Degree Of Pleomorphism Research Articles

Ring Chromosomes and Associated Disorders: A Review

Ring chromosomes are formed due to rejoining or breaking in either one or both the chromosome arms. Any chromosome can form such structure and thus a specific ring chromosome will have an altogether distinct size and inherited content. Of intrigue are ring chromosomes 14 and X that have a remarkable relationship with epilepsy and seizure beginning in early years of life. Phenotypic characteristics associated with ring chromosomes are very much disparate and this may be due to any deletion caused by ring arrangement. Other reason may be the imbalances occurred due to ring instability. Extreme deficiency of development without major deformity is a very usual observation in the carrier of the ring chromosomes. Such phenotypic expressions are termed as "ring disorder" and they are strictly related with mitotic instability and ring behavior and does not dependent on the chromosome engaged. In case of ring chromosomes, it is not possible to exactly correlate genotype-phenotype because all the determining factors mostly variegate depending on the magnitude of deletion during ring development. Also, ring instability and the level of mosaicism add extra degree of pleomorphism. In spite of the fact that ring chromosomes generally emerge as de-novo events, filial transmission of rings from carrier to progeny is portrayed and pre-birth diagnosis for any pregnancies should be appraised.

Cutaneous metastasis of invasive ductal carcinoma on FNAC: A case report

The cutaneous metastasis is a late uncommon manifestation of cancer and indicates poor prognosis. The cutaneous metastasis can be a first presentation of underlying malignancy. The FNAC is an easy tool for rapid diagnosis of cutaneous metastasis. A 47-year-old female, known case of invasive ductal carcinoma presented to hospital with history of multiple nodular skin lesions over the body varying in size from 0.5-1.5 cm from past 2 months. The smears were cellular and comprises of loose clusters and singly scattered atypical epithelial cells, displaying moderate degree of pleomorphism with mild amount of cytoplasm, large irregular nucleus with fine to coarse chromatin, inconspicuous to conspicuous nucleoli and occasional atypical mitosis against a lipohemorrhagic background. The diagnosis of metastatic deposits of invasive ductal carcinoma was rendered. The clinical diagnosis of metastatic deposits can be challenges, especially in case of distant metastasis or when the cutaneous metastasis is the first presentation. The cutaneous metastasis can be confused clinically as adnexal lesion. The use of special stains and immunohistochemical markers can aid in diagnosis.

Hormone receptor expression, clinical and histopathological analysis in feline injection site sarcomas.

Feline injection site sarcomas (FISS) are aggressive, with high recurrence and rarely metastasising. The objective of this study was to evaluate, by immunohistochemistry, the expression of oestrogen (ER) and progesterone (PR) receptors in FISS and correlate them with clinical and histopathological aspects. This was a retrospective study with 51 cases of FISS. Immunohistochemistry was performed to detect vimentin, ER, PR and Ki67 expression. Clinical, histopathological and immunohistochemical characteristics were predictor variables and the expression of ER and PR were the dependent ones. Twenty-eight (55%) of the 51 FISS cases were female and 23 (45%) male with 10.7 ± 4.2 years and median tumour size of 3cm (2.0-5.4). The trunk was the most affected site, with 38 cases (84%). Histological grade III was observed in 57% of the cases, considering differentiation score, necrosis and mitotic index. ER expression, positive in 64% of cases, was associated with the mitotic index (P=.05) and degree of pleomorphism (P=.04). PR was not associated with the variables and 63% of cases were negative for this receptor. Thus, ER expression can affect tumour growth. The knowledge on the FISS hormonal expression is important to clarify the pathophysiological mechanisms. Further studies are needed to predict the value of ER expression in the prognosis of FISS.

DYSPLASTIC MELANOCYTIC NEVUS IN THE ORAL CAVITY: MORPHOLOGIC AND IMMUNOHISTOCHEMICAL FINDINGS

A 35-year-old female patient attended the oral diagnostic service presenting with a lesion on the attached gingiva, in the region of dental elements 31 and 32. The lesion presented a red-blackish coloration, softened consistency, sessile implantation, and exophytic growth, measuring approximately 4 mm. An excisional biopsy was performed, and the diagnostic hypotheses of hemangioma and angiofibroma were considered. During microscopic examination, there was proliferation of nevus cells, organized in theques arrangements, exhibiting a certain degree of pleomorphism, hyperchromatism, and sometimes bizarre appearance. From the immunohistochemical analysis for HMB-45, Melan-A, S-100, and Ki-67 antibodies, the histopathologic diagnosis of dysplastic melanocytic nevus was given. This case emphasizes the importance of the association of clinical, histopathologic, and immunohistochemical characteristics to obtain an adequate diagnosis, to rule out any other lesions. A 35-year-old female patient attended the oral diagnostic service presenting with a lesion on the attached gingiva, in the region of dental elements 31 and 32. The lesion presented a red-blackish coloration, softened consistency, sessile implantation, and exophytic growth, measuring approximately 4 mm. An excisional biopsy was performed, and the diagnostic hypotheses of hemangioma and angiofibroma were considered. During microscopic examination, there was proliferation of nevus cells, organized in theques arrangements, exhibiting a certain degree of pleomorphism, hyperchromatism, and sometimes bizarre appearance. From the immunohistochemical analysis for HMB-45, Melan-A, S-100, and Ki-67 antibodies, the histopathologic diagnosis of dysplastic melanocytic nevus was given. This case emphasizes the importance of the association of clinical, histopathologic, and immunohistochemical characteristics to obtain an adequate diagnosis, to rule out any other lesions.

A clinical analysis of 14 cases of prostatic stromal tumor of uncertain malignant potential

To investigate the clinical and pathologic characteristics, diagnosis, treatment, prognosis and survival of prostatic stromal tumor of uncertain malignant potential. Overall 14 patients with prostatic stromal tumor of uncertain malignant potential were treated from October 2008 to April 2020, the patient age ranged from 27 to 78 years (mean 54 years). The disease duration was 1 to 180 months (mean duration of 46 months). The clinical manifestations mainly included urinary obstructive symptoms and urethral irritating symptoms. The tumors were located in the peripheral zone or the transition zone. Digital rectum examination indicated prostatic tumor. Serum prostatic specific antigen level was always normal or elevated. Transrectal ultrasonography and magnetic resonance imaging indicated prostatic tumor. Magnetic resonance imaging in showed large, round, well-defined masses, which were diffusely heterogeneous signal on T2 weighted imaging. Following the administration of intravenous contrast medium, the lesion had diffuse and heterogeneous enhancement. In the study, 3 cases underwent prostate biopsy, 2 cases underwent transurethral resection of the prostate, 9 cases underwent radical excision or transurethral resection of the prostate with definite diagnosis of pathologic features. Under the light microscope, the interstitial cells of stromal tumor of uncertain malignant potential were overgrowth and fusiform cells showed some degree of pleomorphism, nuclei with few mitotic figures, and necrosis was not often seen. Immunohistochemical staining showed that prostate specific antigen was negative, while vimentin was positive in the tumor tissue, CD34, progesterone receptor and smooth muscle actin were positive in the majority, and Ki67 positive index was 1%-20% (mean 6%). Twelve cases were followed-up, and the time of survival varied from 10 to 96 months (mean 65 months), two cases were lost to the follow-up, one case died of disease at the end of 10 months, nine cases were free of disease recurrence after surgery, two cases underwent more transurethral resection of the prostate due to local recurrence. STUMP is a very rare tumor of the specialized prostatic stroma with an unpredictable clinical behavior. The clinical manifestations, transrectal ultrasonography and magnetic resonance imaging are valuable for the diagnosis of prostatic stromal tumor of uncertain malignant potential. Its definite diagnosis depends on pathological examination. Up to now, early surgery and combined therapy are effective treatments for prostatic stromal tumor of uncertain malignant potential.

JAK-2-Positive Latent Myeloproliferative Neoplasms with Splanchnic Vein Thrombosis- from the Hematopathology Perspective

Introduction: Philadephia-negative Myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The diagnosis of MPNs and further sub classification are based mainly on WHO diagnostic criteria which rely on the presence of an evidence of single or multiple cell lineage proliferation reflected by elevated hemoglobin, and / leukocytosis and /thrombocytosis. In addition, to presence of certain pathologic features in the bone marrow (BM) including hypercellularity , panmyelosis, proliferation of megakaryocytes, the presence of atypical megakaryocytes and or increased marrow fibrosis. This is in addition to the presence of molecular genetic marker specific for MPN including JAK-2, MPL and CALR. Making a diagnosis of MPN in absence of the previously mentioned features is always challenging. Herein, we analyze the clinical, pathologic and molecular genetics features for five cases presented with splanchnic vein thrombosis and found to be positive for JAK-2 V617F. However, from the hematpathologic point of view, apart from JAK-2 positivity, none of these cases had fulfilled the WHO diagnostic criteria for MPNs. Although the BM specimens were reviewed by at least two experienced hematopathologists, it was so difficult to conclude the diagnosis and or do further sub classification into a specific MPN category. Objective: The aim of this report is to highpoint the difficulty in establishing the diagnosis within this group of patients based on the current WHO diagnostic criteria, to focus on BM pathologic features of this group of patients. Patients and Methods: The patients reported here were referred to our center presenting with portal vein, superior mesenteric or splenic vein thrombosis. Five adult female patients were recognized (2015 and 2019). The mean age at diagnosis is 40.8 years (27-56). None of these cases had an increase in peripheral blood counts except for patient (1) which had mild leukocytosis and thrombocytosis. All patients showed normocellular or slightly hypercellular BM. Slight erythroid predominance was reported in patient (2) and (4). Megakaryocytes were increased in all patients except for patient (2). Interestingly, megakaryocytes morphology was similar in all five patients as they showed anisocytosis with some degree of pleomorphism with predominant of large forms, no clustering and no abnormal topography was noted (figure 1 and 2). All patients showed no significant increase in reticulin fibrosis. Sub-classification into a specific MPN category cannot be performed in all patients. Next generation sequence had been used to analyze targeted regions in recurrently mutated genes in myeloid neoplasia. JAK-2V617F mutation was detected in all studied patients. In patient number (2) JAK-2 mutation was detected at a low level (4%), however, on follow-up, the mutation level increased in addition to detection of 3bp insertion/deletion in CALR gene resulting in a mutation other than type I or type II. table (1). Discussion: Splanchnic veins thrombosis (SVT) includes the portal vein thrombosis (PVT), mesenteric (MVT) splenic vein thrombosis, and the Budd Chiari syndrome (BCS). SVTs are rare events, estimated by 0.7 per 100,000 patients per year for PVT [Rajani et al. 2010]. In a laboratory setting, the diagnosis of latent MPN in patients with SVT is challenging due to absence of elevated blood counts, probably caused by portal hypertension and splenomegaly that result from SVT and MPN. However, the reason why this group of patients does not have overt features of myeloproliferation (particularly) the hypercellularity in the BM is not yet clear. It is possible that JAK-2 positivity induced venous thrombosis longer time before development of the full blown picture of MPN. However, follow-up BM studies for this group of patients might help in better characterization of the pathologic features of these patients. These patients are included in the MPN, unclassifiable subcategory in the current WHO classification. However, based on our findings and the previously published data it seems that these patients have distinctive clinical and pathological features that necessitate having them in a separate MPN entity that might have less strict diagnostic criteria that might include clinical symptoms especially venous thrombosis in large vessels. Separating this group of patients will help to study them thoroughly. Disclosures No relevant conflicts of interest to declare.

A Novel Curvature - Norm Based Centroid Initialized and Morphologically Driven Distance Regularized Level Sets for Nuclear Segmentation in Histopathological Images

Nuclear pleomorphism is considered to be one of the most significant shape based feature adapted in grading the cancer through the pathological studies of the H&E stained tissue slides. Microscopic study of manually extracting the feature is highly laborious and misleads the pathologists during grading. Digitization of the slides has given rise to various segmentation approaches to extract the nuclei shape to assess the degree of pleomorphism. Here, a novel approach of initializing and evolving the distance regularized level sets (DRLS) for the detection and segmentation of the nuclei has been presented. In this work, two major objectives have been achieved. First, a novel geometric approach has been devised for the detection of centroids of each nuclei in the occluded region and second, a shape prior model has been presented for the extraction of gradient information through morphological operations. The multiple level set implementation of the DRLS contours are initialized using the centroids detected and driven through the gradient computed. The proposed method has been experimented over the images of benign and malignant breast cancer tissue obtained from BeakHis dataset. A quantitative analysis of the results have shown that a 97% of object detection accuracy and 78% of overlap resolution has been achieved through the proposed model. A comparative study with that of geodesic active contours have indicated an improvement in the segmentation accuracy measure of 9-10 pixel difference.

The Prevalence of Prostatic Stromal Tumor of Uncertain Malignant Potential in Specimens Diagnosed as Prostatic Hyperplasia.

Prostatic stromal tumors of uncertain malignant potential (STUMPs) are rare tumors arising from the specialized prostatic stroma. These tumors share certain histological and clinical features of benign prostatic hyperplasia, resulting in misdiagnosis of STUMP as prostatic hyperplasia. However, in contrast to prostatic hyperplasia, occasional cases have been documented to recur rapidly after resection and few of them have progressed to prostatic stromal sarcoma and distant metastasis. In this study, we aimed to estimate the prevalence of prostatic STUMP in specimens initially diagnosed as prostatic hyperplasia. A total of 702 consecutive pathology slides with a diagnosis of prostatic hyperplasia between 2009 to 2014 in specimens were obtained by prostatectomy or trans- urethral resection of the prostate. Those slides were submitted to Faghihi hospital, affiliated to Shiraz University of Medical Sciences, and were reviewed retrospectively in order to search the findings in favor of STUMP. Based on histological findings, STUMP was identified in 3 cases (0.43%), which revealed hypercellular stroma, infiltrating between the hyperplastic glands. Cells showed some degree of pleomorphism, nuclei with vesicular chromatin and few mitotic figures. No recurrence was reported in patients. Although STUMP can be histologically and clinically misdiagnosed as BPH, the differences in prognosis and treatment modalities highlight the importance of rendering the correct diagnosis.

Histologic Features Associated with Deep Invasion in Dermatofibrosarcoma Protuberans

BackgroundDermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing cutaneous tumor that can invade the subcutaneous tissue, muscle tissue, and even bone. ObjectiveTo identify histologic features associated with greater depth of invasion, i.e., local aggressiveness, in DFSP. Material and methodsWe analyzed associations between histologic features of DFSP (e.g., type of subcutaneous invasion, histologic pattern, cell type, areas of fibrosarcoma) and the presence and absence of muscle fascia involvement. ResultsWe studied 155 cases of DFSP. The following histologic characteristics were significantly associated with involvement of the muscle fascia: the presence of a sheetlike pattern, a high degree of cellular pleomorphism, and more than 1 mitotic figure. The tumor did not extend beyond the subcutaneous tissue in the majority of cases (62.6%), but there was involvement of the fascia or galea aponeurotica in 17 cases (11%) and of the muscle tissue in 36 cases (23.2%). ConclusionsHistologic patterns, degree of pleomorphism, and number of mitotic figures are important predictors of deep invasion (fascia or muscle) in DFSP; these layers can be involved in up to 30% of cases.

Estudio de los factores histológicos asociados a la infiltración en profundidad en el dermatofibrosarcoma protuberans

BackgroundDermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing cutaneous tumor that can invade the subcutaneous tissue, muscle tissue, and even bone. ObjectiveTo identify histologic features associated with greater depth of invasion, i.e., local aggressiveness, in DFSP. Material and methodsWe analyzed associations between histologic features of DFSP (e.g., type of subcutaneous invasion, histologic pattern, cell type, areas of fibrosarcoma) and the presence and absence of muscle fascia involvement. ResultsWe studied 155 cases of DFSP. The following histologic characteristics were significantly associated with involvement of the muscle fascia: the presence of a sheetlike pattern, a high degree of cellular pleomorphism, and more than 1 mitotic figure. The tumor did not extend beyond the subcutaneous tissue in the majority of cases (62.6%), but there was involvement of the fascia or galea aponeurotica in 17 cases (11%) and of the muscle tissue in 36 cases (23.2%). ConclusionsHistologic patterns, degree of pleomorphism, and number of mitotic figures are important predictors of deep invasion (fascia or muscle) in DFSP; these layers can be involved in up to 30% of cases.

Abstract P6-10-18: Phyllodes tumor of the breast, clinicopathological features and prognostics factors in a retrospective cohort with 7-year follow-up

Abstract BACKGROUND: The phyllodes tumor of the breast is a rare neoplasm that represent less than 1% of all breast tumors and between 2.5% of fibroepithelial tumors. Often develop local recurrence and more infrequently metastatic capability. OBJECTIVE: The aim of this study was to describe clinical pathological characteristics and identify prognostics factors in terms of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with phyllodes tumors of the breast. METHODS: We retrospectively analyzed 157 patients diagnosed and treated at the "Instituto Nacional de Enfermedades Neoplasicas" between January 2005 to December 2010. In order to evaluate the relationship between clinical features and histology of the tumors, the Pearson χ2 test was used. Kaplan-Meier method with Log-rank test or Breslow test (when it was applicable) was used to identify prognostic factors in terms of LRFS, DMFS and OS. RESULTS: The median age was 42 years (range: 13-81 years), 98 (62.4%) cases ≤ 45 years and 59 (37.6%) cases > 45 years; 88 (56.1%) had tumors in the right breast, 67 (42.7%) in the left breast and 2 (1.3%) had bilateral tumor. The mean of tumor size was 6.3 cm (range: 0.7-30 cm). Sixty three (40%) tumors were ≤5 cm and 94 (59.9%) were >5cm. Regarding the histological classification, 100 (63.7%) cases were benign, 35 (22.3%) were borderline and 22 (14%) were malignant. Age (p=0.047), tumor size (p=0.001), atypical stromal (p=0.066), stromal cellularity (p<0.001), pleomorphism (p<0.001) and tumor necrosis (p=0.003) were associated to the histological type. Local recurrence occurred in 9 patients, 2 developed distant recurrence and 1 patient presented synchronously local and metastatic recurrence. In the univariate analysis, histological subtype (p=0.006) and pleomorphism (p<0.001) were identified as prognostic factors of LRFS, while the surgical approach (p=0.008), histological type (p<0.001) and some histological features such as stromal cellularity (P<0.001), pleomorphism (p<0.001), heterologous elements (p<0.001) and tumor necrosis (p=0.004) were identified as prognostic factors for DMFS. In regard to the OS, we found as prognosis factors, histology (p= 0.044), pleomorphism (p<0.001) and tumor necrosis (p=0.001). CONCLUSIONS: In our institution we have a low incidence (2.3%) of Phyllodes tumors of the breast and the majority of our patients were benign tumors and had good prognosis. We found that histological type and degree of pleomorphism are prognostic factors at LRFS and OS. Surgical approach, histological type and some histological characteristics were predictors for DMFS. Keywords: Phyllodes tumor, local recurrence, distant recurrence, overall survival. Citation Format: Morante Z, Araujo J, Fuentes H, Neciosup S, Gomez H. Phyllodes tumor of the breast, clinicopathological features and prognostics factors in a retrospective cohort with 7-year follow-up. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-18.

Esthesioneuroblastoma

The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/- adjuvant chemoradiation. A retrospective review of 27 patients with ENB was performed. The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome. There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohort's mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis. An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.

Morphological changes to endothelial and interstitial cells and to the extra-cellular matrix in canine myxomatous mitral valve disease (endocardiosis)

Morphological and functional changes in endothelial and interstitial cells are considered central to myxomatous degeneration of the canine mitral valve (endocardiosis). The aim of this study was to describe and quantify changes in valve endothelial cells (VECs), interstitial cells (VICs) and the extra-cellular matrix (ECM) of the sub-endothelial zone of diseased valves using a combination of transmission electron microscopy, stereology and computer-aided image analysis.Marked degradation of the endothelium was evident in diseased valves, which coincided with significant degradation of the local ECM (P<0.001). There were decreases and increases in the numbers of VECs and VICs, respectively, in diseased valves, with particular accumulation of VICs subjacent to the valve surface (P<0.01). Overall, VICs were more pleomorphic than VECs in both normal and diseased valves, but for VECs, the degree of pleomorphism was significantly different in diseased valves (P<0.0001). The findings of the study confirm that canine myxomatous mitral valve disease is associated with marked endothelial damage, with attendant proliferation of subjacent activated myofibroblasts. The fact that similar endothelial changes are present in normal valves suggests these processes not only contribute to valve pathology, but may also represent life-long valve remodelling.

The cytomorphologic spectrum of Wilms tumour on fine needle aspiration: a single institutional experience of 110 cases

To analyse the cytomorphologic spectrum of Wilms tumour (WT) on aspirates, the largest series reported to date. Adequate aspirates from paediatric renal tumours over a period of 17 years were reviewed and selected if subsequent excision showed WT or aspirates were diagnostic for WT and clinical/radiological evidence consistent with that diagnosis. Smears were re-examined for the proportion of components, degree of pleomorphism and mitosis. Of 110 aspirates, smears were triphasic in 44 (40.0%), biphasic (blastema and tubules) in 36 (32.7%) and monophasic (blastema alone) in 30 (27.3%). Stromal predominance was seen in 11 aspirates (10.0%) and five showed rhabdomyoblastic differentiation; all 11 were triphasic. Mean mitotic rate was 9.3/5000 cells (range 4-39/5000). Nuclear atypia not amounting to anaplasia and without atypical mitoses was seen in 15 (13.6%); these presented diagnostic problems. Two aspirates (1.8%) were considered anaplastic (unfavourable), both having atypical mitoses. Criteria similar to histology (i.e. 3-fold or more variation in nuclear size, marked hyperchromasia with bizarre nuclei and atypical mitoses in a biphasic or triphasic aspirate) helped in distinguishing anaplastic WT. Histopathological correlation in 67 cases showed good correlation of blastemal predominance, stromal predominance and anaplastic histology with the corresponding cytology. However, 9/27 (33.3%) triphasic tumours had only blastemal cells on corresponding aspiration because of sampling error. Cytokeratin was positive in 4 of 20 aspirates with blastema alone. Aspirates from WT were triphasic or biphasic in the majority (72.7%), permitting cytological diagnosis, which was improved by cytokeratin immunocytochemistry. Blastemal and stromal predominance on histology correlated well with cytology, but many triphasic tumours showed only blastema on aspiration. Anaplastic WT can be detected on aspirates using criteria similar to histology.

Malignant Glomus Tumour: A Case Report and Review of the Literature

Purpose: Glomus tumours are characteristically benign solitary tumours. At our knowledge, about 23 reports are present in literature regarding the malignant counterpart, but only a minority developed metastases. We describe a locally aggressive glomus tumour with lymphnode metastasis. Patient: The patient was a 40 year-old man presenting a 1.5-cm lesion on the right wrist incompletely excised and a recurrent tumour, 4 × 2 cm in size, removed after 9 months, for which he received radiotherapy. After 2 years he developed an axillary lymphnode metastasis. Results: Histologically, both tumours (primary and metastasis) were similar. There were sheets and nests of uniform small cells with scant eosinophilic cytoplasm and round to polygonal nuclei; there was some degree of pleomorphism and the mitotic index was high (up to 18 m/10 HPF). The tumour cells were positive for vimentin and smooth muscle actin, but negative for desmin, NSE, Factor VIII, chromogranin, cytokeratin. Remarkably, in the primary, the cells strongly expressed p53 (70%) and MIB-1 (35%). Discussions: In many reported malignant cases, the histology of the tumour cells suggested that they were malignant, yet the clinical course has been benign. Carefully reviewing the literature, it seems that actually we have enough histological criteria to identify the cases with biological adverse outcome. Those unfortunate cases behave as high grade sarcomas and therefore may deserve an aggressive therapeutic treatment.

A comparative review of melanocytic neoplasms.

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.

Imaging human epithelial properties with polarized light-scattering spectroscopy.

Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology developed to probe the structure of living epithelial cells in situ without need for tissue removal. LSS makes it possible to distinguish between single backscattering from epithelial-cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative information about the epithelial-cell nuclei such as nuclear size, degree of pleomorphism, degree of hyperchromasia and amount of chromatin. LSS imaging allows mapping these histological properties over wide areas of epithelial lining. Because nuclear enlargement, pleomorphism and hyperchromasia are principal features of nuclear atypia associated with precancerous and cancerous changes in virtually all epithelia, LSS imaging can be used to detect precancerous lesions in optically accessible organs.

Pathologic characteristics of primary cutaneous T-cell lymphoma in Korea.

Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of peripheral T-cell lymphomas arising in the skin and show considerable variations in clinicopathological features. This study was designed to examine viral genomes and cellular proliferation markers in CTCLs arising in Korea. On the basis of their morphologic characteristics and immunophenotypes, 43 cases of primary CTCL were classified, and evaluated for association with either HTLV-I or EBV, p53 protein immunoreactivity and Ki-67 labeling index (LI). EBV was demonstrated in 15 cases (35%) either by EBER in-situ hybridization or PCR; particularly high rates were exhibited by angiocentric T-cell lymphomas. PCR was used to detect HTLV-I proviral DNA, but none was found. The p53 expression rate was higher in large cell lesions, but the Ki-67 LI failed to show any significant differences among the different types. We therefore concluded that in Korea, HTLV-I is less frequently associated with CTCL than in other endemic countries. EBV was found particularly in angiocentric lesions, regardless of cell size or degree of pleomorphism. Because of its high positive rates in high grade lesions, the p53 expression showed positive correlation with histologic grade; however, the Ki-67 labeling index did not correlate with the histologic grade in CTCL.

Nodular fasciitis — Part II. A rare cause of a lump in the breast in a 44-year-old woman

A 44-year-old lady presented with a 6 month history of a painless lump in the left breast. She was pre-menopausal with no family history of breast disease. She had been on the oral contraceptive pill for 2 years and breast fed one child. On examination there was a 1 cm solid nodule in the upper central portion of the left breast which was mobile and superficial and had the clinical features of a fibroadenoma. There was no associated lymphadenopathy. Fine needle aspiration cytology showed metachromatic stroma and benign pairs of ductal epithelial cells suggestive of fibroadenoma, but there was some degree of pleomorphism. The mammogram demonstrated an irregular density, 1.5 cm in diameter with a central lucency consistent with a sclerosing lesion (Fig. 1). In view of the pleomorphism seen in the cytology specimen, it was decided to excise the lump for histological examination. The excised lump appeared macroscopically as a firm white nodule 0.7 cm in diameter. The histology showed a focally storiform spindle cell proliferation with an infiltrative margin. The cytology of the spindle cells was bland and there was sparse mitotic activity, but no abnormal forms were seen. There were inflammatory cells and foci of mucoid change together with micro-haemorrhage. The appearances were those of nodular fasciitis (Fig. 2).

Well differentiated and small cell neuroendocrine carcinomas of the lung. Two related but distinct clinicopathologic entities.

Twenty-two resected pulmonary well differentiated neuroendocrine carcinomas (WDNC) were re-evaluated histologically as were 28 resected intermediate-small cell neuroendocrine carcinomas (IC-SCNC). WDNC were distinguishable from IC-SCNC by their consistently recognizable organoid architecture, and by the absence or limited extent of necrosis. Furthermore, WDNC could be subclassified into 3 subsets based upon the degrees of pleomorphism, local and vascular invasion, and stromal fibrosis, the mitotic count, and the extent of tumor necrosis. Whereas all those parameters were important in discriminating between WDNC and IC-SCNC, the quality of the organoid architecture, and the extent and pattern of necrosis emerged as the most significant. WDNC with the more aggressive histologic features (subset III) had, as a group, a distinctly worse clinical course that those displaying blander features (subsets I and II). Nevertheless, even subset III of WDNC had, as a group, a longer survival than similarly treated Stages I and II IC-SCNC. We conclude that the histologic spectrum of WDNC is broader than generally recognized. Moreover, 3 subsets of WDNC are definable based on conventional histologic criteria provided sufficient, well preserved samples are examined. Even the most aggressive subset of WDNC can be thus histologically discriminated from IC-SCNC, and, given comparable stages, has a better prognosis than the latter.