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Glandular odontogenic cyst (GOC) is a very rare jaw cyst accounting for 0.2% of all odontogenic cysts. It presents usually in adults with a slight male predominance. It shows radiological, histopathological and even immunohistochemical overlap with low grade intraosseous mucoepidermoid carcinoma (MEC) but their distinction is crucial. A 57-year-old woman with bilocular radiolucency in the anterior mandible crossing the midline is described here. Microscopy features were consistent with glandular odontogenic cyst but multiple MEC-like islands were seen in the capsule, creating a diagnostic head trip with low grade intraosseous MEC. However, the absence of cellular atypia and epidermoid and intermediate cells led to a final diagnosis of GOC, with close follow-up of the patient recommended. This rare finding shows the relation between GOC and MEC or the origin of MEC from GOC.

AimsAn increasing number of small pulmonary nodules are being screened by CT, and an intraoperative diagnosis is necessary for preventing excessive treatment. However, there is limited literature on the frozen diagnosis of small sclerosing pneumocytomas (SPs). In particular, tumours smaller than 1 cm are challenging for pathologists performing intraoperative frozen diagnosis.MethodsIn total, 230 cases of SP were surgically resected between January 2015 and March 2019 at Shanghai Chest Hospital, and of them, 76 cases were smaller than 1 cm. The histology and clinical information of these 76 cases (33.0%, 76/230) were reviewed retrospectively, 54 cases of which were diagnosed intraoperatively, and the pitfalls were summarised. All diagnoses were confirmed on permanent sections and immunohistochemical sections.ResultsHistologically, 78.9% (60/76) of the small SP was dominated by one growth pattern, and solid and papillary growth pattern were the most commonly misdiagnosed circumstances. The rate of intraoperative misdiagnosis of these SP smaller than 1 cm was 11.1% (6/54).ConclusionsThe main reason for misdiagnosis was failure to recognise the dual cell populations and the cellular atypia. Diagnostic clues include the gross morphology, the presence of dual-cell populations and a hypercellular papillary core, foam cell accumulation in glandular spaces and haemorrhage and haemosiderin on the periphery. In spite of awareness of pitfalls some cases may still be essentially impossible to diagnose on frozen section.

El nevo de Spitz es una lesión melanocítica benigna poco común, compuesta de células epitelioides y/o fusiformes grandes, que usualmente se presenta en la infancia. Clínicamente son lesiones pequeñas, generalmente de menos de 6 mm de diámetro, con características histológicas benignas (arquitectura regular, escasas o nulas mitosis y ausencia de atipia celular). El patrón en estallido de estrella y el patrón vascular punteado son los patrones dermatoscópicos más frecuentes. El manejo puede ser expectante o excisional dependiendo de las características clínicas y la edad del paciente.

Introduction: Human papillomavirus (HPV) infection remains the most common cause of cervical intraepithelial neoplasia. The objective of this study is to evaluate the sensitivity and predictive value of the HPV test associated with the cervico-uterine smear in the screening of cervical intraepithelial neoplasia in our environment. Methodology: This is a descriptive cross-sectional study of 625 women who consulted in the department of gynecology for cervical cancer screening, of whom 300 received an HPV test; during the period from January the 1st to December 31st, 2018 at Panzi general reference hospital (South-Kivu, DRC). Data analysis was done using Epi Info version 7 software. Results: For all respondents (n = 625), the cervico-uterine smear was normal in 82.88%, inflammatory in 2.4% of cases and with cellular atypia in 14.72%. The HPV test was positive in 87 respondents against 213 negatives cases, i.e. a prevalence of HPV of 29% [95% CI: 23.9% - 34.5%]. Among women with precancerous lesions, 27.6% had HPV infection; among those with normal smears, 29.3% of them had HPV infection; however, this difference was not statistically significant. Patients with dysplastic lesions, 31.3% had genotypes with very high carcinogenic potential; and for those with a normal Pap smear, 45.1% had genotypes with very high carcinogenic potential; however, this difference was also not statistically significant. Conclusion: The human papillomavirus test remains a very important indication cation in the detection of cervical intraepithelial neoplasia, its sensitivity remaining clearly superior to that of cytology, especially for high grade lesions.

To evaluate the role of toluidine blue (TB) staining patterns in diagnosis of ocular surface squamous neoplasia (OSSN) in comparison to that of impression cytology.TB 1% dye was applied to different ocular surface lesions, followed by impression cytology (IC). Dye distribution, intensity, and pattern of uptake by the lesion were scored and total score ≥5 was considered "positive TB staining". The TB results were then compared with those using IC to determine the presence of cellular atypia.The study enrolled 88 eyes of 82 patients. IC demonstrated cellular atypia in 50 (56.8%) cases. Forty-three of 45 "TB-positive" eyes (95.51%) had cellular atypia on IC (p 0.001). Sensitivity and specificity of TB in identifying OSSN were 86% and 94.74%, respectively, with positive and negative predictive values of 95.56% and 83.72%. TB staining intensity of dark blue and/or mixed types and stippled pattern of TB staining were strongly correlated with dysplastic changes in IC (P ˂ 0.001). TB staining distribution whether in form of diffuse, patchy or scattered eyes with atypia did not significantly differ from those without atypia in IC (P = 0.172).The sensitivity and specificity of TB vital dye in diagnosing OSSN can be increased by focusing on color intensity and a stippled pattern.

Granular cell tumours (GCTs) are generally benign neoplasms, which are believed to be of neural origin. They are uncommon in the gastrointestinal tract. They are rarely found in the colon and even more rarely found to be multiple. We present a case of a man who underwent a right hemicolectomy for a submucosal lesion and polyps and was found to have multiple nodules diagnosed as caecal GCTs with cellular atypia. While uncommon, this case shows it remains an important differential due to implications for patient management, given the often benign nature of disease.

Objective: To highlight the most frequent localization of ovarian endometriosis, the presence of atypical endometriosis, and recurrences. Retrospective review of 259 patients diagnosed with ovarian endometriosis treated at Tîrgu-Mures Emergency County Hospital, Obstetric Gynecology Clinic, between January 2014 and December 2018. Methods: Data were collected and analyzed for demographics, size of ovarian endometriotic cyst, and recurrences. Results: Out of 259 patients, 51 patients presented atypia, 20 on the right, 24 on the left, and seven patients were diagnosed with endometriosis with bilateral atypia. Higher susceptibility for left localization was noted. Thirty-nine patients (15.1%) presented recurrence. A statistically significant correlation (p = 0.006) was noted between patients with recurrence and atypia compared with those without atypia and endometriotic cysts larger than 7 cm. Patients with relapse under the age of 40 were noted to have mainly atypia with localization on the right (p = 0.025, OD = 4.107). Conclusion: The presence of endometrioma was not statistically significant correlated with left or right sided localization, recurrent endometriomas larger than 7 cm represents a risk for atypical endometriosis development. Recurrence and atypia appear more often in patients under the age of 40 and are right-sided. The total removal of the endometriomas can prevent the recurrence and subsequently the appearance of atypia and secondary neoplastic conditions.

Dedifferentiated chondrosarcoma is a well-recognized entity, but its occurrence in the distal extremities is exceedingly rare. We present the case of a 49-year-old woman who experienced local recurrence of an “enchondroma” of the proximal phalanx of the fourth finger of the left hand, which had been initially treated with intralesional curettage at another hospital 4 years before, and 1 year before for a local recurrence. The imaging findings indicated an aggressive behavior, and an incisional biopsy showed a highly cellular proliferation of spindle and pleomorphic elements without evidence of matrix production intermixed with few fragments of a well-differentiated cartilaginous neoplasm with bland cellular atypia, focal nuclear hyperchromatism, and binucleation. An isocitrate dehydrogenase 2 R172S mutation was detected. The final diagnosis was dedifferentiated chondrosarcoma. Despite amputation of the fourth finger, the patient developed lung metastases and further local relapse. Recurrent cartilaginous tumors of the extremities should not be underestimated and should be followed in view of the possible acquisition of aggressive clinical behavior.

International audience; Spitz nevi are indolent melanocytic tumors arising preferentially during and after childhood. Over the last decades, recurrent oncogenic drivers, sparsely detected in melanoma, were identified in Spitz melanocytic proliferations. Therefore, the detection of such drivers appears as a relevant diagnostic tool to distinguish both entities. Interestingly, morphologic features might correlate with the oncogenic drivers. Thus, the goal of this study was to assess the performances of previously identified morphological criteria to predict the presence of specific drivers. In total, 352 Spitz melanocytic proliferations either with a genetically identified oncogenic driver or investigated for ALK, ROS1, and NTRK1 overexpression by immunohistochemistry were enrolled in the present study. The microscopic features of the cases were assessed blindly with regards to the molecular status and, performances of previously described morphological criteria to predict the molecular status were assessed applying the likelihood-ratio test (LHR). Overall, an oncogenic driver was identified in 76% of the cases (n = 268/352). No microscopic features allowed the reliable prediction of ROS1- and NTRK1-overexpressing cases. By contrast, a plexiform pattern can contribute to the recognition of ALK-overexpressing cases (LHR(+) = 6.14). Importantly, the pseudo-schwannoma variant was highly suggestive of NTRK3-rearranged cases (LHR(+) = 43). Moreover, atypical/malignant tumor (LHR(+) = 5.18), severe cellular atypia (LHR(+) = 5.07), and p16 loss (LHR(+) = 14) contribute to the recognition of MAP3K8-rearranged cases, while the presence of a sheet-like architecture (LHR(+) = 5.39) and a marked fibrosis of the stroma (LHR(+)=5.06) were predictive of BRAF-fused tumors. To conclude, our study confirms ALK-overexpressing, NTRK3-, MAP3K8-, and BRAF-rearranged cases harbored distinct morphologic features allowing their microscopic recognition.

Background “Atypical cells” parameter in automated urinalysis has recently been introduced. An instrument capable of measuring quantitative and qualitative features of nuclear and cytoplasmic properties of a cell has the potential to detect cellular atypia. Instruments using flow cytometry have been detecting atypical cells in blood for a long time; yet instruments using the same methodology very lately developed this parameter in urinalysis. Materials and methods Samples with an atypical cells value higher than 1 atypical cell/µL were included in the study. Besides automated urinalysis, every sample was reflexed to modular unit for digital imaging. The remainder of each sample was stained with Sternheimer dye and examined manually under a light microscope. Results 50 samples with higher than1 atypical cell/µL result were included in the study. Patients were composed of 43 females (86 %) and 7 males (14 %). The mean age was 47.12 ± 19.45 years. The median atypical cells value was 1.8/µL (95 % range 1.5–2.4/µL). Manual microscopic evaluation of the 50 samples showed atypical cells in 1 sample. The patient had papillary lesions on cystoscopy and pathology report informed a high grade urothelial carcinoma. Other 49 samples were negative for atypical cells in manual microscopy. They were crowded samples with leucocytes and squamous epithelial cells. Conclusions The positive case provided evidence for Sysmex UN’s capability to detect atypical cells in urine. The negative cases presented clues that probable vulvovaginal contamination and crowded specimens could be deceptive for Sysmex UN in this particular parameter.

Lymphocyte-rich effusions of the body cavities may represent a reactive/benign condition, primary effusion lymphoma, or systemic lymphoma with secondary malignant effusion, either as initial presentation or as a late complication. Cytomorphologic examination is essential and fundamental for diagnosis and may provide important clues to the nature of diseases. However, based on morphology alone, cytologic diagnosis of lymphocyte-rich effusions could be very challenging, particularly when the lymphocytes are small. Cytologists/cytopathologists might be uncertain when a lymphocyte-rich effusion specimen warrants a comprehensive hematopathologic workup. Herein we present a simple and practical algorithmic approach. On the basis of the cytomorphology of lymphocytes (small vs. large cells), presence or absence of cellular atypia, and clinical information (an earlier history or current lymphoma), the lymphocyte-rich effusion samples could be triaged for ancillary studies including immunophenotyping and molecular assays if indicated. Incorporation of cytomorphology, correlation with clinical information, and appropriate application of various ancillary techniques is mandatory for a correct diagnosis of lymphocyte-rich effusion specimens.

Early diagnosis of the rare and life-threatening uterine leiomyosarcoma (LMS) is essential for prompt treatment, to improve survival. Preoperative distinction of LMS from benign leiomyoma remains a challenge, and thus LMS is often diagnosed post-operatively. This retrospective observational study evaluated the predictive diagnostic utility of 32 preoperative variables in 190 women who underwent a hysterectomy, with a postoperative diagnosis of leiomyoma (n = 159) or LMS (n = 31), at the Liverpool Women&rsquo, s National Health Service (NHS) Foundation Trust, between 2010 and 2019. A total of 7 preoperative variables were associated with increased odds of LMS, including postmenopausal status (p &lt, 0.001, OR 3.08), symptoms of pressure (p = 0.002, OR 2.7), postmenopausal bleeding (p = 0.001, OR 5.01), neutrophil count &ge, 7.5 &times, 109/L (p &lt, 0.001, OR 5.72), haemoglobin level &lt, 118 g/L (p = 0.037, OR 2.22), endometrial biopsy results of cellular atypia or neoplasia (p = 0.001, OR 9.6), and a mass size of &ge, 10 cm on radiological imaging (p &lt, 0.0001, OR 8.52). This study has identified readily available and easily identifiable preoperative clinical variables that can be implemented into clinical practice to discern those with high risk of LMS, for further specialist investigations in women presenting with symptoms of leiomyoma.

Pacinian neurofibroma (PN), a rare benign dermal tumor characterized by proliferation of pacinian corpuscles in the dermal myxoid stroma. A 50 year female presented with slow growing, soft, painless swelling over right wrist. No other significant history was found. Histopathology revealed proliferation of fibrous connective tissue along with whorled structures. No cellular atypia was found. Immunohistochemistry examination with antibodies against protein S-100 showed diffuse positivity. A diagnosis of Pacinian neurofibroma was made.

Oral mucosal melanoma (OMM) is notorious for having a poor prognosis. Recognition of the early features of OMM by both clinicians and pathologists can play an important role in improving survival. Therefore, the purpose of this report is to increase awareness of the early features of OMM, by presenting 2 cases with longitudinal clinical and histopathologic documentation showing progression of OMM from a deceptively bland premalignant (noninvasive) oral melanocytic lesion (POML). By analyzing the clinical and histopathologic features of POML in our cases, and those in the literature, we found that the concerning features are (1) clinically, a pigmented lesion violating the ABCDE criteria or showing multiple recurrences; and (2) histologically, a melanocytic proliferation, in either a lentiginous or pagetoid pattern with or without cellular atypia. Making a diagnosis of POML prospectively is often challenging. Increasing awareness of the clinical and histopathologic features and complete surgical excision of POML are emphasized.

Canine hemangiosarcoma (HSA) is one of the most common mesenchymal tumors in dogs. Its high metastatic and growth rates are usually associated with poor prognosis. Neoplastic cells of HSA can show various levels of cellular atypia in the same mass and may consist of various populations at different differentiated stages. Up to present, however, there is no report analyzing their differentiation states by comparing cellular atypia with differentiation-related protein expressions. To evaluate whether cellular atypia can be used as a differentiation marker in HSA, we analyzed correlation between cellular atypia and intensities of CD31 and von Willebrand Factor (vWF) staining in HSA cases. We also compared cellular atypia and expression levels of CD31 and vWF in each growth patterns. Our results show that cellular atypia was negatively correlated to CD31 and vWF expression levels but no significant correlation was found between growth patterns and cellular atypia or CD31 and vWF expression levels. Our study suggests that cellular atypia is useful for identifying differentiation levels in HSA cases. This study also provides useful information to determine differentiation levels of cell populations within HSA based only on morphological analysis, which will aid further HSA research such as identifying undifferentiation markers of endothelial cells or finding undifferentiated cell population in tissue sections.

Subependymomas are slowly growing glial tumors, corresponding to WHO grade I. Few descriptions of the cytologic features of this neoplasm are available. This study describes the cytologic features of three subependymomas, as well as their differential diagnosis based on cytology. Three men, aged 52, 56, and 63 years, presented with headache. Magnetic resonance imaging revealed a nodular intraventricular mass in all three patients. Intraoperative squash cytology specimens from the three intraventricular tumors showed nodular clusters with microcystic changes. Nuclei were round to oval in shape, but showed no evidence of severe nuclear atypia or mitoses. Histological examination showed features of subependymoma. Squash cytology findings, including nodular clusters, mild cellular atypia, microcystic changes, and mucoid material, are useful in the rapid intraoperative diagnosis of subependymoma.

The use of lasers to treat melanocytic nevi has been subject to debate because of concerns about their possible malignant transformation (Stratigos et al. 2000; Sardana 2013). In the last few years, it has become relatively clear that laser irradiation is unlikely to increase malignant potential. To date, surgical excision is the standard approach in the removal of these lesions since it allows a histopathologic examination and then the exclusion of cellular atypia. However, the presence of some melanocytic nevi in positions sensitive from the aesthetic or functional point of view, in which surgical removal is difficult to obtain or which will probably leave a noticeable scar, may limit this procedure. Therefore, in these cases laser treatment is preferably applied. To date, different types of laser for melanocytic nevi have been proposed with variable clinical outcomes (Bray et al. 2016; Arora et al. 2015; Hammes et al. 2008; Ohmaru et al. 2011; Zeng et al. 2016).

Parosteal osteosarcoma is a rare, slow-growing tumor most commonly arising from the surface of long bones. Tissue or histological sections from 5 dogs and 1 cat with zygomatic arch masses were examined. Clinical presentations varied from chronic sneezing to facial swelling. Imaging consistently demonstrated osseous proliferation in the area of the zygomatic arch. Histologically, the masses were characterized by well-differentiated fibro-osseous and chondroid components that radiated outward from the periosteum of the zygomatic bone. Cellular atypia and mitotic figures were uncommon. Parosteal osteosarcomas have previously been reported in the skulls of dogs and cats, but only 1 has been reported on the zygomatic arch. Initially, these tumors are of low histologic low grade, but with time, they can show more aggressive behavior and invade the underlying bone.

Objective: Cytopathologic interpretation in Graves disease (GD) is considered challenging due to significant cellular atypia. Study Design: We retrospectively identified 55 fine needle aspirations (FNAs) from 43 patients with GD that subsequently underwent thyroidectomy from 1995 to 2016. Results: There were 5 patients with papillary thyroid carcinoma (PTC) and 4 with follicular adenoma (FA). Of the 5 patients with PTC, FNA was interpreted as PTC in 3, atypia of undetermined significance (AUS) in 1, and adenomatoid nodule (AN) in 1 (with a 0.5-cm incidental microcarcinoma). Of the 4 patients with FA, FNA was interpreted as follicular neoplasm (FN) in 2, AUS in 1, and AN in 1. Of the 46 nonneoplastic nodules, FNA was interpreted as nondiagnostic in 2, benign in 26, AUS in 15, FN in 1, and suspicious for PTC in 2. None was diagnosed as malignant. The sensitivity, specificity, positive predictive value, and negative predictive value of PTC diagnosis in FNA were 60, 100, 100, and 96.2%, respectively. Conclusion: FNA is a useful tool for identifying neoplastic nodules arising in GD. However, cytologic atypia often leads to indeterminate diagnoses (18/46, 39.1%). Awareness of clinical information regarding prior treatment for GD may be helpful to avoid overinterpretation.

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

PurposePhyllodes tumors (PTs) are biphasic tumors accounting for 0.3-1.5% of all breast tumors. Epithelial membrane proteins (EMPs) have been reported in various malignant tumors but their expression in PTs is unclear. In this study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in breast phyllodes tumors (PTs), and to investigate their clinical implications.MethodsIn total, 185 PTs were used for constructing a tissue microarray. Immunohistochemical staining for EMP1, EMP2, and EMP3 was performed, and the results were analyzed along with the clinicopathologic parameters.ResultsIn total, 185 PTs were included in this study, and comprised 138 benign, 32 borderline, and 15 malignant PTs. In malignant PTs, the epithelial component showed decreased expression of EMP1 (P = 0.027), EMP2 (P = 0.004), and EMP3 (P = 0.032), compared to the benign and borderline PTs. Conversely, stromal component of borderline and malignant PTs showed higher expression of EMP1 (P = 0.027), EMP2 (P = 0.004), and EMP3 (P = 0.032) compared to benign PTs. Expression of EMP1 and EMP3 correlated positively with stromal cellularity and cellular atypia (P < 0.001). In the univariate analysis, stromal EMP3 was associated with shorter disease-free survival (P < 0.001), and shorter overall survival (P = 0.034).ConclusionThe expression of EMP1, EMP2, and EMP3 is decreased in the epithelial component and is increased in the stromal component of PT with higher histologic grade. Thus, stromal EMP3 expression may serve as an independent prognostic factor in PT.

Highlights • We report a case of MDA arising from clinical LEGH during 5 years of follow-up. • The first sign suggesting MDA was cellular atypia in endocervical cytology, and was followed by an increase in tumor size. • MDA lesion lacked in stromal reaction and MRI failed to detected MDA. • Worsening cytology and lesion enlargement are important signs for malignant change of LEGH during follow-up.

Tzanck smear test is most often used for the diagnosis of erosive–vesiculobullous lesions. When a cytological examination is performed in an erosive–vesiculobullous lesion, firstly, the acantholytic cell should be checked. If acantholytic cell is positive, multinuclear giant cell, dyskeratosis, corps ronds, grains, and cellular atypia should be examined. If there is only acantholytic cell, direct immunofluorescence test on smear should be performed to distinguish Hailey–Hailey’s disease from pemphigus.

Extraventricular neurocytoma (EVN) is an extremely rare tumor of neuroglial origin with a tendency toward ganglionic or glial differentiation. In the 2016 World Health Organization Classification, EVN was classified as a grade II tumor and described as a neoplasm with good outcome. However, the presence of cellular atypia is an important unfavorable prognostic factor. Here, we describe the first case of a patient with a congenital EVN localized in the brainstem. After a sub-total resection, his disease rapidly progressed despite several chemotherapies, including molecular targeting approaches. He died 13 months after diagnosis. In conclusion, we report an atypical case of EVN presenting an extremely aggressive behavior, despite the absence of cellular atypia. The brainstem origin and the age of the patient may have represented two important prognostic factors for our patient.