OBJECTIVETo further understand the clinicopathological, ultrastructural and molecular features of penile pseudoangiosarcomatous squamous cell carcinoma (PASCC), and improve its diagnosis and treatment.

METHODSA 47-year-old male patient with penile PASCC was reported and the relevant literature reviewed. The main clinical manifestations of the patient were a typical surface ulceration with hemorrhage and purulent secretion with a foul smell, a papillary mass about 5.0 cm x 5.0 cm x 4.0 cm for 1 year on the foreskin of the penis, and 3 enlarged bilateral inguinal lymph nodes. CT scanning showed no enlarged lymph nodes in the abdomen and pelvis, and X-ray examination revealed no abnormality in the chest.

RESULTSThe diagnosis was established by biopsy. Partial penectomy and bilateral inguinal lymphadenectomy (T2N2M0) were performed, followed by adjuvant pelvic radiotherapy. Two months later, total penectomy was necessitated by penile flap necrosis and local recurrence. Eleven months after the first surgery, the patient died of extensive metastasis to the pelvis and lungs. Under the light microsope, the tumor was mainly composed of vessel-like lacunar reticularis spindle cells and a few local squamous cancer cells. Careful examination revealed some focal areas with evident transition from squamous nests to the more acantholytic areas extending towards the pseudoangiosarcomatous spaces. Pathogenetically, it appeared to be the variant of acantholytic squamous cell carcinoma. Immunohistochemically, most tumor cells were strongly positive for keratin (AE1/AE3) and focally positive for EMA, with the typical squamous cells focally positive for 34betaE12 and vimentin. The vessels that proliferated in the tumor were decorated by CD31, CD34 and factor VIII-related antigens, but the tumor cells were negative for HMB45, SMA, Desmin and CEA. HPV DNA (HPVpan, HPV6B/11, HPV16/18, HPV31/33) was not detected by in situ hybridization in the primary and metastatic tumors.

CONCLUSIONPASCC is a specific and extremely rare subtype of penile SCC with dramatic similarity to angiosarcoma under the microscope, with poor prognosis. Its diagnosis depends on histopathological, immunohistochemical and ultrastructural studies. Such a presentation underscores the importance of timely consultation, early diagnosis and prompt treatment.

Carcinoma, Squamous Cell ; pathology ; virology ; Humans ; Male ; Middle Aged ; Papillomaviridae ; isolation & purification ; Penile Neoplasms ; pathology ; virology ; Penis ; pathology ; virology

Carcinoma in Situ ; pathology ; virology ; Carcinoma, Squamous Cell ; pathology ; virology ; Diagnosis, Differential ; Female ; Humans ; Paget Disease, Extramammary ; pathology ; virology ; Papillomavirus Infections ; Precancerous Conditions ; pathology ; virology ; Vulvar Neoplasms ; classification ; pathology ; virology ; Warts ; pathology ; virology

Human papillomavirus (HPV) is a major causative agent of head and neck squamous cell carcinomas (HNSCC). Over the past several decades, an increasing number of studies established the strong association of HPV with the invasion and metastasis of HNSCC. In the present study, we reviewed the gene mutations in HPV-associated HNSCC and the unique mechanism of E6- and E7-mediated carcinogenesis via interactions with an array of cellular elements. We further discussed the progress in the mechanisms of invasion and metastasis; these mechanisms include non-coding RNAs, deregulating cellular energetics, tumor microenvironment, cancer stem cells, angiogenesis, and lymphangiogenesis.
Head and Neck Neoplasms ; pathology ; virology ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Papillomaviridae ; Papillomavirus Infections ; Squamous Cell Carcinoma of Head and Neck ; pathology ; virology

Warty squamous cell carcinoma (WSCC), a rare variant of squamous cell carcinoma occurring in younger women, is primarily associated with human papillomavirus (HPV) infection. Although WSCC appears to exhibit less aggressive behavior than typical well-differentiated squamous cell carcinoma, it bears the risk of regional metastasis. Accordingly, WSCC should be differentiated from other verruciform neoplasms. We describe a rare case of WSCC with a short disease duration occurring in a woman of old age. We found the presence of HPV DNA different from other well-known types of high risk and low risk HPV by DNA chip microarray. These results suggest that various types of HPV can be associated with the pathogenesis of WSCC.
Aged ; Carcinoma, Squamous Cell/pathology/*virology ; Female ; Humans ; Papillomavirus Infections/*complications/pathology ; *Papillomavirus, Human ; Skin Neoplasms/pathology/*virology ; Vulvar Neoplasms/pathology/*virology

OBJECTIVETo establish a human laryngeal carcinoma cell line unassociated with human papillomavirus (HPV).

METHODSViable tissue of a well-differentiated laryngeal squamous cell carcinoma was obtained and tested negative for the presence of HPV by polymerase chain reaction. Minced tissue fragments were then transplanted subcutaneously into nude mice. After two successive passages, the tumor tissue was seeded into culture flasks and incubated in a medium containing 10% fetal bovine serum, insulin and epidermal growth factor. Tumor cell phenotype and molecular features were determined by various methods.

RESULTSA stable cell line, designated as Lscc-02, was successfully established after 86 culture passages. The cells grew as a monolayer with epithelioid features. The cell doubling time was approximately 39.1 hours. The human origin of the tumor cells was confirmed by karyotype analysis. The squamous epithelial phenotype was demonstrated by the immunopositivity of anti-cytokeratin antibodies and ultrastructural presence of tonofilaments and desmosomes. The malignant nature of the cells was documented by their clonal formation in soft-agar and tumorigenicity in nude mice. Lscc-02 cells expressed carcinoembryonic antigen (CEA) and were negative for HPV DNA.

CONCLUSIONThis newly established Lscc-02 laryngeal squamous cell carcinoma cell line may be a useful model for investigating laryngeal carcinoma unrelated to HPV infection, and the role of HPV in the progression of human laryngeal carcinoma.

Animals ; Carcinoma, Squamous Cell ; pathology ; virology ; Cell Line, Tumor ; Humans ; Laryngeal Neoplasms ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Papillomaviridae

OBJECTIVETo examine and follow up cervical cytology of pregnant and postpartum women and study their cytopathologic characteristics, so as to determine screening and managing programs for abnormal cervical cytology.

METHODSTotally 5296 patients in pregnancy and postpartum, in which 3729 by computer-assisted cytology test and 1567 by liquid-based monolayers cytology test, were examined and diagnosed by the Bethesda System made in 2001. Those proven epithelial abnormalities patients were followed up until the lesions regressed to normal. The remaining patients, who exhibited persistent abnormalities or progression, were given further examinations.

RESULTSThe positive rate of cervical cytological test was 8.72% (462/5296), including squamous carcinoma (SCA) 1 case (0.02%), high grade squamous intraepithelial lesion (HSIL) 34 cases (0.64%), low grade squamous intraepithelial lesion (LSIL) 145 cases (2.74%), atypical glandular cells (AGC) 5 cases (0.09%), atypical squamous cells cannot exclude HSIL (ASC-H) 14 cases (0.26%), atypical squamous cells of undetermined significance (ASC-US) 263 cases (4.97%). The 419 proven cytological abnormality cases were followed up successfully. The total transnegative rate in three months was 73.74% (309/419), in which 303 cases (72.32%) persisted normal status for more than six months after regression. And the transnegative rate of ASC-US, ASC-H, AGC, LSIL, and HSIL were 79.56%, 64.29%, 100%, 72.14% and 44.12%, respectively. Forty-six cases received biopsy directed by colposcopy. The distribution of coincidence of cytopathologic and histopathologic diagnosis was: SCA 1 case (100%), HSIL 10 cases (76.92%), LSIL 13 cases (65%), ASC-H 2 cases (50%), ASC-US 3 cases (37.50%), total 29 cases (63.04%).

CONCLUSIONSWe should cast more attention to screening cervix lesions in pregnant and postpartum women. Their cytopathologic characteristics are liable to make the clinician give a false positive diagnosis. So we propose to follow up them closely and to lower the indication of biopsy.

Adult ; Biopsy ; Carcinoma, Squamous Cell ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; pathology ; virology ; Female ; Follow-Up Studies ; Humans ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; Postpartum Period ; Precancerous Conditions ; pathology ; virology ; Pregnancy ; Uterine Cervical Neoplasms ; pathology ; virology ; Vaginal Smears

OBJECTIVETo detect the high-risk human papillomavirus (HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade squamous intraepithelial lesion.

METHODSWe used hybrid capture 2 (hc2) method to examine 949 patients with abnormal cervical cytology results [ > or =atypical squamous cells of undetermined significance (ASC-US) according to the 2001 The Bethesda System diagnosis criteria]. All subjects also received colposcopy for tissue studies.

RESULTSAmong 949 patients with abnormal cytology, the diagnoses of atypical squamous cells (ASC), low grade squamous intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion (HSIL) were made in 432, 310, and 207 patients, respectively. The high-risk HPV positive rate in ASC, LSIL, and HSIL were 40.3%, 44.8%, and 89.4%, respectively. The numbers of patients with pathologically confirmed results of negative intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia 1, 2, 3 (CIN 1, 2, 3), and squamous cell carcinoma (SCC) were 335, 388, 118, 101, and 7, and the high-risk HPV positive rate was 17.3%, 66.2%, 92.4%, 97.0%, and 100%, respectively. Among patients with atypical squamous cells of undetermined significance (ASC-US), rate of HSIL in high-risk HPV positive group and negative group were 10.2% and 0.8%, respectively (P < 0.01). In screening HSIL, the sensitivities of cytology [ > or = ASC cannot exclude HSIL (ASC-H)] and cytology ( > or = ASC-H) plus high-risk HPV testing were 0.925 and 0.991, and the specificities were 0.510 and 0.748, respectively (P < 0.01). Sensitivitives of cytology ( > or = LSIL) and cytology (> or = LSIL) plus high risk HPV in detecting HSIL were 0.898 and 0.982, respectively, while the specificitives were 0. 567 and 0.779, respectively (P < 0.01).

CONCLUSIONSThe positive rate of high-risk HPV increases with the gravity of cervical lesions. In patients with abnormal cervical cytology, high-risk HPV testing can improve the sensitivity and specificity in the screening of HSIL.

Carcinoma, Squamous Cell ; diagnosis ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; virology ; Female ; Humans ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; pathology ; virology ; Risk Assessment ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; virology

The pathogenesis of endocervical glandular lesions are not clearly understood. The aims of this study are to evaluate the etiologic role of human papillomavirus (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB-1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7% and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD and low grade EGD, respectively. P53 protein expression rates of malignant glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%, respectively. High MIB-1 labelling index was found in 73.7% of malignant glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD, respectively. There were statistically significant differences in HPV 16/18, p53 and MIB-1 expressions between malignant endocervical glandular lesions and EGD, but no significant difference in p53 and MIB-1 expressions in relation to HPV 16/18 expression. In malignant endocervical glandular lesions, HPV 16/18 infection may be a major causative factor, but not be related to p53 and MIB-1 expressions.
Adenocarcinoma/pathology/physiopathology/*virology ; Carcinoma, Squamous Cell/pathology/physiopathology/virology ; Cervix Neoplasms/pathology/physiopathology/*virology ; Female ; Human ; Nuclear Proteins/analysis/*genetics ; Oncogene Proteins, Viral/genetics ; *Papillomavirus, Human ; Papovaviridae Infections/*pathology/physiopathology ; Protein p53/analysis/*genetics ; Tumor Virus Infections/*pathology/physiopathology

OBJECTIVETo evaluate the correlation of the expression of homeodomain-interacting protein kinase 2 (HIPK2) with human papillomavirus (HPV) infection and apoptosis in cervical cancer.

METHODSFormalin-fixed, paraffin embedded tissue samples from 50 cervical cancers and 15 normal uterine cervix cases were obtained. Apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay and the expression of HIPK2 as well as HPV by immunohistochemical staining.

RESULTSHIPK2 protein expression was detected in 88.0% (44/50) of cervical cancers and 6.7% (1/15) of normal cervical tissues. HPV was found in 78.0% (39/50) of cervical cancers and 20.0% (3/15) of normal cervical tissue samples. The expression of HIPK2 protein was significantly and positively correlated with HPV presence (r=0.467, P<0.01), but negatively with apoptotic index (r=-0.370, P<0.05).

CONCLUSIONHIPK2 protein expression is positively correlated with HPV infection, but negatively with apoptotic index in cervical cancers. Therefore, HIPK2 may be involved in the mechanism of apoptosis in cervical cancer and may play an important role in cervical carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Carrier Proteins ; metabolism ; Cervix Uteri ; metabolism ; Female ; Humans ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

OBJECTIVETo study the expression of Skp2 in cervical squamous cell carcinoma (SCC) and its precancerous lesions, and to investigate its relationship with human papillomavirus (HPV) infection.

METHODSThe expression of Skp2 protein and HPV16/18 DNA was determined using immunohistochemistry and in-situ hybridization in 30 cases of normal cervical squamous epithelium, 29 cases of low-grade intraepithelial neoplasia, 31 cases of high-grade intraepithelial neoplasia and 31 cases of cervical SCC.

RESULTSSkp2 expression was not detected in normal cervical squamous epithelium and no significant difference was obtained statistically on Skp2 expression between normal cervical squamous epithelium and low-grade intraepithelial neoplasia (P > 0.05). However, the expression of Skp2 gradually increased with elevation of epithelial lesion grading in an order from low to high grade and to cervical SCC (P < 0.01). The positive rate of HPV16/18 DNA in cases of normal cervical squamous epithelium, low-grade, high-grade intraepithelial neoplasia and cervical SCC was significantly different (P < 0.01), although both high-grade intraepithelial neoplasia and cervical SCC had a similar high HPV infection rate up to 96.8%. There was no correlation obtained between Skp2 expression and HPV16/18 infection in low-grade intraepithelial neoplasia. In contrast, expression of Skp2 and HPV infection were significantly correlated in both high-grade intraepithelial neoplasia and cervical SCC (gammaH = 0.373, gammaC = 0.416, P < 0.05).

CONCLUSIONSAbnormal expression of Skp2 is present mainly in high-grade cervical intraepithelial neoplasia and invasive carcinoma, which may be considered as a surrogate marker for the high-grade lesions. Skp2 may play a key role in the development of cervical squamous carcinoma induced by HPV16/18 infection, through E7-Skp2-Rb signaling pathway.

Carcinoma ; pathology ; virology ; Carcinoma, Squamous Cell ; etiology ; virology ; Cervical Intraepithelial Neoplasia ; Female ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Immunohistochemistry ; Papillomaviridae ; Papillomavirus Infections ; complications ; Uterine Cervical Neoplasms ; pathology ; virology