CYTOPATHOLOGY

New cervical cancer screening strategy: Combined Pap and HPV testing

Xian Wen Jin, Kristine Zanotti, Belinda Yen-Lieberman

The strategy for cervical cancer screening is being revolutionized by the new understanding of how human papillomavirus (HPV) contributes to carcinogenesis and the natural history of cervical cancer. The American Cancer Society and the American College of Obstetricians and Gynecologists now recommend combined HPV and Papanicolaou (Pap) testing for cervical cancer screening in women age 30 or older. However, although incorporation of HPV DNA testing into primary screening provides clear benefits, it also raises new questions.

HPV infection most often is transient in younger women. With increasing age, the likelihood increases that HPV positivity represents persistent disease, and only those who have persistent high-risk HPV infection are at risk of cervical cancer.

Combined HPV DNA testing and Pap testing is now recommended for primary screening in women age 30 or older. If both tests are negative, the screening interval can be extended to every 3 years.

If a woman has a positive result on HPV testing but a negative result on Pap testing, she should repeat both tests in 6 to 12 months.

Eventually, the search for ideal cervical cancer biomarkers will improve risk stratification in screening, while an HPV vaccine will eradicate cervical cancer.

Cleveland Clinic Journal Of Medicine 72, Number 2, February 2005

 

Cytologic findings of cervicovaginal smears in women with uterine papillary serous carcinoma

Park JY, Kim HS, Hong SR, Chun YK.

The goal of this study was to evaluate the cytomorphologic features of histologically confirmed uterine papillary serous carcinomas (UPSC) of the endometrium. Authors reviewed cervicovaginal smears from 12 patients with UPSC who had done their cervical smears at six months to a year earlier before the time of diagnosis; nine smears (75%) were diagnosed as positive for malignancy and three smears (25%) were diagnosed as negative. The cervical smears of patients with UPSC revealed frequent papillary clusters that were composed of large pleomorphic tumor cells with prominent nucleoli in a background of necrosis. Other findings revealed from the tests were relatively frequent single malignant cells and bare nuclei. Although the Pap smear is not a sensitive screening test for endometrial carcinoma, authors could depend on it to reveal the cytologic features of UPSC which are fairly characteristic and reliable for a preoperative diagnosis of UPSC. Preoperative identification of this poor prognostic variant of endometrial carcinoma may influence the surgical management of these cases and the choice of adjuvant therapy.

J Korean Med Sci. 2005 Feb;20(1):93-7.

 

 

ANATOMIC PATHOLOGY

India has some of the highest cancer rates in the world

 Ganapati Mudur

Parts of India have the world's highest incidence of cancers of the gall bladder, mouth, and lower pharynx, India's first cancer atlas shows.

The atlas, produced by the Indian Council of Medical Research, has also found pockets of stomach and thyroid cancer in the south of the country.

The National Cancer Registry Programme in Bangalore used data from 105 hospitals and private clinics in 82 of the 593 districts in India to map the incidence of cancer, as part of a project funded by the World Health Organization.

The survey included more than 200 000 patients with histopathologically confirmed cancers, whose details were sent to the registry through the internet.

Previously, the registry, which was launched in 1981, had covered just a few cities and a single village and had relied on hospital records and death certificates to estimate the burden of cancer. It used to take up to five years to submit the information. Data analysis for the atlas took just 15 months.

The atlas, scheduled for release by the health ministry within the next few weeks, indicates that the age adjusted incidence of gall bladder cancer in women in New Delhi is 10.6 per 100 000 of the populationthe world's highest rate for women for this cancer.

Districts in central, south, and northeast India had the world's highest incidence of cancers associated with tobacco, which is chewed as well as smoked in India. Aizawl district in the northeastern state of Mizoram has the world's highest incidence of cancers in men of the lower pharynx (11.5 per 100 000 people) and tongue (7.6 per 100 000 people), the atlas shows. The district also has the country's highest rate of stomach cancer among men.

The incidence of mouth cancer among men in Pondicherry was 8.9 per 100 000, one of the highest rates in the world for men. Rates of stomach cancer were high among men in Bangalore and Chennai.

"These findings will give us a better picture of realities [on the ground] and help [us to make] wiser resource allocation," said Dr Purvish Parikh, head of medical oncology at the Tata Memorial Hospital in Mumbai. Cancer epidemiologists have long been concerned that diagnostic services for cancer are inadequate in many parts of India.

The survey also detected "a belt of thyroid cancer" in women in coastal districts of Kerala, Karnataka, and Goa. The findings are expected to stimulate research to identify risk factors at specific locations.

"[Lower] pharynx cancer may be linked to tobacco use, but we're going to explore the genetic components of stomach cancer," said Dr Eric Zomawia, pathologist at the Government Hospital in Aizawl and collaborator on the project.

The incidence atlas also confirmed earlier observations that breast cancer has replaced cervical cancer as the leading site of cancer among women in Indian cities and that lung cancer is the most common cancer in men in Calcutta, Mumbai, and New Delhi.

BMJ 2005;330:215 (29 January), doi:10.1136/bmj.330.7485.215-c

 

Putative Precursors of Gallbladder Dysplasia: A Review of 400 Routinely Resected Specimens

Sanjay Mukhopadhyay, MD; Steve K. Landas, MD

Despite increasing interest during the past few decades, the precise relationship between gallbladder cancer and its precursors remains nebulous. In other organs, well-defined entities such as cervical intraepithelial neoplasia and prostatic intraepithelial neoplasia have been delineated, and a well-defined progression from low-grade to high-grade lesions is widely accepted. Although previously proposed, such a sequence of progression for gallbladder carcinoma is neither clearly defined nor widely appreciated.

 ContextDysplasia is thought to be a precursor of invasive gallbladder carcinoma, but it is unsettled whether dysplasia arises from other precursor lesions.

ObjectiveTo ascertain the presence and nature of precursors of dysplasia in the gallbladder.

DesignFour hundred consecutive cholecystectomy specimens were processed and stained routinely for diagnosis. Authors retrospectively reviewed these cases to look for the presence of epithelial changes, including antral-type metaplasia, intestinal metaplasia, and dysplasia.

ResultsAntral-type metaplasia, intestinal metaplasia, and dysplasia were found in 238 (59.5%), 39 (9.8%), and 20 (5.0%) cases, respectively. The mean patient age was 47.7 years (range, 1593 years). The mean ages for patients with antral-type metaplasia, intestinal metaplasia, and dysplasia were 49.4, 50.9, and 52.6 years, respectively. Statistically significant associations were found between antral-type metaplasia and intestinal metaplasia (P = .007, χ² test) and between intestinal metaplasia and dysplasia (P < .001, χ² test).

These associations, along with the age gradient from antral-type metaplasia to dysplasia, suggest a progression from antral-type metaplasia to dysplasia via intestinal metaplasia.

In summary, authors have described the precursors of gallbladder dysplasia using histologic examination of a large number of routinely resected cases from a North American population. The results are in agreement with earlier data (based on studies involving Japanese and Latin American populations) that dysplasia is strongly associated with intestinal metaplasia, which in turn is associated with antral-type metaplasia. These associations are supported by an age gradient, with younger patients at the benign end of the sequence (antral-type metaplasia) and older patients at the dysplastic end. Other investigators have substantiated the proposed relatedness of these epithelial changes with carcinoma at a molecular level. If future studies are able to demonstrate accrual of molecular abnormalities correlating with the statistically substantiated morphologic sequence demonstrated herein, considerable evidence would be added in support of such precursor lesions.

Archives of Pathology and Laboratory Medicine: 129, No. 3, pp. 386390, 2005

 

 

Current practice of Gleason grading among genitourinary pathologists
Egevad L, Allsbrook WC, Epstein JI.

There is consensus that the Gleason system should be used for grading of prostate cancer. However, a number of controversial issues remain as regards how this grading is applied. A questionnaire was sent to 91 genitourinary pathologists in countries around the world with the purpose to survey current practice of Gleason grading. The response rate was 74%, including 43 North American pathologists and 24 from other continents. Of all participants, only 13% and 36%, respectively, ever diagnosed a Gleason score (GS) of 2 to 3 or 4 on needle biopsies (NBX), and 88% of those who did so assigned a GS 4 to <1% of cancers. Cribriform Gleason pattern (GP) 3 was acknowledged by 88% but a majority of them would classify </=20% of cribriform patterns as GP 3. One third only accepted cribriform or fusion patterns as GP 4, but two thirds also included incomplete or poorly defined glands. For GP 5 to be identified on NBX, 83% required clusters of individual cells, strands, or nests seen at less than x40 lens magnification. Only 26% defined GS on NBX as primary + tertiary GP, and a majority would mention a tertiary pattern separately. For NBX, global or highest GS was reported by 40% and 10%, respectively, whereas 46% only gave a separate GS for each individual NBX core. In conclusion, there is a need to standardize practical application of Gleason grading both in terms of interpretation of patterns as well as how grading is reported. authors survey data provide information to general pathologists about the most common grading practices among genitourinary pathologists.

 Hum Pathol. 36(1):5-9,2005

 

 Pathological study of distal mesorectal cancer spread to determine a proper distal resection margin

Zhao GP, Zhou ZG, Lei WZ et al

AIM: Local recurrence after curative surgical resection for rectal cancer remains a major problem. Several studies have shown that incomplete removal of cancer deposits in the distal mesorectum contributes a great share to this dismal result. Clinicopathologic examination of distal mesorectum in lower rectal cancer was performed in the present study to assess the incidence and extent of distal mesorectal spread and to determine an optimal distal resection margin in sphincter-saving procedure. METHODS: Authors prospectively examined sepecimens from 45 patients with lower rectal cancer who underwent curative surgery. Large-mount sections were performed to microscopically observe the distal mesorectal spread and to measure the extent of distal spread. Tissue shrinkage ratio was also considered. Patients with involvement in the distal mesorectum were compared with those without involvement with regard to clinicopathologic features. RESULTS: Mesorectal cancer spread was observed in 21 patients (46.7%), 8 of them (17.8%) had distal mesorectal spread. Overall, distal intramural and/or mesorectal spreads were observed in 10 patients (22.2%) and the maximum extent of distal spread in situ was 12 mm and 36 mm respectively. Eight patients with distal mesorectal spread showed a significantly higher rate of lymph node metastasis compared with the other 37 patients without distal mesorectal spread (P = 0.043). CONCLUSION: Distal mesorectal spread invariably occurs in advanced rectal cancer and has a significant relationship with lymph node metastasis. Distal resection margin of 1.5 cm for the rectal wall and 4 cm for the distal mesorectum is proper to those patients who are arranged to receive operation with a curative sphincter-saving procedure for lower rectal cancer.

World J Gastroenterol. 21;11(3):319-22, 2005

 

 

Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up

Miettinen M, Sobin LH, Lasota J.

Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. In this study, authors analyzed 1869 cases originally classified as smooth muscle tumors of the stomach and found that 1765 (94%) of these were GISTs. The GISTs had a slight male predominance (55%) with a median age of 63 years. Only 2.7% of tumors occurred before the age of 21 years and 9.1% before the age of 40 years. The tumors varied from 0.5 to 44 cm (median, 6.0 cm) and most commonly presented with GI bleeding; 12% were incidentally detected. Several histologic variants were recognized among the spindle cell tumors (sclerosing, palisaded-vacuolated, hypercellular, and sarcomatous) and of epithelioid tumors (sclerosing, dyscohesive, hypercellular, and sarcomatous). Outcome was strongly dependent on tumor size and mitotic activity. Only 2% to 3% of tumors <10 cm and <5 mitoses/50 HPFs metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPFs metastasized. However, tumors >10 cm with mitotic activity <5/50 HPFs and those <5 cm with mitoses >5/50 HPFs had a relatively low metastatic rate (11% and 15%). A small number of patients survived intra-abdominal metastasis up to over 20 years. Tumor location in fundus or gastroesophageal junction, coagulative necrosis, ulceration, and mucosal invasion were unfavorable factors (P <0.001), whereas tumor location in antrum was favorable (P <0.001). KIT expression was detected in 91% of the cases, CD34 in 82%, smooth muscle actin in 18%, and desmin in 5%; the latter two were favorable (P <0.001). KIT exon 11 mutations were detected in 119 cases; patients with point mutations fared better than those with deletions (P <0.01). PDGFRA exon 18 mutations (total 86 cases) were common in epithelioid GISTs and most commonly represented a D842V point mutation; none of these was prognostically significant. The above results may be helpful for setting the criteria for adjuvant treatment such as Gleevec.

 Am J Surg Pathol. 29(1):52-68,2005

 

 

Pathogenesis of carcinoma of the papilla of Vater

Fischer HP, Zhou H.

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.

 J Hepatobiliary Pancreat Surg 11(5):301-9,2004

 

 

Immunohistochemical analysis of SOX6 expression in human brain tumors

Ueda R, Yoshida K, Kawakami Y et al

Authors previously demonstrated that the developmentally regulated gene, SOX6, is strongly expressed in glioma cells and in the fetal brain, but only faintly in the normal adult brain. Recent studies have indicated that brain tumor cells may share antigens, signaling systems, and behavior with neural stem/progenitor cells. To test the validity of this proposition, authors analyzed the expression of SOX6 in various human central nervous system (CNS) tumors. Immunohistochemical analysis revealed that astrocytic and oligodendroglial tumors expressed SOX6; neuronal-glial cell tumors (central neurocytoma) and embryonal tumors (medulloblastoma), which arise from multipotential stem cell precursors, also showed a high intensity of SOX6 staining. In contrast, ependymal tumors (ependymoma and subependymoma), meningioma, and schwannoma, which are all well differentiated tumors, showed either no staining or only faint staining for SOX6. These results suggest that SOX6 may be expressed in bipotential or multipotential cells capable of neuronal and glial differentiation, but not in fully differentiated cells. SOX6 may be a useful marker for the diagnosis of tumors arising from immature bipotential cells that may differentiate into neuronal and glial cells.

 

Brain Tumor Pathol. 21(3):117-20 ,2004