Degree Of Cytologic Atypia Research Articles

Uterine Smooth Muscle Tumors: An Overview.

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa. Recent advances in molecular diagnostics have refined the classification of smooth muscle tumors, but most cases are diagnosed purely on histologic grounds.

High-grade myoepithelial carcinoma of the palate and maxillary sinus complex: a case report

<h3>Introduction</h3> Myoepithelial tumors typically arise from myoepithelial cells of salivary glands, however myoep- ithelial tumors arising in the skin and soft tissues have been increasingly recognized. Myoepithelial carcinomas (MC) have been described in each of these anatomic locations. Myoepithelial carcinoma of the salivary gland is a rare neoplasm composed exclusively of myoepithelial cells. The diagnosis of myoepithelial carcinoma is based on establishing the immunophenotype of the cellular proliferation, degree of cytologic atypia, presence of mitoses and necrosis, and exclusion of mimics. The morphologic heterogeneity further complicates the diagnosis of MC. <h3>Case Findings</h3> A 54-year-old woman presented with a progressive enlargement of the left palate, with imaging demonstrating involvement of adjacent maxillary sinus with extension to the floor of the orbit. Histologically, the lesion was characterized by malignant appearing epithelioid and clear cells compactly arranged in confluent sheets with no evidence of ductal differentiation. The sheets of tumor cells had a somewhat lobular architecture demar- cated by thin vascular septa. Nuclear pleomorphism, numerous mitoses, and focal necrosis were present. <h3>Results</h3> Positive immunohistochemical staining of tumor cells with CK7, SOX10, S100, P63, P40, and SMA favored a myoepithelial phenotype. <i>SMARCB1</i> (<i>INI1</i>) was expressed, excluding <i>SMARCB1</i>-deficient sinonasal carcinoma. Neg- ative staining of tumor cells for TTF1, CD20, GFAP, calponin, HMB45, PAX8, CD31, CD34 appear to exclude melanoma, renal cell carcinoma, renal cell like sinonasal carcinoma, thyroid carcinoma, lung carcinoma and PEComa. Outside consultation reported positive P16 but the tumor was negative for high risk HPV, thus excluding HPV related mul- tiphenotypic sinonasal carcinoma. Ki-67 revealed a high proliferative index of 70%. <h3>Conclusions</h3> This study demonstrates the clinical and histopathologic findings of a high-grade myoepithelial carci- noma involving the palate and maxillary sinus complex. Exclusive myoepithelial differentiation (morphologic and immunophenotypic) accompanied by established criteria of malignancy allow for definitive diagnosis of this rare salivary gland tumor.

Congenital thymoma.

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (<18 years of age), the youngest being 4 years old, and no cases in newborns. They represent less than 1% of all mediastinal tumors in children. Due to the limited number of cases in the pediatric population, the diagnosis and treatment in this population is extremely challenging. Thymomas in all age groups may be associated with paraneoplastic syndromes, being myasthenia gravis the most common, which is associated with a worse prognosis in the pediatric population. We present the first case of a newborn infant with congenital thymoma. This case demonstrates a rare tumor in an unusual age group and emphasizes the importance of multidisciplinary teamwork in the decision-making and management of this condition.

Subungual Keratoacanthoma: A Rare Variant of Keratoacanthoma

Sungungual keratoacanthoma is a rare and more aggressive variant of keratoacanthoma. The authors present a case of a 49-year-old male with a one year history of a growing exophytic nodule on the nail bed of the left first toe. Physical examination revealed a two centimeters large exofitic nodule with a verrucous hyperkeratotic central area on the nail bed. A plain radiograph showed a cup-shaped lytic defect in the underlying distal phalanx. Histopathologic analysis revealed a large crater-like squamoproliferative lesion, connected to the epidermis and consisting of lobules and nests of glassy epithelium with numerous dyskeratotic cells, very little degree of cytological atypia and low mitotic activity. Lymphovascular, perineural or bone invasion were not found. Immunohistochemistry with p53 and Ki67 showed exclusive focal basal staining. The diagnosis of subungual keratoacanthoma was made. The main differential diagnosis, both clinical and histological, is with squamous cell carcinoma. It is important to consider this entity to avoid unnecessary diagnostic delays and mutilating treatments.

Histopathologic correlation of high-risk MelaFindTM lesions: a 3-year experience from a high-risk pigmented lesion clinic.

A significant number of pigmented lesions are biopsied to rule out melanoma, but most will be benign. MelaFindTM is a highly sensitive, noninvasive computer-assisted system to aid in clinical diagnosis of melanoma. A total of 140 high-risk patients were followed by one expert dermatologist. Biopsies were blindly and independently evaluated by two dermatopathologists and given histologic severity scores (HSS, 0-12) based on the histologic features of melanoma/dysplastic nevi and compared to pathologic diagnoses and MelaFindTM scores. MelaFindTM reduced the biopsy number of clinically ambiguous lesions (923 scanned to 253 biopsied, 73% reduction). Biopsied cases were usually benign (135/253, 53.4%, HSS = 2.8-3.2). Dysplastic nevi with varying degrees of atypia were observed next most commonly (80/253, 31.6%, HSS = 4.7-5.2 for mild dysplasia and 7-7.6 for moderate to severe dysplasia). Melanomas comprised 11/253 (4.3%) of biopsies (HSS = 9.3-10.7). Twenty-four cases were given miscellaneous diagnoses not within the dysplastic nevus-melanoma spectrum (9.5%, HSS = 1.3). Dermal fibrosis was the most commonly identified worrisome histologic feature (177/253, 70%), closely followed by other known atypical features. Nonthreatening histologic features in benign lesions with high MelaFindTM disorganization scores were common. The HSS differed significantly depending on pathologic diagnosis severity, while the MelaFindTM score did not (benign = 2.2; mildly atypical = 4.8; moderately to severely atypical = 2.3; in-situ or invasive melanoma = 3.1). MelaFindTM unequivocally reduced the number of biopsies, but banal lesions had histologic attributes resulting in high-risk MelaFindTM scores, and MelaFindTM does not correlate with degree of cytologic atypia. Knowledge of these limitations should increase bidirectional confidence when making clinicopathologic correlations in high-risk patients.

Cytohistological discrepancies of cervico-vaginal smears and HPV status.

Discrepancies between abnormal cervical cytology or high-risk human papillomavirus (HR-HPV) status (cytolo-gy negative/HPV positive) and subsequent histological findings are a common occurrence. After using co-testing, the dis-crepancies between the HR-HPV status and cervical cytology have become an issue. In this study, we aimed to determine the characteristics of women with a discrepancy between histology and cytology/HR-HPV status, in terms of diagnosis, review and identification. A total of 52 women, patients of the University Hospital between 2013-2015, with cytohistologi-cal or HR-HPV status discrepancy were recruited for the study and retrospectively analyzed. The cytological samples were liquid-based Pap smears, classified according to the 2001 Bethesda system. The HR-HPV status was identified using the Hybrid Capture 2 HR-HPV DNA assay. The histological samples were obtained by cervical biopsy as well as large loop exci-sion of the transformation zone (LLETZ). A cytohistological discrepancy was demonstrated in patients with (-)cytology/HR-HPV(+), ASCUS, LSIL, ASC-H, HSIL, AGC-NOS: 17.3%, 23.07%, 26.9%, 9.5%, 17.3% and 5.7%, respectively. When the degree of atypia in cytology increases, the concurrency of cervical cytology with biopsy also increases. A positive HR-HPV co-test result (19/24, 79.1%) was observed in nearly all CIN2 ≥ (+) cases. Our study emphasizes the significance of HR-HPV testing to determine CIN2 ≥ (+) cases, even in the presence of a normal cytological result. In case of cytohistological or HR-HPV discrepancies, a careful review of the HR-HPV status and the degree of cytological atypia should be performed before further intervention.

Squamous cell carcinoma with osteoclast-like giant cells: a morphologically heterologous group including carcinosarcoma and squamous cell carcinoma with stromal changes.

Cutaneous squamous cell carcinoma (SCC) with osteoclast-like giant cells (hereafter, osteoclastic cells) is very rare; eight cases have been reported since 2006. Whether the osteoclastic cells represents a reactive or neoplastic change remains a matter of debate. Osteoclastic cells are often observed in the sarcomatous component of cutaneous carcinosarcoma. SCC with osteoclastic cells is a heterogeneous condition that includes SCC with stromal changes containing osteoclastic cells (also known as osteoclast-like giant cell reaction) and carcinosarcoma. In some cases, SCC with an associated osteoclast-like giant cell reaction has been differentiated from carcinosarcoma based on the degree of cytologic atypia in non-epithelial components. We summarized the clinical and histopathologic characteristics of 11 patients of SCC with osteoclastic cells, including our two cases of SCC with an osteoclast-like giant cell reaction and one case of carcinosarcoma. The affected patients were old and more likely to be male (64%). Seven cases (64%) were in the head and neck. Moreover, multiple features of high risk SCC were observed, such as a tumor size greater than 2 cm (56%), moderate or poor differentiation (100%), recurrence (33%) and nodal metastasis (17%) after excision and immunosuppression (27%). Interestingly, half of the previously reported cases of SCC with osteoclastic giant cell reaction had histopathologic findings that were overlapping with those of carcinosarcoma.

Clear cell carcinoma of the ovary: evaluation of prognostic parameters based on a clinicopathological analysis of 100 cases.

The aim of this study was to evaluate the clinicopathological features of ovarian clear cell carcinomas in order to identify which, if any, are prognostically significant, and to determine whether there is value in grading these tumours. One hundred tumours with clinical follow-up were reviewed. Features evaluated included age, preoperative/intraoperative rupture, size, architectural pattern(s), presence of oxyphilic cells, degree of cytological atypia, nucleolar grade, mitoses, background precursor and stage. Survival differences were analysed using the log-rank test and Kaplan-Meier estimator. Stage and lymph node status were the only parameters that were statistically significant (P < 0.0001). Patients with stage I disease (71%) had a 92% 5-year survival compared to a 31% 5-year survival in advanced stage disease (29%). Those with negative lymph nodes (92%) had an 80% 5-year survival compared to a 22% 5-year survival for those with positive nodes (8%). This study shows that stage and lymph node status are the only prognostically significant parameters in patients with ovarian clear cell carcinoma. It also confirms that most patients with clear cell carcinoma present with disease confined to the ovary, and have an excellent prognosis. Grading ovarian clear cell carcinomas based on morphological features is not recommended, as none are of prognostic significance.

Ovarian Serous Tumors of Low Malignant Potential With Nodal Low-grade Serous Carcinoma

Serous tumor of low malignant potential (SLMP) and low-grade serous carcinoma (LGSC) are part of one biological continuum, whereby SLMP can transform into LGSC. It has been suggested that some nodal SLMPs arise from nodal endosalpingiosis and evolve independently in lymph nodes (rather than being related to the ovarian primary). In this article, we present the clinicopathologic features of 5 cases of nodal LGSC presenting in association with ovarian SLMP. Clinical information was obtained from the patients' charts. Pathologic features of the nodal LGSC, including lymph node location, size of and extent of involvement of tumor, architectural pattern, degree of cytologic atypia, mitotic index, and presence of psammoma bodies, were recorded. Ovarian SLMPs were noted for laterality, size, presence of surface excrescences, microinvasion, and micropapillary/cribriform pattern and for presence of autoimplants, invasive, and noninvasive implants. The distribution of any lymph nodes with nodal endosalpingiosis or SLMPs was also recorded. Patients ranged in age from 28 to 68 years (median, 32 y). In 4 cases, the diagnosis of nodal LGSC occurred at a different time from that of the ovarian SLMPs, ranging from 7 months before to 5 months after the ovarian tumor diagnosis. Nodal LGSC was detected in supraclavicular (2 cases), cervical, intramammary, and periaortic lymph nodes (1 case each). The gross lymph node size ranged from 0.9 to 2.5 cm (median, 1.3 cm). The tumors either replaced the entire lymph node or were found diffusely involving subcapsular and medullary sinuses or lymph node cortices. Tumor cells showed typical cytologic features of LGSC and no mitotic activity. In 2 cases, however, focal pleomorphic cells and 1 mitosis per 10 HPF were noted. Psammoma bodies were identified in all cases. When immunohistochemical analysis was performed, all tumors exhibited a profile in keeping with Müllerian origin. All ovarian tumors were well sampled and ranged in size from 0.1 to 13 cm (median, 2.5 cm). No ovarian SLMP tumors showed the micropapillary/cribriform pattern, whereas only focal microinvasion was detected in 3 cases. Four tumors had surface excrescences. All cases had noninvasive implants, and a single case also had invasive implants. Lymph node dissection was performed in 2 cases, revealing extensive endosalpingiosis in pelvic and periaortic lymph nodes and SLMP in pelvic lymph nodes. In 1 additional case, a single lymph node was sampled, revealing a nodal SLMP. Clinical follow-up ranged from 2 to 14 years (median, 9 y). All patients received postoperative chemotherapy. None of the patients experienced recurrence in pelvic or abdominal soft tissue. Two patients are free of disease. However, 2 patients, one with cervical and another with supraclavicular nodal LGSC, had recurrences at these sites and subsequently succumbed to metastatic disease. Both of these patients had pelvic and periaortic nodal SLMP and extensive nodal endosalpingiosis. Another patient, originally with supraclavicular LGSC, developed pelvic and abdominal lymphadenopathy, and is currently alive with disease. For the first time, we present a case series of patients with ovarian SLMP who, despite any evidence of LGSC in the pelvis or any pelvic recurrences, developed extrapelvic/extra-abdominal nodal LGSC. These patients also had endosalpingiosis and SLMP in pelvic and periaortic lymph nodes, suggesting that SLMP/LGSC tumors in lymph nodes may arise independently of the ovarian primary, progress along their own timeline, and undergo metastatic spread. Therefore, in patients with ovarian SLMP and extensive pelvic/periaortic nodal endosalpingiosis and/or SLMP, examination and follow-up of extrapelvic lymph nodes are warranted, even if the ovarian tumor lacks high-risk features of recurrence.

Gene methylation in random FNA samples as biomarkers for breast cancer.

518 Background: Current methods to determine breast cancer risk are insufficiently sensitive to select women most likely to benefit from preventive strategies. We hypothesized that candidate gene promoter hypermethylation may provide an individualized risk profile. We performed a prospective study to determine whether DNA cumulative methylation index (CMI) varies by menstrual phase or menopausal status, and to correlate CMI with established risk factors. Methods: We obtained random fine needle aspiration (rFNA) samples from healthy women age 35-60 and determined their menopausal and menstrual status, lifetime Gail risk, mammographic breast density, and cytologic atypia assessed as the Masood score. We evaluated CMI of 11 candidate genes in rFNA cells using the Quantitative Multiplex Methylation-Specific PCR (QM-MSP) technique. We used Wilcoxon test and ANOVA model to compare CMI across menopausal and menstrual (follicular, mid-cycle, luteal) categories, respectively. We used linear regression model to adjust for age and BMI. Methylation scores were log-transformed in the analysis. Results: We enrolled 390 women at the Avon Breast Centers at Johns Hopkins and Northwestern, the majority through the Love/Avon Army of Women, and 380 completed study procedures. Median age 50 (36-60), mean BMI 28 (18.7-50.8), 52% were postmenopausal. Mean life-time Gail risk 14.6 (5.6-54.1), mean percent mammographic density 19.6 (2.5-72.8), and mean Masood score (N=354) 13.6 (7-18). QM-MSP analysis was completed on 229 samples. We did not observe differences in CMI among menopausal (P=0.4895) or menstrual categories (P=0.2333). There was no association between CMI and life-time Gail risk (P=0.706) or breast density (P=0.4116). We observed a significant correlation between CMI and Masood score (P=0.0167). Conclusions: CMI correlates with degree of cytologic atypia and is potentially a robust indicator of breast cancer risk since it does not vary with menstrual or menopausal status. Next, we will select genes that best reflect changes in the clinical parameters to create a gene methylation signature that will be validated in other studies and correlated with breast cancer risk.

A case of unclassified multicystic biliary tumor with biliary adenofibroma features

A 40-year-old Japanese man was admitted to our hospital for evaluation of upper abdominal pain. Abdominal computed tomography (CT) revealed a well-circumscribed multicystic mass measuring approximately 7 × 6 cm. The mass contained a solid lesion measuring 3 × 2 cm. Biopsy of a swollen cervical lymph node led to a diagnosis of diffuse large B-cell lymphoma. After initial chemotherapy for lymphoma, the multicystic mass was surgically resected. The tumor was composed of a multicystic lesion and a solid lesion. Histopathologic examination of the multicystic lesion revealed that the locules were lined by biliary epithelium, demonstrating various degrees of cytological atypia. The stroma was fibrous, and the tumor showed marked apocrine snouts. Part of the tumor showed papillary growth with strong cytological atypia. The solid lesion showed tubulocystic proliferation of tumor cells, with prominent apocrine snouts, embedded in dense and partially hyalinized fibrous stroma. The morphology of the solid part was quite similar to that of reported biliary adenofibroma. Despite lengthy discussion, an appropriate pathological diagnosis could not be found among the current classifications of biliary tumor. The tumor was finally diagnosed as unclassified multicystic biliary tumor with adenofibroma features.

HLA antigen expression in melanocytic lesions: Is acquisition of HLA antigen expression a biomarker of atypical (dysplastic) melanocytes?

Although criteria are established for the histologic diagnosis of atypical nevi (AN), consensus about the criteria in the diagnosis of and in the definition of AN is limited. Moreover, intraobserver and interobserver differences in the application of these criteria for the diagnosis of AN have been observed. We sought to determine the usefulness of HLA antigen expression as a biomarker of AN. The immunoperoxidase reaction was used to mark common nevi and AN with HLA class I heavy chain-, β2microglobulin (β2m)-, and HLA class II β chain-specific monoclonal antibodies. HLA class I heavy chain, β2m, and HLA class II β chain were expressed in 5 (8.6%) of the 58 common nevi and in 46 (∼72%) of the 64 atypical melanocytic lesions. Among common lesions, only halo nevi expressed HLA class I heavy chain, β2m, and HLA class II β chain. The level of HLA class I heavy chain β2m and of HLA class II β chain expression correlated with the degree of cytologic atypia and architectural disorder. The number of lesions tested and the subjective nature of the analysis of immunohistochemical staining of tissue sections are both limitations. The data presented suggest that HLA antigen expression is an objective biomarker that correlates well with the degree of cytologic atypia in AN and may: (1) be useful to distinguish common nevi from AN, and (2) represent a more objective measure to determine which AN should be excised.

Morphologic and immunophenotypic analysis of desmoid-type fibromatosis after radiation therapy

The morphologic changes seen in desmoid-type fibromatosis after radiotherapy have not been well studied, and the degree of cytologic atypia, cellularity, mitotic activity, and lesional necrosis found in desmoid-type fibromatosis treated with ionizing radiation has not been thoroughly assessed. Therefore, we evaluated a series of primary and locally recurrent desmoid-type fibromatoses resected at variable intervals after radiation therapy (XRT) and compared their histopathologic and immunophenotypic features with paired pathologic specimens that were obtained before radiotherapy. The morphologic characteristics of desmoid-type fibromatoses resected before and after radiotherapy were not significantly different in 7 of the 8 cases studied. One case resected 191 months after XRT showed morphologic evidence of fibrosarcomatous transformation, with zonal necrosis, hypercellularity, severe nuclear atypia, and increased mitotic activity. No significant differences in the immunophenotype of desmoid-type fibromatosis were observed after XRT. In rare cases of recurrent desmoid-type fibromatosis, the differential diagnosis may include radiation-induced fibrosarcoma. Our data suggest that histomorphologic alterations attributable to the effects of ionizing radiation in desmoid-type fibromatosis are minimal. Therefore, the presence of cytologic features of malignancy in this setting warrants careful examination and consideration of the rare occurrence of postradiation sarcoma. Lesser degrees of nuclear atypia seen in isolation do not necessarily indicate a poor prognosis in irradiated desmoid-type fibromatosis.

An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

Significance of epidermal growth factor receptor expression in the grading of phyllodes tumors of the breast

Background and aim: Limited studies on the relationships between epidermal growth factor receptor (EGFR) expression and the grades of phyllodes tumors (PT) of the breast were reported. This study evaluated the significance of EGFR overexpression in the grading of PT. Methods: Immunohistochemical stain for EGFR was done in 46 PT cases. The differences of EGFR expression according to the degrees of cytologic atypia and mitotic count and between benign, borderline and malignant PTs based on Rosen or World Health Organization (WHO) criteria were analyzed. Results: Significant differences of positive (moderate membranous and cytoplasmic, more than 10% of tumor cells) and strong positive (moderate more than 50% of tumor cells) reactions for EGFR were found according to the degree of cytologic atypia (P= 0.0016 and P= 0.0122) and between the PTs showing ≤5 mitoses and >5 mitoses/10 high power field (P= 0.0230 and P= 0.0058). Positive reaction for EGFR was more common in borderline/malignant PTs than benign PTs, and strong positive reaction for EGFR was relatively common in malignant PTs. Conclusions: Epidermal growth factor receptor overexpression, more than 10% of tumor cells, could be used as an ancillary tool for the discrimination of benign from borderline and malignant PTs.

Uterine smooth muscle tumors of uncertain malignant potential and atypical leiomyoma: A morphological study of these grey zones with clinical correlation

To study the histological features in uterine STUMP, and atypical leiomyomas (AL), and to correlate with clinical outcome. From January 2004 to August 2010, a total of 21 cases were retrieved from records, labeled as STUMP(7), AL (5), AL with low risk of recurrence (2), smooth muscle tumor of low malignant potential (STLMP) (2), and symplastic leiomyoma (5). The slides were reviewed for coagulative tumor cell necrosis (CTCN), hyaline necrosis/ infarction type necrosis, presence and degree of cytological atypia, mitotic activity, epithelioid morphology and myxoid features. The other characteristics (such as size, circumscription, individual tumor cell necrosis), were noted, wherever available. The mean age was 45 years (median 46; range 24-67 yrs). CTCN was seen in 2 cases on examination of additional material; wherein a revised diagnosis of leiomyosarcoma had been given. Infarction type necrosis and individual cell necrosis was seen in 2 and 3 cases, respectively. Mitoses were less than 5/10 hpf in all the cases. One of the tumours labeled as STUMP also had concurrent endometrial adenocarcinoma. Follow up: Follow-up was available in 11 cases (52.3%). One patient had died. (cause not known). In 10 patients, the follow-up ranged from 4 to 56 months (mean 20.9 months; median 15 months) nine patients were alive and well. One patient (labeled STLMP) had metastatic liver disease 3 yrs after the primary surgery, at the last follow-up. 1) There is an overlap in using the terminologies as STUMP, AL, AL with low risk of recurrence, AL with low malignant potential. A designation of STUMP does convey a category of borderline malignancy to the gynecological surgeons. Most behave in a benign fashion and follow-up without adjuvant therapy is currently recommended. Critical evaluation of coagulative tumor necrosis is essential. Follow-up remains a challenge in our setting.

Flat ductal intraepithelial neoplasia of the breast: evolution of Azzopardi's “clinging” concept

Thirty years ago, John G. Azzopardi described a mainly cytologically defined atypical intraepithelial lesion of the breast, which he called "clinging carcinoma in situ," a variant of "ductal carcinoma in situ." The lesion was characterized by replacement of native epithelial cells by very few cell layers of mildly to severely atypical epithelial cells. Based on the degree of cytologic atypia, Azzopardi distinguished type 1 with highly atypical nuclei and type 2 with merely subtle cytologic (nuclear) atypia. Although this distinctive lesion remained widely unrecognized and/or ignored by many pathologists for a long period, several recent studies strongly suggest its neoplastic nature. The aim of this review is to focus on the "clinging" concept and its evolution after the first description. The diagnostic criteria, main diagnostic pitfalls, immunohistochemistry, molecular-genetic findings, and the relevance of this type of lesion for clinicians and histopathologists are discussed. Rational for adopting a more appropriate terminology and classification, namely flat ductal intraepithelial neoplasia are also discussed. It is concluded that the "clinging" or flat lesion represents one of the earliest morphologically recognizable neoplastic breast lesions. This lesion is important, if one tries to better understand the tumorigenesis of early precursor lesions of the breast. This type of breast lesion is an indicator for coexisting neoplastic lesions, such as low-grade ductal intraepithelial neoplasia (atypical ductal hyperplasia/low-grade ductal carcinoma in situ) and lobular intraepithelial neoplasia.

Prognostic significance of grading in lung adenocarcinoma

Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma. The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count. In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern > or = 90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002). The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma.

Histiocyte‐rich pleomorphic mastocytoma: an uncommon variant mimicking juvenile xanthogranuloma and Langerhans cell histiocytosis

An 11-year old Caucasian female with a remote history of urticaria pigmentosa presented with a neck mass. A biopsy demonstrated a large intradermal nodule composed of unusually large epithelioid mast cells, including a prominent subset with bi-lobed and multi-lobed nuclei. By immunohistochemistry, the cells expressed CD117 (C-Kit), mast cell tryptase, CD68, and CD25, and were negative for CD163, CD1a, and S-100, confirming the diagnosis of mastocytoma. Equally prominent was an admixed infiltrate of CD68 and CD163-positive xanthomatous histiocytes that included Touton-type giant cells. Eosinophils were abundant. At 7 months follow-up, there was no recurrence of the lesion following complete excision. However, given the unusual cytologic features, close clinical observation is warranted, as the long-term biologic potential of mastocytoma with this degree of cytologic atypia is uncertain. Awareness of this unusual morphologic variant is also important as the histologic features may mimic such childhood neoplasms as juvenile xanthogranuloma and Langerhans cell histiocytosis.

A scoring system for histopathologic and immunohistochemical evaluations of uterine leiomyosarcomas

Uterine leiomyosarcomas (LMS) are difficult to distinguish from benign leiomyomas without surgery. In this study we performed transcervical needle biopsy on 475 patients, 8 LMS patients and 467 patients with non-sarcomas (non-LMS) in a high-risk group for LMS, and evaluated whether examinations performed with Ki-67 and CD34 immunohistochemical analyses in addition to the standard hematoxylin-eosin (H&E)-stained sections would improve preoperative diagnostic precision of the uterine smooth muscle tumors. Histopathologic analysis included three factors: degree of cytologic atypia, mitotic index and coagulative tumor cell necrosis (CTCN). We also evaluated cell proliferation with Ki-67 expression. In cases of suspected CTCN, we examined CD34 expression and counted positive blood vessels in the necrotic area. Three of the 8 LMS cases satisfied the diagnostic criteria of LMS by histopathologic evaluation with H&E-stained sections. We made a score list based on these analyses; scores for LMS specimens ranged from 6-14 points; non-LMS specimens scored 0-2 points. At the cut-off score of 6 points, the positive predictive value to distinguish LMS from non-LMS was 100%, showing that this scoring system, is a useful method for preoperative differentiation between LMS and non-LMS tumors.