Lily Ma

Small cell carcinoma of the esophagus

Ten cases of small cell carcinoma of the esophagus were studied clinicopathologically and immunohistochemically. Seven of the ten were also examined by electron microscopy. Histologically, six were oat cell type, four the intermediate cell type, and multiple histologic sections revealed squamous and glandular differentiations in small or minute areas of seven and two tumors, respectively. In four of the six polypoid tumors, the epithelium covering the tumor showed a malignant conversion accompanied by a proliferation of small anaplastic cells. Another one showed a cribriform pattern in a small area of the tumor. Argyrophilic tumor cells were seen in six cases and tumor cells immunohistochemically positive for ACTH and calcitonin were seen in six, and three cases, respectively. Neurosecretory granules were evident in three of the seven cases examined by electron microscopy. These findings suggest that a small cell carcinoma of the esophagus differentiates toward a squamous, glandular, or neurosecretory lesion, thereby supporting the idea of a totipotential stem cell origin of this tumor. The prognosis of patients with this tumor was poor, in accord with the evidence of aggressive lymphatic and blood vessel permeation.Background. Small cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent systemic dissemination.

Combined hepatocellular-cholangiocarcinoma: a clinicopathological study.

Combined hepatocellular‐cholangiocarcinoma (HCC‐CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin‐producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin‐negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α‐fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC‐CC were short. In conclusion, HCC‐CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.

Prognostic implication of proliferative markers MIB-1 and PC10 in esophageal squamous cell carcinoma.

Proliferative markers are related to tumor behavior. The commonly used markers are proliferating cell nuclear antigen (PCNA) and Ki‐67. The aim of this study is to evaluate the usefulness of MIB‐1 (for Ki‐67) and PC10 (for PCNA) in the assessment of the clinicopathologic features and prognosis in patients with esophageal squamous cell carcinoma.

Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas : A prospective clinico-pathological study and survival analysis of 70 patients

The tissues from 70 Chinese patients with oesophageal squamous cell carcinoma were prospectively collected to study for the pattern of p53 mutations and its relationship with clinico‐pathological features and prognosis using immunohistochemistry, polymerase chain reaction‐single strand conformational polymorphism (PCR‐SSCP) analysis and DNA sequencing. p53 over‐expression and p53 mutations were detected in 73% and 44% of the patients. These p53 aberrations had no relationship with the patient age, sex, smoking/drinking habits and tumor site, size or stage. The p53 over‐expression was more intense in moderately/poorly‐differentiated squamous cell carcinomas. Thirty‐three p53 mutations were noted in 31 patients; 18.2% in exon 5, 15.2% in exon 6, 33.3% in exon 7 and 33.3% in exon 8. Mutations were primarily point mutations and common in codons 248, 273 and 285. There were 46% transversions, 36% transitions and 18%; frameshift. The survival of the patients depended mainly on the extent of resection. In patients with stage III oesophageal cancer, the median survival of those with p53 mutations was 6.8 months whereas those without was 12.5 months. The results were of clinical importance although the value did not reach statistical significance. Thus, there was a definite role of p53 mutations in the pathogenesis of oesophageal squamous cell carcinomas. p53 mutations were not synonymous with p53 over‐expression. The distribution of p53 mutations in oesophageal cancers suggested that the etiologic contribution might be complex and probably involve different exogenous and endogenous exposures. p53 mutations also appear to play a role in predicting the survival of patients with stage III oesophageal squamous cell carcinomas. Int. J. Cancer 74:212‐219, 1997.

Prevalence of HPV infection in esophageal squamous cell carcinoma in Chinese patients and its relationship to the p53 gene mutation

Human papillomavirus (HPV), in particular types 16 and 18, is positively associated with anogenital cancers and may be an important etiologic factor in their pathogenesis. The goal of our study was to investigate the role of HPV infection in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and its relationship with the p53 mutation. We have examined ESCC collected from Sichuan, China, for the presence of HPV infection and p53 mutation. The presence of HPV DNA was detected by PCR‐Southern analysis while the p53 mutation was analyzed by PCR‐SSCP. High‐risk HPV (types 16 and 18) DNA was detected in 32 out of 152 cases of ESCC examined. In contrast, HPV DNA was not detected in normal esophageal tissues excised from the distant end (tumor free) of resected ESCC. Mutation of the p53 gene was detected in 22 out of 55 cases of ESCC. The distribution of the 22 p53 mutation was: 5 in exon 5, 1 in exon 6, 5 in exon 7, 10 in exon 8 and 1 in exon 10. The p53 mutation was detected at a significantly lower rate in ESCC with HPV infection. Our results support a role of HPV infection in the pathogenesis of ESCC from a high‐incidence area. Int. J. Cancer 72:959–964, 1997.

The pathological spectrum of desmoplastic infantile gangliogliomas.

A rare supratentorial neuroepithelial tumour in a 10‐month‐old girl is described. It was characterized by its voluminous size, a predominant leptomeningeal growth pattern with intense desmoplasia and divergent differentiation along astrocytic, neuronal and Schwann cell lines. The differential diagnoses are discussed with special reference to the recently described clinicopathological entity of desmoplastic infantile ganglioglioma.

Inflammatory cell-rich gastrointestinal autonomic nerve tumor. An expansion of its histologic spectrum.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon neoplasm of the gastrointestinal tract. Its histologic appearance is similar to other gastrointestinal stromal tumors. Ultrastructural demonstration of neural differentiation is required for its definitive diagnosis. Recently, we encountered two examples of GAN tumor that occurred in the body of the stomach and the cervical esophagus; the latter site has never been reported previously. These tumors showed unequivocal evidence of neural differentiation ultrastructurally, confirming the diagnosis of GAN tumor. Histologically, they were composed of swirling fascicles of spindle cells as well as a minor component of epithelioid cells, similar to that described previously. In addition, a cuff of lymphoid cells was noted at the peripheral part of both tumors and a scattering of mature plasma cells, lymphocytes, and foam cells was intermingled with the tumor cells. Such histologic features have not been described hitherto and can potentially be misinterpreted as features of inflammatory pseudotumor, inflammatory fibrosarcoma, or follicular dendritic cell tumor. There is a lack of CD34 expression in both tumors, but it would be premature to draw any conclusions about the potential usefulness of this observation.

Fatal Necrotizing Fasciitis due to Vibrio damsela

A patient who succumbed to fulminant necrotizing fasciitis due to Vibrio damsela after injury by a rabbitfish is described. Despite the absence of any known underlying illness, he did not respond to appropriate antibiotic therapy and radical surgical intervention. This represents the first documented case of necrotizing fasciitis due to this organism, and is also the first reported case in Southeast Asia inflicted by rabbitfish.

Angiosarcoma of the thyroid: an immunohistochemical and ultrastructural study of a case in a Chinese patient

A case of angiosarcoma (malignant hemangioendothelioma) developing in a chronic goitrous thyroid gland of an elderly Chinese woman is described. Histologically it showed the same classical appearance of angiosarcoma occurring in the skin and soft tissue. The endothelial origin of this tumor was confirmed by demonstrating Factor VIII‐related antigen in the neoplastic cells with the immunoperoxidase technique and Weibel‐Palade bodies by electron microscopic study. Because of its extreme rarity outside the European Alpine regions, many authorities are reluctant to accept it as a distinct entity and merely consider it as a variant of an undifferentiated carcinoma. Our report not only provides additional evidence that angiosarcoma of the thyroid gland is a specific condition of endothelial origin but also documents the first case among Chinese. Cancer 57:2381–2388, 1986.

Cytokeratin expression in non-neoplastic oesophageal epithelium and squamous cell carcinoma of the oesophagus.

The expression of cytokeratins (CK) 19, 8, 18, 13, 10 and 7 was examined in 35 cases of squamous cell carcinomas of the oesophagus (10 well-differentiated, 13 moderately-differentiated, and 12 poorly-differentiated) and the adjacent mucosa by means of a panel of monoclonal antibodies on frozen sections. The study was undertaken to assess the pattern of expression of these keratins in oesophageal tumours and its relation to the degree of differentiation. The normal oesophageal epithelia expressed CK19 in 86%, CK18 in 17% and CK13 in 14% of cases. CK8, CK10 and CK7 immunoreactivity was not observed. The tumours expressed CK19 in 86%, CK8 in 46%, CK18 in 97%, CK13 in 83%, CK10 in 34% and CK7 in 29% of cases. Thus, the so-called simple epithelial markers CK18 and CK19 occurred in the majority of oesophageal squamous cell carcinomas. CK13 (the so-called non-keratinizing squamous epithelial marker) was only infrequently demonstrated in the non-neoplastic oesophageal mucosa, and its expression was more frequent in carcinomas. CK10 was not demonstrated in non-neoplastic mucosa, but was mostly associated with well-differentiated carcinomas. We therefore conclude that the pattern of expression of cytokeratins in oesophageal carcinomas is different from that in normal oesophageal epithelia and varies with differentiation.