The flow cytometry of melanocytic skin lesions

DNA flow cytometry was performed on formalin fixed, paraffin embedded melanocytic naevi. DNA aneuploidy was detected in all three types of naevus but was significantly more frequent in those naevi accepted as precursors of malignancy: that is, dysplastic and congenital pigmented hairy naevi. It may be that the presence of DNA aneuploidy has prognostic significance in these naevi. Technical problems were encountered in the analysis of data from melanocytic lesions so that caution is recommended in interpretation of studies using formalin fixed tissue.     

Clinicopathological features of elevated lesions of the duodenal bulb

We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion.     

Histopathologic interobserver agreement on the diagnosis of melanocytic skin lesions with equivocal dermoscopic features: a pilot study

AIMS AND BACKGROUND: Dermoscopy (dermatoscopy, skin surface microscopy, epiluminescence microscopy) has been increasingly employed in recent years for the preoperative detection of cutaneous melanoma, and dermatoscopic features of pigmented skin lesions have been previously defined using histopathology (HP) as the "key to the code". The aim of the present study was to evaluate the interobserver agreement on the HP diagnosis in a series of epiluminescence microscopy equivocal melanocytic skin lesions. STUDY DESIGN: Ten melanocytic skin lesions were selected on the basis of diagnostic disagreement of at least 2 out of 9 epiluminescence microscopy observers. The histologic specimens from the 10 lesions were examined by 9 HP observers. The agreement of the HP diagnoses was calculated by means of Fleiss' k statistics. RESULTS: The overall HP agreement was less than excellent (k = 0.5). When considering the prevailing epiluminescence microscopic and HP diagnoses, 2 cases were shown to be epiluminescence microscopy false-negative melanomas. Virtually no agreement was found among epiluminescence microscopy observers in 4 cases (40%) or among HP observers in 3 cases (30%). However, only one pigmented skin lesion remained unclassifiable on epiluminescence microscopy as well as HP. CONCLUSIONS: When at least 2 epiluminescence microscopy experts disagree in the evaluation of a given melanocytic skin lesion, even HP consultations may give equivocal results. The need to establish more reliable epiluminescence microscopic and HP criteria by performing an improved and meticulous clinicopathologic correlation, e.g. by using telecommunication via Internet, is emphasized.     

Cyclin-dependent kinase 2 expression in human melanomas and benign melanocytic skin lesions

Cyclin-dependent kinase 2 (CDK-2) is strongly involved in regulating the progression of the cell cycle through G1/S checkpoint and S phase. Numerous studies demonstrated increased levels of CDK-2 (and also of its regulatory cyclins E and/or A) in different types of human tumours. Correlations found between the expression of those cell cycle regulators and progression and/or invasiveness of some tumours indicated the importance of CDK-2 as a potential prognostic marker. At the same time, in vitro studies of melanoma cell lines revealed melanocyte-specific regulation of CDK-2. The present study was aimed at examining levels of CDK-2 in human melanomas and benign pigmented lesions to evaluate whether it might be considered a potential molecular marker of melanoma progression. Expression of CDK-2 was determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 76 lesions including 41 primary cutaneous melanomas, 15 lymph node melanoma metastases (in eight cases correlated with primary tumours), three melanoma recurrences (two cases correlated with both primary and metastatic melanomas) and 17 nevi. Our results demonstrate that development and progression of melanoma are associated with changes in CDK-2 expression level. Statistical significance of the observed correlations indicates that CDK-2 may be a suitable prognostic marker for melanoma and perhaps also a target for chemotherapeutic drugs.     

Interobserver agreement of the dermoscopic diagnosis of 129 small melanocytic skin lesions

AIM AND BACKGROUND: Dermoscopic diagnosis of pigmented skin lesions is based on the evaluation of dermoscopic criteria (classical pattern analysis) and on alternative diagnostic methods, such as the ABCD (A, asymmetry; B, border; C, color; D, differential structures) rule based on the total dermatoscopic score. The aim of the study was to investigate the interobserver agreement of standard dermoscopic criteria between two observers and the diagnostic validity of dermoscopic diagnosis by pattern analysis and by the ABCD rule. STUDY DESIGN: The study included a total of 129 small (< or = 5 mm) melanocytic skin lesions selected from all lesions observed in consecutive patients between April 1996 and September 1998. Before surgery, each lesion was photographed with a Dermaphot. Dermoscopic images were examined independently by two observers to evaluate the presence or absence of standard dermoscopic criteria and to establish the dermoscopic diagnosis by pattern analysis and by the ABCD rule. RESULTS: Interobserver agreement for dermoscopic criteria varied from moderately good to good, with the highest agreement for radial streaks (k = 0.96) and the lowest for pseudopods (k = 0.49). Interobserver agreement was moderately good in dermoscopic diagnosis by pattern analysis (k = 0.48) and by the total dermatoscopic score (k = 0.44). The sensitivity and specificity of dermoscopic diagnosis by pattern analysis were 40% and 99%, respectively, for both observers. As regards the total dermatoscopic score (a cutoff score of < or = 5.45 vs > 5.45), sensitivity ranged from 80% to 100% and specificity from 48% to 59%. CONCLUSIONS: The study showed that the pattern analyses as well as the ABCD rule give a poor discrimination between benign and malignant lesions and do not add relevant information for management decision in small melanocytic lesions. However, close follow-up examinations of small equivocal melanocytic lesions using digital equipment allow evaluation of their dermoscopic features during progression and whether their rather commonly found atypical dermoscopic features are lost during their natural course of growth.     

Dermoscopic and histopathologic diagnosis of equivocal melanocytic skin lesions: an interdisciplinary study on 107 cases

BACKGROUND: Dermoscopy (dermatoscopy, epiluminescence microscopy) is increasingly employed for the preoperative detection of cutaneous melanoma; dermoscopic features of pigmented skin lesions have been previously defined using histopathology as the key to the code. In a preliminary study on 10 cases evaluated by nine dermoscopists and nine histopathologists, the authors experienced that when at least two dermoscopists disagree in evaluating a melanocytic lesion, even histopathologic consultations may give equivocal results. METHODS: One hundred seven melanocytic skin lesions, consecutively excised because of equivocal clinical and/or dermoscopic features, were retrospectively examined by eight dermoscopists and eight histopathologists; the diagnostic interobserver agreement was calculated by means of the Schouten k statistics. After histopathologic consultations, all 107 lesions underwent unblinded dermoscopic re-evaluation in order to find which dermoscopic features had given rise to histopathologic diagnostic difficulties. RESULTS: The interobserver ageement was good for both dermoscopy (k = 0.53) and histopathology (k = 0.74). Out of 48 cases evaluated by the dermoscopists in complete accordance, only 8 (16.7%) received at least one conflicting histopathologic diagnosis. Instead, among the remaining 59 cases with at least one disagreeing dermoscopic diagnosis, 21 (35.6%) received at least one disagreeing histopathologic diagnosis. The unblinded dermoscopic re-evaluation showed that five out of seven lesions with clear-cut regression structures were histopathologically controversial. CONCLUSIONS: At least for selected and reasonably difficult lesions, a diagnostic discrepancy among formally trained dermoscopists seems to be predictive for a diagnostic disagreement among histopathologists. Lesions showing clear-cut regression structures are prone to give some histopathologic disagreement.     

Kikuchi淋巴结炎的临床病理学观察

目的：探讨Kikuchi淋巴结炎的病因及临床特征,提高对Kikuchi淋巴结炎的认识,减少误诊。方法：对31例病理确诊为Kikuchi淋巴结炎的病例,结合临床特点和免疫组化进行分析观察。结果：31例中男性14例,女性17例,临床表现均为发热和浅表淋巴结肿大。所有的病例可见核碎片及淋巴细胞凋亡;淋巴结内出现片状或灶状形态多样的组织细胞增生。免疫组化标记CD45、CD68及CD3均为阳性表达。结论：本病病理形态以组织细胞增生为特征,主要是与组织细胞来源的淋巴瘤进行鉴别,免疫组化标记CD68及CD3阳性表达,对本病诊断有很重要的价值。该病属自限性疾病,预后多良好。     

Clinicopathological features of breast angiosarcoma

Background

Breast angiosarcomas are rare neoplasm. Due to its rarity, our therapeutic strategy is extremely limited. Therefore, we investigated the clinicopathologic features and examined the treatment for angiosarcoma compared with some literatures.

Methods

We conducted a retrospective chart and slide review of all patients in our division seen from 1997 to 2012 with a diagnosis of primary or secondary breast angiosarcoma at the National Cancer Center Hospital (Tokyo, Japan).

Results

Nine patients were diagnosed with breast angiosarcoma (six primary and three secondary cases). The median age of patients with primary angiosarcoma was 39 years (range 27–65 years). The median tumor size was 6.78 cm (range 3.0–8.8 cm). In the primary tumor, 4 patients had total mastectomy and 2 had a breast conserving surgery. 3- and 5-year disease-free survival (DFS) of the patients with primary angiosarcoma was 20 and 0 %. 5-year surviving rate of primary angiosarcoma was 50 %. In all patients with secondary angiosarcoma, recurrence was observed in all cases. But one case obtained long-term survival in local control therapy.

Conclusions

Our study demonstrates breast angiosarcoma exhibits high recurrence rates. Tumor size and surgical margin may be important factor to obtain long-term survival. In this point of view, total mastectomy with adequate tumor margin with early detection is desired. In case of recurrence, if it is local, surgery may be potentially curative.

     

Kikuchi淋巴结炎的临床病理学观察

目的:探讨Kikuchi淋巴结炎的病因及临床特征,提高对Kikuchi淋巴结炎的认识,减少误诊.方法:对31例病理确诊为Kikuchi淋巴结炎的病例,结合临床特点和免疫组化进行分析观察.结果:31例中男性14例,女性17例,临床表现均为发热和浅表淋巴结肿大.所有的病例可见核碎片及淋巴细胞凋亡;淋巴结内出现片状或灶状形态多样的组织细胞增生.免疫组化标记CD45、CD68及CD3均为阳性表达.结论:本病病理形态以组织细胞增生为特征,主要是与组织细胞来源的淋巴瘤进行鉴别,免疫组化标记CD68及CD3阳性表达,对本病诊断有很重要的价值.该病属自限性疾病,预后多良好.     

Magnetic resonance imaging of cutaneous melanocytic lesions

This is the first literature report on magnetic resonance imaging (MRI) examination of cutaneous melanocytic or any other type of skin lesions. Good resolution, clinically useful MRI scans of a congenital nevus and a metastatic melanoma to the skin are presented. The potential usefulness of MRI technique to physicians dealing with cutaneous disease is discussed.     

Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions.

In vitro studies have demonstrated that fibronectin (FN) can deliver a mitogenic signal to quiescent human melanoma cells and that the alpha 5/beta 1-integrin receptor mediates this stimulus. In view of this finding we have analysed the in vivo expression of FN, and of ED-A and ED-B FN isoforms, in benign and malignant lesions of melanocyte origin. In the same specimens the expression of fibronectin integrin receptors was evaluated. The results demonstrate that, while detection of FN does not correlate with transformation and tumour progression, the expression of the two isoforms is associated with transformation and that only the ED-A variant is found in metastases. Integrin phenotyping disclosed that alpha 3/beta 1 expression is associated with tumour progression, alpha v/beta 3 is a marker of transformation, alpha 4 is rarely expressed and alpha 5 is expressed by about 50% and 30% of the primary and metastatic lesions respectively. Taken together, the results of this study demonstrate that transformation and tumour progression of the melanocyte lineage are associated with modulation of expression of FN isoforms and FN integrin receptors. Furthermore, the expression of alpha 5-integrin in a considerable percentage of primary and metastatic lesions indicates that FN may deliver a proliferative stimulus to melanoma cells in vivo.     

Clinicopathological features of Kaposi's sarcoma in Zaire

A total of 299 cases of Kaposi's sarcoma (KS) occurring in Zaire over a 21-year period have been reviewed in the Department of Pathology, Kinshasa University Hospital. Of these, 268 were localized in the skin (89,6%) with the majority (51.8%) in the lower limbs; 31 (10.4%) were located elsewhere, chiefly in the lymph nodes (71.0%). Adults were more severely affected (67.6%) than children (6.7%). The proportion of females (12.8%) was much less than that of males (79.6%) and the adjusted M:F ratio was 4.81:1. The highest frequency (24.7%) of KS was found in Equator Province. Only 1 KS-associated cancer was observed (0.3%). Histopathologically, angiomatous, granulomatous, sarcomatous and mixed types were encountered, with the last two predominating and accounting for 42.5% and 49.2%, respectively. KS accounted for 5.3% of all cancers registered in the Department over a 5-year period. This retrospective study of KS describes some major pathological and epidemiological features of the disease that may be of great importance in relation to further studies of acquired immunodeficiency syndrome (AIDS) in Zaire.     

Tyr-TGFalpha transgenic mice develop ocular melanocytic lesions

Transforming growth factor-alpha (TGFalpha) has been implicated in melanocyte transformation, as it is expressed in melanocytic lesions and in melanoma cells. We investigated its role in melanoma development using a transgenic mouse model. The mice were generated by microinjection of a transgene with 270 bp of the mouse tyrosinase promoter and the cDNA for human TGFalpha. No significant skin abnormalities were found, but individuals from three transgenic lines developed ocular melanocytoses (seven out of 10 transgenics), usually after a long latency period. In particular, the melanocyte component of the choroid was thicker than in non-transgenic controls, consistent with hyperplasia. The retinal pigment epithelium was unaffected. Melanocytic lesions were also present in the posterior eye, and abnormal distributions of melanocytes were found in neural tissue of the brain, skeletal muscle of the head and the Harderian glands, indicating migration from the choroid. It was concluded that mice engineered to express the normal growth factor TGFalpha from a tyrosinase promoter spontaneously developed melanocytic lesions in the eye but not the skin.     

Intraepidermal melanocytic proliferation. A practical guide to the classification of ambiguous melanotic skin lesions and of possible precursors of malignant melanomas

A group of senior Pathologists engaged in review work on international randomized trials for the W.H.O and/or the E.O.R.T.C., propose a new simplified classification of melanocytic lesions with an intra-epidermal component, applicable in routine. This classification attempts to introduce standards to permit morphological identification of a large group of intra-epidermal melanocytic proliferations with three classes of atypia (slight, mild, severe) and group of malignant melanomas especially those without dermal invasion. The new definitions and objective criteria (at cytological and architectural level) of diagnosis are given with examples of equivalence between some established entities and this new universal terminology.     

Clinicopathological features of primary gastric lymphoma

BACKGROUND AND OBJECTIVES: Surgery has been the mainstay of the treatment of primary gastric lymphoma, but the value of surgical treatment needs reevaluation. METHODS: Thirty-two patients with primary non-Hodgkin B-cell lymphoma of the stomach were examined retrospectively to evaluate prognostic factors and their impact on survival. All patients had undergone abdominal exploration for radical surgery between 1979 and 1992. The prognostic factors in view of survival after treatment were determined with both univariate and multivariate analyses. RESULTS: The resectability rate was 66% (21/32) and radical resections had been performed on 53% (17/32). The overall median survival was 65 months and the overall 5-year survival was 56%. The 5-year survival rates related to a modified Ann Arbor classification as follows: I 1E, 86%; I 2E, 100%; II 1E, 44%; II 2E, 37%; IIIE, 20%; and IVE, 0%. Univariate analysis using Kaplan-Meier estimates showed that radical surgery, Ann Arbor stage, patient's age, and lymph node involvement were significant prognostic factors. According to Cox proportional regression analysis, only Ann Arbor stage, radical surgery, and age were significant independent variables. CONCLUSIONS: According to our experience, surgery is still needed for the treatment of primary gastric lymphomas, but the benefits of primary chemotherapy or adjuvant chemotherapy using cytotoxic drugs must be determined in large prospective controlled trials.     

Clinicopathological features of human brainstem gliomas

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.     

Clinicopathological features of gastric stromal tumors

Stromal tumors in the gastrointestinal (GI) tract consist of myogenic tumors, neurogenic tumors and gastrointestinal stromal tumors (GISTs). Mutations in the c-kit gene have been found in GISTs, and GISTs with c-kit mutations showed aggressive clinical behavior and histological features. In the present study, we classified stromal tumors into four groups according to histological differentiation and c-kit mutation: myogenic tumors, neurogenic tumors, c-kit mutation (-) GISTs and c-kit mutation (+) GISTs, and examined their clinicopathological importance and validity using data obtained from 125 patients with gastric stromal tumors. There was no difference in preoperative symptoms and signs among the four groups. GISTs with c-kit mutations were large and showed invasion into neighboring structures compared with the other tumors, indicating the clinically aggressive features of mutation (+) GISTs. In histological examinations, c-kit mutation (+) GISTs were higher in cellularity (P < 0.0001) and mitotic cell count (P = 0.0086), and showed frequent histological necrosis (P = 0.0058) and hemorrhage (P = 0.0170), and consequently, were higher in histological grade (P = 0.0001). In prognostic analyses, overall, cause-specific and disease-free survival of patients in the mutation (+) GIST group was the poorest among the four groups. No significant differences were found among the other three groups of myogenic tumors, neurogenic tumors and c-kit mutation (-) GISTs, indicating a similar aggressiveness in clinical presentation and histological features. Thus, this classification is considered to be clinically and pathologically important in the diagnosis of gastric stromal tumors.