagen was used for intramedullary tumors. Thirty patients were followed for an average of 23 months. The majority (93%) returned to full activity with only 6 (20%) complications. Study results showed collagen and biphasic calcium phosphate ceramic bone graft makes an effective substrate for filling intramedullary cavities remaining after tumor excision.

Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers.

The prevalence of methylation of the p16, DAPK and RASSF1A genes was investigated in lung adenocarcinoma from smokers, former uranium miners and never smokers. The association between a common genetic alteration in adenocarcinoma, mutation of the K-ras gene and methylation of these genes, as well as survival was examined. Adenocarcinomas from 157 smokers, 46 never smokers and 34 former uranium miners were evaluated for methylation of the p16, DAPK and RASSF1A genes using the methylation-specific PCR assay. Comparisons were also made to prevalences of methylation of the MGMT gene and mutation of the K-ras gene previously examined in these tumors. The prevalence of methylation for all genes was similar between adenocarcinomas from smokers and never smokers, although the prevalence for methylation of the p16 gene tended to be higher in smokers compared to never smokers. A significantly higher prevalence for p16 methylation was seen in central vs. peripheral lung tumors. At least 1 gene was methylated in 35% of stage I tumors, whereas 2 and >/=3 genes were methylated in 40% and 16% of tumors, respectively. Methylation of all genes was independent of K-ras mutation, whereas methylation of the DAPK and RASSF1A genes was positively associated. Environmental tobacco smoke, the strongest lung cancer risk factor among never smokers, induces adenocarcinoma in part through inactivation of the p16, DAPK and RASSF1A genes. Adenocarcinomas may develop through 2 distinct processes: multiple gene inactivations through promoter hypermethylation and activation of the K-ras gene.

Promoter hypermethylation of the O6-methylguanine-DNA methyltransferase gene: more common in lung adenocarcinomas from never-smokers than smokers and associated with tumor progression.

Adenocarcinoma (AC) is the most common type of lung cancer diagnosed in the United States, comprising up to 40% of tumors in smokers and 50-80% of tumors in never-smokers. Exposures to cigarette smoke, direct or second-hand, and radiation in the form of radon progeny are the major risk factors for lung AC in both smokers and never-smokers. The goal of the current study was to determine the prevalence for O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in a large sample of central or peripheral ACs from smokers (n = 157), former uranium miners (n = 34), and never-smokers (n = 46). The mutation rate at codon 12 of the K-ras gene was determined to assess whether activation of this oncogene was associated with MGMT methylation. The overall prevalence for MGMT methylation was 51%. Significantly more tumors from never-smokers than smokers exhibited MGMT methylation (66 versus 47%, respectively). In contrast, exposure to radon through uranium mining did not affect the prevalence for methylation. The frequency of MGMT methylation was increased significantly in association with tumor stage. K-ras mutations were detected in 24% of all ACs and 22, 24, and 28% of tumors from never-smokers, smokers, and miners, respectively. Alterations in both the K-ras and MGMT genes were seen in only 11% of ACs. Kaplan-Meier survival estimates did not reveal any difference between patient survival with or without MGMT methylation. In contrast, survival was significantly reduced over the initial 60 months after diagnosis for patients with a transition mutation in the K-ras gene compared with those with a transversion mutation. This investigation demonstrates that MGMT promoter hypermethylation is a common event in the progression of early stage AC of the lung. We have shown that the incidence of MGMT methylation was significantly higher in never-smokers than smokers and have detected a higher frequency of mutations within the K-ras gene than previously reported in never-smokers. This study also suggests that K-ras activation is independent of MGMT methylation.

Primary plasmacytoma arising in an endocervical polyp with detection of neoplastic cells on papanicolaou test. A case report and review of the literature.

Primary plasmacytomas of the female genital tract are extremely rare and present a substantial diagnostic challenge. Five cases morphologically representing plasmacytomas and localized to the uterine cervix have been reported previously; however, only 1 was shown to be monotypic for immunoglobulin light-chain expression. We report the case of a 37-year-old woman who had highly atypical plasma cells on her Papanicolaou test. A clinically detected endocervical polyp was removed and revealed a plasmacytoma, the diagnosis of which was substantiated by demonstrating monotypic lambda-light-chain restriction and a clonal immunoglobulin heavy-chain gene rearrangement. The cytologic and histopathologic findings of plasmacytomas of the uterine cervix are discussed, including the utility of immunophenotypic and molecular techniques to confirm the neoplastic diagnosis.