Well differentiated hepatocellular carcinoma: ddmPathological diagnosis of needle biopsied liver tissue

ope

Vimentin and Survivin Expression Rates as PrognosticFactors in Medulloblastoma

Background : A medulloblastoma is a primitive neuroepithelial tumor of the cerebellum that occurs in children and metastasizes through the cerebrospinal fluid. It is highly malignant and invasive, and the 5-year survival rate is only 60%. Surgical resection techniques, radiation, and chemotherapy have improved the overall survival but the patients suffer life-long cognitive dysfunctions or endocrine abnormalities as the side effects of treatment. Therefore it is essential to identify prognostic markers to determine the appropriate treatment strategy in order to minimize the side effects. Methods : This study evaluated the immunohistochemical differentiation and survival rate with synaptophysin, glial fibrillary acidic protein, epithelial membrane antigen, vimentin and primitive neuroepithelial marker nestin of 55 paraffin-embedded medulloblastomas, using a tissue microarray. The expression of survivin, the apoptotic inhibitor, and the survival rate with regard to the proliferation index of Ki-67 were also investigated. Results : The group testing positive to vimentin, a mesenchymal differentiation marker, had a worse prognosis and there was a strong correlation between vimentin expression and nestin expression. Patients with a survivin expression rate >35% had a significantly poorer clinical course and there was a correlation between the survivin expression rate and Ki-67 expression rate. Conclusion : In conclusion, vimentin and survivin are negative prognostic markers in medulloblastomas.ope

Chondrosarcoma of the Head and Neck

Chondrosarcoma of the head and neck region is a rare disease, representing approximately 0.1% of all head and neck neoplasms. The 5-year survival rate of chondrosarcoma is 70-80%, showing relatively good prognosis; however, it is known to progress slowly and eventually cause multiple metastases. In this study, we reviewed chondrosarcoma cases experienced at Yonsei University Medical College during the last 15 years to investigate its clinical characteristics and treatment outcome. The medical records of 8 patients who were diagnosed with chondrosarcoma of the head and neck region and underwent surgical treatment between December 1990 and December 2002 were retrospectively reviewed. The primary sites were sinus, mastoid, jugular foramen and thyroid cartilage. In all patients, the initial treatment modality was surgery, and postoperative radiation therapy was performed in 4 cases. The pathological findings showed chondrosarcoma in 7 cases and mesenchymal chondrosarcoma in 1 case. The treatment outcome resulted in 3 cases of recurrence, of which 2 cases were treated successfully and the other case expired of disease, indicating a survival rate of 87.5%. In the case that resulted in death, complete excision could not be achieved. Therefore, we concluded that wide excision is a beneficial initial treatment of this rare disease.ope

Two cases of Vessel invasion of Hepatocellular carcinoma

Despite growing information on the clinical behavior of hepatocellular carcinoma(HCC), the histologic features associated with survival are not well characterized. Several different staging systems are suggested for use in predicting the prognosis of HCC. American Joint Committee on Cancer/International Union Against Cancer Staging System (AJCC/UICC) 6th edition divided T stages according to vessel invasion, T1 without microvessel invasion, T2 showing microvessel invasion and T3 showing major vessel invasion. The vessel invasion is generally considered a poor prognostic factor for HCC. Our report of the two patients with HCC run along similar terms. The patient diagnosed HCC with microvessel invasion underwent left lateral sectionectomy. Although the presence of microvessel invasion was found, this patient has survived without any recurrence for over 5 years now. The other patient underwent S8 segmentectomy and lived 10 years disease-free. After 10 years, although an intrahepatic recurred HCC successfully treated with local therapy, the recurred and newly developed multiple lesions were found again leading to a decision to perform operation. The HCC invaded into the portal vein and constituted portal vein thrombosis. The patient expired after 3 months postoperatively due to intrahepatic dissemination of the tumor. Therefore the impact of the vascular invasion on long-term survivors remains to be determined.ope

A case of hepatocellular carcinoma misdiagnosed as an adrenal incidentaloma

Adrenal incidentalomas are adrenal masses discovered incidentally at the time of imaging procedures performed for nonadrenal problems. Since the early 1980s, incidentally discovered adrenal masses have become a common clinical problem as a result of the more idespread use of high resolution imaging procedures such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography. However, several conditions, called pseudoadrenal masses, can be occasionally misdiagnosed as an adrenal mass. Pseudoadrenal masses are usually located at the left side, but we have experienced a right-side pseudoadrenal mass. We report a patient with a hepatocellular carcinoma simulating a right adrenal mass. To our knowledge, this is extremely rare and the first case reported in Korea. It was possible to make a final diagnosis only after ultrasound-guided liver biopsy.ope

경화성 간세포암종에서 간줄기세포 표지자, 전환성장인자 베타신호 체계, 상피간엽전환 관련 유전자 발현

의과학과/박사[한글]최근 암줄기세포가 암종의 불량한 예후 및 치료 저항성에 관여하며, 상피간엽전환 (epithelial mesenchymal transition)이 암줄기세포의 발생을 촉진함이 보고되었다. 또한 상피간엽전환은 종양세포의 혈관 침입 및 전이에 중요하며, 전환성장인자 베타 (transforming growth factor-β, TGF-β)가 상피간엽전환에 중요한 유전자로 알려져 있다. 전형적인 간세포암종은 섬유성 간질조직의 형성이 거의 없는 것이 특징이고, 종양세포 사이에 섬유성 간질의 형성이 풍부한 조직학적 소견을 보이는 경우 경화성 간세포암종이라 하며, 그 임상병리학적 의의는 아직 확실히 알려져 있지 않다. 본 연구에서는 경화성 간세포암종의 병리학적 특성을 밝히고자, 수술전 치료없이 절제된 경화성 간세포암종 19예를 대상으로 임상병리학적 소견, 간줄기세포 표지자 [EpCAM, CD133, keratin 19 (K19), K7, CD56, alpha-fetoprotein (AFP)], 간세포분화 표지자 (Hep Par 1), TGF-β 신호 물질(TGF-β, TGF-β Receptor I, TGF-β Receptor II, Smad4)과 상피간엽전환 관련 유전자 (Snail, Twist)의 발현을 실시간 역전사 중합효소연쇄반응 및 면역조직화학 염색으로 검색하여 전형적인 간세포암종 (24예)과 비교 검색하였다. 경화성 간세포암종은 전형적인 간세포암종에 비하여 섬유성 간질조직 형성 (p<0.0001), 종양세포의 미세혈관 침범 (p=0.004) 및 문맥혈관침범 (p=0.047), 간내 전이 (p=0.044)가 의의있게 높았으며, 종양피막의 형성 (p<0.0001)은 더 낮았다. 간줄기세포 표지자 (EpCAM, K19, K7, CD56, AFP)에 대한 최근 암줄기세포가 암종의 불량한 예후 및 치료 저항성에 관여하며, 상피간엽전환 (epithelial mesenchymal transition)이 암줄기세포의 발생을 촉진함이 보고되었다. 또한 상피간엽전환은 종양세포의 혈관 침입 및 전이에 중요하며, 전환성장인자 베타 (transforming growth factor-β, TGF-β)가 상피간엽전환에 중요한 유전자로 알려져 있다. 전형적인 간세포암종은 섬유성 간질조직의 형성이 거의 없는 것이 특징이고, 종양세포 사이에 섬유성 간질의 형성이 풍부한 조직학적 소견을 보이는 경우 경화성 간세포암종이라 하며, 그 임상병리학적 의의는 아직 확실히 알려져 있지 않다. 본 연구에서는 경화성 간세포암종의 병리학적 특성을 밝히고자, 수술전 치료없이 절제된 경화성 간세포암종 19예를 대상으로 임상병리학적 소견, 간줄기세포 표지자 [EpCAM, CD133, keratin 19 (K19), K7, CD56, alpha-fetoprotein (AFP)], 간세포분화 표지자 (Hep Par 1), TGF-β 신호 물질(TGF-β, TGF-β Receptor I, TGF-β Receptor II, Smad4)과 상피간엽전환 관련 유전자 (Snail, Twist)의 발현을 실시간 역전사 중합효소연쇄반응 및 면역조직화학 염색으로 검색하여 전형적인 간세포암종 (24예)과 비교 검색하였다. 경화성 간세포암종은 전형적인 간세포암종에 비하여 섬유성 간질조직 형성 (p<0.0001), 종양세포의 미세혈관 침범 (p=0.004) 및 문맥혈관침범 (p=0.047), 간내 전이 (p=0.044)가 의의있게 높았으며, 종양피막의 형성 (p<0.0001)은 더 낮았다. 간줄기세포 표지자 (EpCAM, K19, K7, CD56, AFP)에 대한 면역염색 결과 경화성 간세포암종의 26.3~94.7% 및 전형적인 간세암종의 4.2~50%에서 양성발현을 보여, 경화성 간세포암종에서 간줄기세포 표지자의 발현이 의의 있게 높았다 (p<0.05). 또한 경화성 간세포암종에서는 EpCAM, K19, CD133, Oct3/4, cMET의 mRNA발현이 전형적인 간세포암종에 비하여 의의있게 높았다 (p<0.05). 반면 간세포 분화의 표지자인 Hep Par 1는 경화성 간세포암종에서 68.4%, 전형적인 간세포암종에서 100% 발현되어, 경화성 간세포암종에서 더 낮게 발현되었다 (p<0.05). TGF-β 신호 물질 (TGF-β, TGF-β Receptor I, TGF-β Receptor II, Smad4) 및 상피간엽전환 관련 유전자 (Snail, Twist)의 mRNA발현은 모두 경화성 간세포암종에서 전형적인 간세포암종 보다 의의 있는 증가를 보였다 (p<0.05). 이중면역조직화학염색으로 간줄기세포 표지자와 Snail의 발현양상을 검색하였다. 간줄기세포 표지자는 섬유성 간질과 맞닿은 종양세포 군집의 변연부에서 발현하는 경향을 보였으며, 대부분의 경우 (69%)에서 상피간엽전환의 핵심 인자인 Snail과 함께 발현되었다. 환자의 추적관찰 결과 경화성 간암종은 전형적인 간세포암종에 비하여 의의있게 높은 재발율을 보였다 (P=0.030). 이상의 소견으로 경화성 간세포암종은 간줄기세포 표지자의 발현, 상피간엽전환 및 TGF-β 신호의 발현증가로 침습적인 병리생물학적 특성 및 불량한 예후를 보이는 것으로 생각되며, 이러한 특성을 근거로 경화성 간세포암종은 단순히 간세포암종의 조직학적 소견의 하나가 아니라, 간세포암종의 특징적인 아형으로 분류하는 것이 좋을 것으로 생각한다. [영문]Recently cancer stem cell has been reported to be involved in the chemo-resistance and poor prognosis of cancer patients. Epithelial mesenchymal transition (EMT), which is important in vascular invasion and metastasis of cancer, has been reported to induce cancer stem cell and a fibrogenic cytokine transforming growth factor-β (TGF-β) has been reported to induce EMT during tumorigenesis. Scirrhous hepatocellular carcinoma (HCC) is characterized by abundant fibrous stroma between tumor trabeculae, whereas the fibrous stroma is usually very little in classical HCC. Scirrhous HCC has been considered as one of histological patterns of HCC and its clinicopathological significance remains unclear. In this study, we selected 19 cases of resected scirrhous HCC (>60% of fibrous stroma of tumor volume) without pre-operative treatment and 24 cases of classical HCCs as a control group. The clinicopathological features, the expression of liver stem/progenitor cell markers [epithelial cell adhesion molecule (EpCAM), keratin (K) 19, K7, CD56, CD133, Oct3/4, cMET and alpha fetoprotein (AFP)], hepatocyte marker (Hep Par 1), TGF-β signal pathway [TGF-β, TGF-β receptor I (TGFβRI), TGF-β receptor II (TGFβRII) and Smad4], and EMT-related genes (Snail and Twist) were investigated in scirrhous HCCs and classical HCCs by real time quantitative PCR and immunohistochemical stain and compared between two groups.Scirrhous HCCs showed significantly higher incidence of microvascular invasion (p=0.004), portal vein invasion (p=0.047) and intrahepatic metastasis (p=0.044), and significantly lower incidence of tumor capsule formation (p<0.0001) compared to classical HCCs. The incidence of positive expression of liver stem/progenitor cell markers (EpCAM, K19, K7, CD56, and AFP), detected by immunohistochemical stain, was 26.3~94.7% in scirrhous HCCs in contrast to 4.2~50% in classical HCCs, and the mRNA levels of EpCAM, K19, CD133, Oct3/4, and cMET were significantly up-regulated in scirrhous HCCs than in classical HCCs (p<0.05). The expression rate of hepatocyte marker (Hep Par 1) was low in scirrhous HCCs (68.4%) compared to classical HCCs (100%) (p<0.05). The mRNA levels of TGF-β signal pathway (TGF-β, TGFβRI, TGFβRII, Smad4) and EMT related genes (Snail and Twist) were significantly up-regulated in scirrhous HCCs compared to classical HCCs (p<0.05). The tophographical expression pattern of liver stem/progenitor cell markers (EpCAM and K19) and Snail was evaluated by double immunohistochemical stain. The expression of liver stem/progenitor cell markers was mainly detected in the periphery of tumor cell nests, facing the fibrous stroma and most of them (69%) showed co-expression of Snail. The tumor recurrence was significantly higher in scirrhous HCCs (52.6%) than in classical HCCs (20.8%) during the mean follow up of 18 months (p=0.030). In conclusion, scirrhous HCC is suggested to be a distinctive subtype showing invasive and aggressive clinicopathological characteristics, in which EMT, up-regulated TGF-β pathway and induction of liver stem/progenitor cell markers are involved.ope

Vimentin, nestin and survivin expression rates as prognostic factors in medulloblastoma

의학과/석사[한글]수모세포종은 주로 소아의 소뇌에서 발생하는 악성, 침윤성 배아 종양으로, 뇌척수액을 따라 전이하며, 5년 생존율이 60% 에 불과하다. 수술적 절제, 방사선 치료와 항암 치료를 병행하여 이전에 비해 생존율이 높아졌지만, 치료에 의한 후유증은 발달이 진행중인 소아 환자에게는 치명적인 경우가 많다. 따라서 수모세포종의 적절한 치료를 위한 정확한 예후 예측 인자를 찾는 것은 매우 의미 있는 일이다.이번 연구에서는 tissue microarray를 이용하여 수모세포종의 분화형을 synaptophysin, glial fibrillary acidic protein, epithelial membrane antigen, vimentin의 면역조직화학적 염색을 이용하여 살펴보고, 이와 신경상피 전구세포에서 발현되는 nestin과의 관계를 검색하여 수모세포종의 예후와의 관계를 살펴보았다. 또한 기존에 수모세포종의 예후 인자로 알려진 세포자멸사와 관련하여, 세포의 증식능을 나타내는 Ki-67과 세포자멸사의 억제 단백 물질인 survivin의 표현율의 상호 관계와 수모세포종의 예후에 미치는 영향을 분석하였다.분석 결과, 중배엽 분화를 나타내는 vimentin과 nestin의 발현이 상관 관계가 있었고, Ki-67이 표현율이 높을수록 survivin의 표현율도 높았다. Vimentin은 수모세포종의 나쁜 예후 인자이고, Ki-67표현율이 50% 이상인 경우와 survivin표현율이 35% 이상인 경우도 나쁜 예후 인자로 나타났다. 결론적으로 vimentin과 survivin은 수모세포종의 나쁜 예후 인자이다. [영문]Medulloblastomas are a primitive neuroepithelial tumor of the cerebellum in children and metastasize via the cerebrospinal fluid. It is highly malignant and invasive that the 5-year survival rate is just 60%. The treatment modality have improved overall survival rate, but patients suffer from various side effects such as cognitive dysfuction or endocrine abnormalities. It is essential to uncover the prognostic marker for treatment strategy to minimize side effects.We evaluated the immunohistochemical differentiation and survival rate with synaptophysin, glial fibrilary acidic protein, epithelial membrane antigen and primitive neuroepithelial marker nestin in 55 paraffin-embedded medulloblastoma tumors, using tissue microarray. We also investigated the expression of survivin, the apoptotic inhibitor, and change in survival rate with regard to the proliferative index of Ki-67.We found the vimentin, mesenchymal differentiation marker, positive group shows a high correlation with a worse prognosis and is statistically associated with nestin expression. Patients with a survivin expression rate of over 35% show a statistically worse clinical course with a high correlation with the expression rate of Ki-67. In conclusion, vimentin and survivin are negative prognostic markers in medulloblastomas.ope

Cytologic features of metastatic lymphoepithelial carcinoma in pleural fluid: a case report

BACKGROUND: Lymphoepithelial carcinoma of the salivary gland is a rare undifferentiated or poorly differentiated squamous cell carcinoma associated with abundant inmphocytes. Only a handful of reports descibe the cytologic features of fine needle aspiration in lymphoepithelial carcinoma of the salivary gland and lymph nodes. CASE: A 29-year-old man presented with a painless mass in his right parotid gland. After the surgical specimen was evaluated, the mass was diagnosed as a lymphoepithelial carcinoma, which extended to the periglandular soft tissue with lymph node metastasis. Despite radiation and chemotherapy, multiple mediastinal lymph node metastases, including in the right hilar lymph nodes, occurred. Pulmonary atelectasis of the right upper lobe and a right pleural effusion developed. Aspiration cytology of metastatic lymph nodes and pleural effusion cytology both demonstrated strongly cohesive clusters of tumor cells. These cells had vesicular nuclei and prominent nucleoli admixed with benign lymphoid cells. CONCLUSION: Pleural effusion cytopathology ofmetastatic lymphoepithelial carcinoma is similar to that of primary tumor fine needle aspiration. Therefore, a specific diagnosis of lymphoepithelial carcinoma is possible on the basis of body fluid with these cytologic featuresope

The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma

BACKGROUND/AIMS: Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC. METHODS: We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (n=13), low-grade dysplastic nodules (n=21), high-grade dysplastic nodules (n=50), very well-differentiated (VWD) (n=17), well-differentiated (WD-G1) (n=40) and G2-3 (n=35) HCC. RESULTS: Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity. CONCLUSIONS: This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human modelsope

Image of the month : Multicentric Hepatocellular Carcinomas and Multiple Dysplastic Nodules -Spectrum of Nodular Lesions in Hepatitis B-viral Cirrhotic Liver

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