BACKGROUND:Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy.METHODS:Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalinfixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome.RESULTS:High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis.CONCLUSIONS:High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.
Background Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast. Methods Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers. Results The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity. Conclusions These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.
© 2017 The Korean Society of Pathologists/The Korean Society for Cytopathology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. pISSN 2383-7837 eISSN 2383-7845 Human Papillomavirus Infection–Associated Adenoid Cystic Carcinoma of the Hard Palate
Microcystic meningioma is an unusual type of meningioma that has been described under various names including humid, myxomatous, vacuolated, or arachnoid trabecular cell meningioma.1 Histologically, microcystic meningiomas are characterized by numerous cystic spaces filled with edematous fluid and intermixed meningothelial cells of stellate or spider shape. Cytological descriptions of microcystic meningioma have been limited.2,3
Cystic Brunner’s gland hamartoma has been described under the various names including cystic hamartoma of Brunner’s glands, cystic Brunner’s gland heterotopia, Brunner’s gland cysts, Brunner’s gland cystadenoma, Brunner’s cyst, mucocele of Brunner’s glands, and cyst of Brunner’s glands. 1-4 Here, we report a rare case where a patient presented with an incidentally found, and long-standing pedunculated submucosal mass in the stomach body, which was diagnosed as a cystic Brunner’s gland hamartoma. To the best of our knowledge, no previous occurrence of cystic Brunner’s gland hamartoma in the
Fat-forming solitary fibrous tumor (SFT), previously known as lipomatous hemangiopericytoma, was described as an uncommon variant of extrapleural SFT in the 2013 World Health Organization (WHO) classification of soft tissue tumors.1 Fat-forming SFT is an uncommon, slow-growing neoplasm and is characterized by the typical histologic features of SFT with a mature adipocytic component. The fat-forming variant of SFT exhibits benign biological behavior; however, in rare case, it can have malignant histologic features. Fewer than 20 malignant cases have been reported in the English literature.2-5 Herein, we present a case of fat-forming SFT with malignant histologic features arising in the thigh, in addition to a review of the literature.
Alimentary tract duplications may occur from the oral cavity to the rectum. The ileocecal valve area is the most commonly affected site.1 Gastric duplication cysts are relatively rare congenital anomalies that constitute only 2% to 8% of alimentary tract duplications.2 These gastric duplication cysts are mostly discovered in children, with most patients presenting during the first year of their life. Associated symptoms often include nausea, vomiting, hematemesis, and abdominal pain.3 Ulceration, bleeding, rupture, and fistula formation are known complications. There have been a few case reports on gastric duplication cysts associated with malignancy.1,2,4,5 Previously reported malignant lesions have included adenocarcinoma, mixed adenocarcinoma and squamous cell carcinoma, and neuroendocrine carcinoma. Here, we report a case of adenocarcinoma arising in a gastric duplication cyst, the first such occurrence to be reported in Korean patients.
Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by fibroblast-like tumor cells, thick collagen bands, a hemangiopericytoma-like branching vascular pattern and CD34 expression of tumor cells.1 Although some cases show malignant behavior, most of the cases are benign and have histologically bland-looking tumor cells. Rarely, highly pleomorphic sarcoma arises within a primary or recurrent SFT having typical histologic features. This is a phenomenon similar to that seen in dedifferentiated liposarcoma. Dedifferentiated SFT (DSFT) is rare, with less than 30 cases reported worldwide,2,3,4,5,6 and it has not been previously reported in Korea. Here, we present a case of DSFT.
BACKGROUND:Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice.METHODS:To evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), β-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcription-PCR for β-actin (97 bp) were performed.RESULTS:All formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and β-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and β-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks.CONCLUSIONS:Fixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.
Papillary cystadenoma (PC) is an epithelial tumor believed to be of mesonephric origin[1] that is found rarely in the female genital tract. Since the original report by Gersell and King in 1988[2], only 14 cases have been reported in the English literature[1,3-5]. All of the reported cases occurred in the mesosalpinx or the broad ligament. Most of the tumors (12 out of 14) were associated with von Hippel-Lindau disease (VHL), similar to epididymal tumors[6]. We report a case of PC within the wall of the fallopian tube (rather than in the mesosalpinx or the broad ligament) in a patient with no clinical history of VHL. A comprehensive review of the literature with regard to differential diagnosis and immunohistochemical profile is provided.
Background Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. Methods Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). Results Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). Conclusions Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
BACKGROUND:Extensive evidence has accumulated regarding the role of mesenchymal stromal cells (MSCs) in tumor progression, but the exact effects and mechanisms underlying this role remain unclear. We investigated the effects of MSC-associated tumor progression in MSC-sarcoma models and a gastric cancer metastatic model.METHODS:We conducted an in vitro growth kinetics assay and an in vivo tumor progression assay for sarcoma cells and gastric cancer cells in the presence or absence of MSCs.RESULTS:MSC-cocultured human fibrosarcoma cells (HT1080) showed accelerated growth compared with HT1080 alone (79- vs 37-fold change, p<.050). For HT1080, human MSC-coinjected tumors showed significantly greater and highly infiltrative growth compared to those of HT1080 alone (p=.035). For mouse fibrosarcoma cells (WEHI164), mouse MSC-coinjected tumors had greater volume than those of WEHI164 alone (p=.141). For rat sarcoma cells (RR1022), rat MSC-coinjected tumors exhibited greater volume and infiltrative growth than those of RR1022 alone (p=.050). For human gastric cancer cells (5FU), tumors of 5FU alone were compact, nodular in shape, and expansile with good demarcation and no definite lung metastatic nodules, whereas tumors grown in the presence of human MSCs showed highly desmoplastic and infiltrative growth and multiple lung metastasis.CONCLUSIONS:We observed morphological evidence for MSC-associated tumor progression of fibrosarcomas and gastric cancer cells.
A seborrheic inclusion cyst (SIC) is a lesion, which has been described as a combination of seborrheic keratosis and an epidermoid cyst (EC). To the best of our knowledge, only eight cases of SIC have been reported thus far in the English literature[1-3]. Microscopically, SICs exhibit features that are suggestive of viral infection[4]. Therefore, an association between SICs and human papillomavirus (HPV) has been suspected, but it has only been demonstrated in one previous report by Terada,[1] which identified an HPV-positive SIC through immunohistochemical staining for HPV antigens. However, no SIC study has ever used HPV genotyping. Herein, we report the first case of SIC associated with HPV type 39, which we identified using the HPV DNA chip.
The presence of central nervous system (CNS) tissue outside the cranium is often referred to as although technically this should be termed ectopia, according to the dictionary definition. Glioneuronal heterotopia (GH) is a rare, mass-forming, malformative lesion. Ectopic glioneuronal tissue of the head and neck has been detected in the nasopharynx, oropharynx, tongue, palate, tonsils, soft tissue, eye, and orbit, and intracranial extracerebral glioneuronal heterotopia (IEGH) has also been reported, although less frequently.1,2 Since the first description of neuroglial heterotopia in the dorsal meninges of the cervical spinal cord by Wolbach in 1907,3 fewer than 20 cases of IEGH have been reported. Glioependymal cysts are rare, ependyma-lined, cystic lesions of the subarachnoid space, which have been referred to as epithelial or ependymal cysts. Histopathologically, they are lined with ependymal cells abutted on the glial layer and are commonly detected in the posterior fossa. The origin of glioependymal cysts of the posterior fossa is not clear, but these cysts may represent neuroglial heterotopia, persistent Blake's pouch (diverticulum of the roof of the fourth ventricle), or remnants of a tela chorioidea. We report here a case of IEGH that was predominantly composed of cerebellar tissue with some fat tissue and a large glioependymal cyst, and was initially misdiagnosed as a teratoma with a glioependymal cyst.
BACKGROUND:Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.METHODS:We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.RESULTS:The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.CONCLUSIONS:Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.
BACKGROUND:Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.METHODS:CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.RESULTS:High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.CONCLUSIONS:Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.
Follicular dendritic cell (FDC) sarcoma is rare and is classified either as conventional type or inflammatory pseudotumor (IPT)-like variant. Extranodal presentation is uncommon and nearly all gastrointestinal FDC tumors are of the conventional type. IPT-like variant tumors occur almost exclusively in the liver and spleen and are consistently associated with Epstein-Barr virus (EBV). Here we report the case of a 78-year-old woman with an IPT-like FDC sarcoma presenting as a pedunculated colonic polyp. Histologically, scanty atypical ovoid to spindle cells were mixed with a background of florid lymphoplasmacytic infiltrate, which led to an initial misdiagnosis of pseudolymphoma. These atypical cells expressed CD21, CD23, CD35, and D2-40, and were positive for EBV by in situ hybridization, confirming the diagnosis. The patient was free of disease five months after polypectomy without adjuvant therapy. Although extremely rare, the differential diagnosis for colonic polyp should include FDC sarcoma to avoid an erroneous diagnosis. A review of the 24 cases of IPT-like FDC sarcoma reported in the literature reveal that this tumor occurs predominantly in females with a predilection for liver and spleen, and has a strong association with EBV.
Although epithelioid blue nevus (EBN) is a rare variant of blue nevus that was first reported in patients with Carney complex, which encompasses cardiac and cutaneous myxomas, spotty skin pigmentation, endocrine overactivity, and psammomatous melanotic schwannomas [1], it has been also documented in the absence of such clinical features [2]. Histological characteristics of EBN are variably pigmented, large epithelioid melanocytes with vesicular nuclei and prominent eosinophilic nucleoli and a small number of melanophages that are sometimes associated with a few pigmented, spindle, and dendritic cells [3]. EBN is a diagnostically challenging entity because of its rarity and histological overlap with other pigmented melanocytic lesions, such as cellular blue nevus, malignant blue nevus, and the so-called animal-type malignant melanoma. Because it is very uncommon and no cases have been recorded in the Korean literature, this Korean case is reported.
Juvenile fibroadenoma is a rare variant of fibroadenoma ac counting for 4% of all fibroadenomas and characterized by rap id enlargement of single or multiple, painless, discrete masses,
Alveolar soft part sarcoma (ASPS) of the uterine cervix is a rare malignancy, and 21 cases have been reported the literature from every language (including our case).Herein, we describe a 17-yearold female patient who presented with active vaginal bleeding.Pelvic examination revealed a 1.6 × 1.0 × 0.5-cm-sized soft mass protruding from the uterine cervix.The final pathological diagnosis was ASPS of the uterine cervix.Immunohistochemically, tumor cells were strongly nuclear positive for transcription factor E3. The patient remained disease free for 24 months without adjuvant therapy.The prognosis of ASPS in the cervix is considerably better than that of ASPS in soft tissues due to early clinical detection, small size, and resectability.ASPS should be considered in the differential diagnosis of an unusual epithelioid neoplasm showing organoid appearance with mild cytologic atypia and no/rare mitotic figures, particularly in young women.Pathologists should be aware of those unusual locations where ASPS may originate.
