Huijiao Chen

Comparison of immunohistochemical markers in the differential diagnosis of adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors.

Most adrenocortical tumors (ACTs) can be diagnosed directly by a combination of morphologic features and clinical findings. However, sometimes it may be difficult to distinguish ACTs from other neoplasms such as pheochromocytomas and some metastatic tumors, particularly for small biopsy specimens because they may be morphologically similar. Expression of calretinin has recently been suggested as a valuable immunomarker for the differential diagnosis between ACTs and other tumors; however, its diagnostic value is still under debate. To determine the diagnostic value of calretinin in Chinese patients with adrenocortical and non-ACTs, we employed both polyclonal and monoclonal anticalretinin to characterize the expression of calretinin in adrenal tissues and compared its expression with that of inhibin α, Melan-A, cytokeratin, or CD99 by immunohistochemistry in tissue microarrays and standard tissue sections of 414 specimens. Our results revealed that calretinin was expressed by adrenocortical cells, but not by the other cells tested and the percentage of calretinin-positive ACTs reached 99% when stained with polyclonal antibodies, which was higher than that with monoclonal anticalretinin (91.3%), anti-Melan-A (90.3%), antiinhibin α (81.6%). In addition, our results also revealed that ACTs were stained by cytokeratin (AE1/AE3) with variable degrees (58.7%). Furthermore, unlike anti-Melan-A that stained all metastatic malignant melanoma, anticalretinin did not recognize other tested tumors. Therefore, immunohistologic staining with polyclonal anticalretinin is more sensitive than other antibodies tested for the diagnosis of ACTs. However, monoclonal anticalretinin appeared to be more specific. Importantly, our data suggested that the fried-egg–like staining pattern, but not the mere cytoplasmic staining, was characteristic of anticalretinin staining in adrenocortical tissues. Notably, a few anticalretinin negative-ACTs were stained by other immunomarkers that we tested. Thus, the combinational characterization of calretinin (either by polyclonal or monoclonal antibody), inhibin α, and Melan-A expression is of great significance in the differential diagnosis of ACTs.

Primary Monophasic Synovial Sarcoma of the Liver in a 13-Year-Old Boy

Synovial sarcoma originating in the liver is extremely rare, and thus far only 3 cases have been reported in the English literature. Herein, we report a primary hepatic synovial sarcoma in a 13-year-old Chinese boy. This patient present with a 10-day right upper quadrant pain, and a heterogeneous mass was documented in the right hepatic lobe by computed tomography. Subsequently, the patient underwent right hepatectomy. Histologically, the tumor exhibited classic features of monophasic synovial sarcoma. The diagnosis was confirmed by the presence of SS18 gene rearrangement and identification of SS18-SSX1 fusion transcript. Unfortunately, a relapsing mass was detected 11 months after the surgery. To the best of our knowledge, the current case is the 1st published example in the pediatric population.

Application of COL1A1–PDGFB fusion gene detection by fluorescence in situ hybridization in biopsy tissue of dermatofibrosarcoma protuberans

Several uncommon variants of dermatofibrosarcoma protuberans (DFSP) and the limitations of small biopsies render pathological diagnosis difficult. The aim of this study was to analyze the utility of fluorescence in situ hybridization (FISH) in the detection of the collagen type I‐α1/platelet derived growth factor‐β (COL1A1–PDGFB) fusion gene in biopsies of DFSP. Twenty‐three consecutive biopsy specimens of DFSP were reviewed for clinicopathological features and examined with the COL1A1–PDGFB fusion probe and PDGFB break‐apart probe using FISH analysis. The 23 tumor samples consisted of 11 males and 12 females (mean age at diagnosis, 37 years; range, 14–75 years). Eighteen conventional DFSP, one Bednar tumor, two myxoid DFSP and two fibrosarcomatous DFSP samples were included in the group. Strong and extensive CD34 expression was observed in 19 of 23 cases (83%). Twenty‐one cases (91%) were positive for both the COL1A1–PDGFB fusion signal and the PDGFB break‐apart signal. This is one of the few studies to demonstrate the value of FISH analysis of the COL1A1–PDGFB gene, which could validate complicated and suspected diagnoses in the routine biopsy of DFSP.

Concurrent primary angiosarcoma and invasive ductal carcinoma in the same breast

A 33-year-old Chinese female was admitted to a local hospital with a 20-day history of a painful lump in her right breast. Breast ultrasonography and mammography revealed a 2-cm irregular solid lesion in the breast. Previous exposure to radioactive or chemical substances and a history of extremity oedema were denied. A diagnosis of invasive carcinoma was made based on intraoperative frozen sections, and the patient underwent a right modified radical mastectomy in June 2009. A pathological examination revealed a high-grade invasive carcinoma with negative margins and axillary lymph nodes. The patient rejected postoperative adjuvant therapy. In February 2010 (8 months following the operation), the patient returned to the same hospital with a rapidly growing nodule at the original surgical site, measuring 1.5×0.8 cm. She subsequently underwent a lumpectomy, and a histological diagnosis of haemangioma was rendered. Unfortunately, a new mass measuring 1×0.8 cm emerged along the surgical scar 6 months later. The patient underwent a new lumpectomy with wider margins. Our department received the consultation slides from the peripheral hospital. Microscopy of the third lesion revealed an ill-defined tumour infiltrating the adipose tissue and dermis. The neoplasm was composed of predominantly solid areas with spindle cell morphology showing marked cytological atypia (figure 1 …

A novel sclerosing atypical lipomatous tumor/well-differentiated liposarcoma in a 7-year-old girl: report of a case with molecular confirmation

Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDL)/dedifferentiated liposarcoma (DDL) is a common type of liposarcoma in late adulthood. However, pediatric ALT/WDL/DDL is extremely rare, and only 3 cases have been described in children younger than 10 years of age. Notably, none of these cases harbored MDM2 gene amplification. Here, we reported a sclerosing ALT/WDL in a 7-year-old Chinese girl. Histologically, in most areas, the neoplastic cells were embedded within the collagenous background, and typical lipogenic areas were inconspicuous throughout the sclerotic areas. In addition, scattered small foci of atypical osseous/chondrous elements were identified. Notably, a small typical lipoma-like ALT/WDL area was detected in the periphery of the mass. Immunohistochemically, all the neoplastic components demonstrated positivity for MDM2, CDK4, and p16. Fluorescence in situ hybridization revealed MDM2 gene amplification in all the tumor components. To the best of our knowledge, this is the first example of MDM2-amplified ALT/WDL in this age group.

Whole exome and target sequencing identifies MAP2K5 as novel susceptibility gene for familial non-medullary thyroid carcinoma: MAP2K5 is a novel susceptibility gene for FNMTC

Although the genotype–phenotype for familial medullary thyroid carcinoma (FMTC) is well studied, only few low susceptibility risk loci were identified for familial non‐medullary thyroid carcinoma (FNMTC). The aim of this study is to screen and identify high‐penetrate genes for FNMTC. A total of 34 families with more than two first‐degree relatives diagnosed as papillary thyroid cancer without other familial syndrome were recruited. Whole exome and target gene sequencing were performed for candidate variants. These variants were screened and analyzed with ESP6500, ExAC, 1000 genomes project, and the Cancer Genome Atlas (TCGA) with SIFT score and Polyphen2 prediction. Finally, we identified recurrent genetic mutation of MAP2K5 variants c.G961A and c.T1100C (p. A321T and p.M367 T) as susceptibility loci for FNMTC. The frequencies of MAP2K5 c.G961A and c.T1100C were found, 0.0385 and 0.0259 in FNMTC and 0 and 0.00022523 in healthy Chinese controls (n = 2200, P < 0.001), respectively. Both variants were located in the protein kinase domain. The functional study showed that MAP2K5 A321T or M367 T could consistently phosphorylate downstream protein ERK5 on site Ser731 + Thr733 or Ser496, promoting nuclear translocation and subsequently altering target gene expressions. Our data revealed that MAP2K5 variants A321T or M367 T can activate MAP2K5–ERK5 pathway, alter downstream gene expression, and subsequently induce thyroid epithelial cell malignant transformation. While classic MAP2K1/2(MEK1/2)–ERK1/2 signaling is well known for driving sporadic NMTC, our research indicated that MAP2K5 (MEK5) is a susceptibility gene for FNMTC. These findings highlight the potential application of MAP2K5 for molecular diagnosis as well as early prevention.

Amplification of FRS2 in atypical lipomatous tumour/well‐differentiated liposarcoma and de‐differentiated liposarcoma: a clinicopathological and genetic study of 146 cases

The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well‐differentiated liposarcoma (WDL)/de‐differentiated liposarcoma (DDL).