Clinicopathological, immunohistochemical and fluorescence in-situ hybridisation features of early subungual melanoma: an analysis of 65 cases.

AIMS: Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. METHODS AND RESULTS: Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. CONCLUSIONS: To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.

Establishment of Reference Intervals for Serum Cytokeratin-19 Fragment and Neuron Specific Enolase by Indirect Method Using Data Obtained from Healthy Chinese Population in Chengdu.

BACKGROUND: In order to establish suitable reference intervals (RIs) of serum cytokeratin-19 fragment (Cyfra211) and neuron specific enolase (NSE) for the healthy Chinese population in Chengdu, China, an indirect method was developed using the data from the people presented for routine health check-up. METHODS: All results for 4,988 healthy persons serum cytokeratin-19 fragment and 3,293 healthy persons neuron specific enolase were collected in our laboratory information system between January 2016 and December 2018. Outliers were identified and excluded using the stem-and-leaf and box plot methods. Mann-Whitney U test was used to observe the difference between sexes. Spearman's rank correlation analysis was used to evaluate the correlation between serum results and age. The RIs were defined by nonparametric 95th percentile interval. RESULTS: After statistical analysis the indirect RIs were 0.0 - 3.70 ng/mL (Cyfra211) and 0 - 17.26 ng/mL (NSE) in males and 0.0 - 3.35 ng/mL (Cyfra211) and 0.0 - 16.29 ng/mL (NSE) in females. Cyfra211 and NSE levels in males and females had no correlation with age. Therefore, there was no need to establish RIs according to age group. RIs of Cyfra211 and NSE were verified and passed the verification in the end. CONCLUSIONS: Using health check-up persons' laboratory data values is a relatively easy and cheap method of establishing laboratory specific references. This method deserves to be promoted and applied by other clinical laboratories.

Primary leiomyosarcoma of the fallopian tube: Three case reports and review of the literature.

OBJECTIVE: Leiomyosarcoma of the fallopian tube is a rare malignant gynecologic neoplasm with poor prognosis. It is important to share experience and to collect more cases to improve the understanding of the disease. CASE REPORT: We reported three patients with leiomyosarcoma of the fallopian tube who were treated in Fudan University Shanghai Cancer Center (Shanghai, China) from 2012 to 2016. Although the three cases shared the same diagnosis, they varied in the presentations, treatments, and outcomes. CONCLUSION: Leiomyosarcoma of the fallopian tube seems to have some particularities in imaging manifestations and immunohistochemical results. It has a progressive course with limited therapeutic options such as surgery, chemotherapy or radiotherapy.

Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease.

Chemokines are involved in many aspects of oncogenesis, including regulation of cancer cell growth, dissemination and host-tumor response. However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. High expression of CXCR7 also correlated with the depth of invasion. The prognostic value of these two chemokines were also investigated in progression-free survival (PFS) and cancer-specific survival (CSS). Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. In the multivariate analysis, depth of invasion, combined prognostic model and regional lymph node metastasis at diagnosis were the independent prognostic factors for EMPD patients for PFS, and the former two factors independently impacted CSS. Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD.

Syringocystadenocarcinoma papilliferum: Clinicopathologic analysis of 10 cases.

BACKGROUND: Syringocystadenocarcinoma papilliferum (SCACP) is an exceedingly rare cutaneous adnexal neoplasm. We aimed to investigate the clinicopathologic and immunophenotypic features of SCACP, and to discuss the prognosis of this rare entity. METHOD: We retrospectively collected clinical, pathological and follow-up data of 10 cases with SCACP. RESULTS: There were 8 males and 2 females, with ages ranging from 26 to 74 years. The chest was most frequently involved. Histologically, 1 case only showed SCACP in situ, 9 cases presented with variable invasive components of adenocarcinoma and/or squamous cell carcinoma in addition to areas of in situ. Apocrine differentiation with decapitation was evident in 4 cases and mucinous metaplasia was noted in 1 case. P63 was positive in invasive squamous cell carcinoma, while CK7 was variably positive in invasive adenocarcinoma. Regional lymph node metastasis was confirmed by pathological examination in 4 patients. Follow up was available for 9 patients, ranging from 3 to 112 months. Three patients died of the disease within 1 year after recurrences. CONCLUSIONS: Because of high rates of regional lymph node metastasis and mortality in our patients, clinical behavior of SCACP seems to be more aggressive than that previously reported.

Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases.

To investigate the clinicopathological and immunohistochemical features and prognostic factors for invasive extramammary Paget disease (EMPD) on penoscrotum, we described the clinical presentations, histopathology, and follow-up courses of 41 cases. The age of the patients ranged from 42 to 84 years. All the patients were treated with wide surgical excision, and 14 were confirmed to have lymph node metastasis. During follow-up, 18 patients (43.9%) developed local or distant recurrence, and 13 patients (31.7%) died of the disease. Histologically, glandular formation with true lumina within the epidermis was found in 29 cases, and signet ring cells were seen in 11 cases. In invasive components, nodular/micronodular growth pattern, glandular formation, and strands/solid sheets existed in 95.1% (39/41), 43.9% (18/41), and 24.4% (10/41) of the cases, respectively. More than half of the cases had at least 2 different types of invasive growth pattern. CK7 was diffusely positive in all cases, whereas CK20 was focally positive in 8 cases. GCDFP-15 was expressed to a variable degree in 24 cases. Presence of strands/solid sheets, lymphovascular invasion, and perineural invasion in invasive EMPD were found to be correlated with higher lymph node metastatic rate. Univariate analysis revealed that patients with one of the following prognostic factors: delay in diagnosis more than 7.5 years, depth of invasion more than 1 mm, invasive pattern of strands/solid sheets, marked inflammation, lymphovascular invasion, and lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Invasive pattern of strands/solid sheets is significantly associated with both lymph node metastasis and worse prognosis. Delay in diagnosis, depth of invasion, marked inflammation, lymphovascular invasion, and regional lymph node status are important prognostic factors.

Microcystic stromal tumour of the ovary: frequent mutations of ß-catenin (CTNNB1) in six cases.

AIMS: To analyse the clinicopathological, immunohistochemical and ß-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST). METHODS AND RESULTS: Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. ß-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T. CONCLUSIONS: MCST shows a unique morphology with characteristic immunophenotype. ß-catenin expression in the nucleus and ß-catenin mutations were identified in the majority of cases, which suggests that the Wnt/ß-catenin pathway may play a crucial role in the tumorigenesis of MCST.

Spiradenocarcinoma, cylindrocarcinoma and spiradenocylindrocarcinoma: a clinicopathological study of nine cases.

AIMS: To elucidate diagnostic criteria for spiradenocarcinoma, cylindrocarcinoma and spiradenocylindrocarcinoma, and to emphasize correlations between clinical behaviour and variable morphological patterns. METHODS AND RESULTS: We investigated the clinicopathological and immunophenotypic features of nine cases. There were five men and four women, with ages ranging from 58 years to 82 years. The tumour size varied from 10 mm to 50 mm. The head and neck were most commonly involved. Three cases of spiradenocarcinoma and three cases of cylindrocarcinoma showed a salivary gland-type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG) and/or high grade (BCAC-HG). The remaining three cases of spiradenocarcinoma showed adenocarcinoma in situ, with invasive adenocarcinoma being seen in one of these cases. PAS staining revealed loss of the PAS-positive hyaline sheath in malignant zones of cylindrocarcinoma. p53 staining was variably positive in the malignant components of all cases. Follow-up was available for all patients, ranging from 5 months to 107 months. Two patients died of disease, one experienced recurrence, and one died of an unrelated cause. CONCLUSIONS: Patients with BCAC-LG have a better prognosis. BCAC-HG is more likely to be found in cylindrocarcinoma, and its clinical behaviour seems to be more aggressive. Close follow-up for early detection of recurrence and metastases is strongly recommended.

MS4A8B promotes cell proliferation in prostate cancer.

BACKGROUND: Prostate cancer cells must maintain or achieve the further ability of proliferation during the progression. The molecular mechanisms, however, remain poorly understood. We identified a novel oncogene, termed membrane-spanning 4-domains, subfamily A, member 8B (MS4A8B), over-expressed in prostate cancer. METHODS: We firstly detected MS4A8B mRNA in 13 types of paired human normal and cancer tissues by real-time polymerase chain reaction (RT-PCR). In 140 clinically localized prostate cancer samples from radical prostatectomy, immunohistochemical staining was performed to study MS4A8B and PCNA protein level as an index of proliferative activity, TUNEL staining as an index of apoptosis. As MS4A8B RNAi and cDNA transfection technologies were used, the effect of MS4A8B on cellular vitality was determined in vitro and in vivo. RESULTS: MS4A8B mRNA was over-expressed specifically in prostate cancer. Positive ratios of MS4A8B protein expression were 1.94%, 5.92%, and 62.8% in benign, HPIN and prostate cancer, respectively. Moreover, MS4A8B was positively associated with Gleason score, the proliferation index. In vitro, MS4A8B knockdown resulted in G1 -S cell cycle arrest and descended vitality, MS4A8B over-expression with accelerated S phase entry, elevated vitality in prostate cancer cells. Moreover, it was also found that expression of MS4A8B led to changes of Cyclin D1 , Cyclin E1 and PCNA. LNCaP cells transfected with sh-MS4A8B lentivirus particles grew more slowly when subcutaneously injected into the flanks of nude mice. CONCLUSIONS: We conclude that the expression of MS4A8B expression promotes cell proliferation and plays an important role in carcinogenesis and progression of prostate cancer.

Analysis of KIT expression and gene mutation in human acral melanoma: with a comparison between primary tumors and corresponding metastases/recurrences.

KIT mutations play an important role during the pathogenesis of melanoma. Acral melanoma, which is the most common type in China, is more likely to harbor activating KIT mutations. Currently, there are few large studies on KIT expression and mutation in acral melanoma, especially in patients with matched primary/secondary pairs. Here, we investigated KIT expression and mutation in 39 primary acral melanomas together with their corresponding secondary tumors (17 lymph node metastases, 6 local recurrences, and 3 skin metastases) and explored the relationship between KIT expression, mutation, and clinicopathologic characteristics. Cytoplasmic and membranous staining for KIT was noted in 17 cases (43.6%) of 39 primary acral melanomas. KIT expression in patients without lymph node metastases at presentation was significantly higher than those with lymph node metastases (P = .024). KIT mutations were detected in 9 (23.1%) of 39 cases of primary acral melanomas. KIT expression did not correlate with KIT mutation status. In 23 cases with primary/secondary pairs, KIT mutations were observed in 6 cases. Comparison of KIT mutations between primary and secondary tumors showed a discordance rate of 13.0% (3/23). We concluded that KIT mutations are common in acral melanoma, and patients with acral melanoma should be screened for KIT mutations. Mutation status may change during metastases/recurrences after diagnosis of primary tumors. This has important clinical implications, and its mechanism needs further investigation.

[Cutaneous regressing/regressed malignant melanoma: a clinicopathologic analysis of 8 cases].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma. METHODS: Histopathologic evaluation and immunohistochemical study by EnVision method were performed in 8 cases of cutaneous regressing/regressed melanoma. The clinical presentation, treatment and follow-up data were analyzed. RESULTS: The age of the patients ranged from 40 to 69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1 case), and the forearm (1 case). Clinically, 6 patients presented with progressive black mole of the skin, followed by subsequent focal hypopigmentation, even scarring. Two patients presented with multiple foci of dark-brown pigmentation. Microscopically, 3 cases were completely regressed malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5 cases were melanoma with severe regression. The extent of regression ranged from 75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm. Immunohistochemically, both metastatic and primary tumor cells were diffusely positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68. Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five patients were alive with no evidence of disease, 1 patient was alive with stable disease and 2 patients died of metastatic melanoma. CONCLUSIONS: Correlation between clinical presentation and pathologic features is important for diagnosis of cutaneous regressing/regressed melanoma. Thin melanoma with extensive regression ( ≥ 75%) should not been regarded as low metastatic risk and wide excision combined with sentinel lymph node biopsy is recommended.

[Clinicopathologic study and immunohistochemistry comparison of Pax2, p53 and Ki-67 in low- and high-grade ovarian serous carcinomas].

OBJECTIVE: To evaluate the two-tier system for the grading of ovarian serous carcinomas, and to analyze Pax2, p53, Ki-67 protein expression and their prognostic values for low- and high-grade ovarian serous carcinomas. METHODS: A total of 38 cases of low-grade and 100 cases of high-grade ovarian serous carcinomas were selected based on the two-tier grading system. Immunohistochemistry was used to detect Pax2, p53 and Ki-67 protein expression in all cases. Correlation of the two-tier system with immunohistochemical results and prognostic parameters were performed. RESULTS: (1) The overall survival, disease-free survival and 5-year survival rates were significantly higher in the low-grade serous carcinoma cases than in the high-grade cases (P < 0.05). (2) Significant differences in protein expressions were found between the low- and high-grade serous carcinomas. The high-grade serous carcinomas had a significantly higher expression level of p53 (55.0% vs 13.2%, P < 0.05) and Ki-67 (42.1% vs 13.7%, P < 0.05), while low-grade carcinomas had a significantly higher expression level of Pax2 (65.8% vs 13.0%, P < 0.05). (3) Pax2 positive cases had a significantly better overall survival and 5-year survival rates than Pax2 negative cases (P < 0.05). The expressions of p53 and Ki-67 were found to have little correlation with overall survival and disease-free survival (P > 0.05). CONCLUSIONS: The two-tier system for the grading of ovarian serous carcinomas has a good prognostic value. There are significantly differences in expressions of Pax2, p53 and Ki-67 between low- and high-grade ovarian serous carcinomas. Compared with p53 and Ki-67, Pax2 is likely a better prognostic indicator for ovarian serous carcinoma.