Papillary Squamous Cell Carcinoma of the Uterine Cervix: Report of a Case with HPV 16 DNA and Brief Review

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is a rare variant of squamous cell carcinoma (SCC). It is characterized by a papillary architecture and markedly atypical epithelium. Invasion and metastasis have been reported. We report a case of PSCC in a 72-year-old woman who subsequently tested positive for HPV 16. To our knowledge, this is the first report of HPV typing in a case of PSCC. Our finding of a high-risk HPV type in PSCC may help explain why PSCC has been reported to have a clinical course similar to that of nonpapillary SCC.     

Malignant potential of gigantic condylomatous lesions of the vulva.

A diagnostic and therapeutic approach in the identification of malignant lesions and the types of HPV in 11 patients with gigantic condylomatous vulvar protuberances is presented. Different histological types of squamous cell vulvar carcinoma have been found in 8 (72.7%) cases: condylomatous (4), verrucous (3) and basaloid type of the carcinoma (1). HPV type 16, confirmed in 5 cases, was most often present (4 condylomatous and 1 basaloid carcinoma types). Other types of HPV such as HPV-6 was detected in 3 cases of verrucous, type 11 in 2 cases of verrucous and condylomatous carcinoma and type 18 in 1 case of condylomatous carcinoma. Radical vulvectomy followed by bilateral inguinofemoral lymphadenectomy was performed in 4 patients with condylomatous carcinoma, hemivulvectomy in basaloid carcinoma whereas wide local excision was performed in the verrucous type of carcinoma. No patient died except 1 with condylomatous carcinoma in whom 6 positive lymph nodes were detected after the primary operation. The patient died 4 years later following 3 excisions of local recurrences.     

Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion

Abstract. Al-Nafussi AI, Monaghan H. Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion.
Invasive squamous carcinomas of the cervix have traditionally been classified into keratinizing, non-keratinizing, verrucous, warty (condylomatous), papillary transitional (squamo-transitional), and lymphoepithelioma-like carcinomas. The majority of these tumors are easily recognized. We present for the first time the pathological appearances of six cases of invasive squamous carcinoma with growth pattern simulating tangentially cut CIN 3 involving endocervical glandular crypts/clefts. In all cases initial diagnosis on biopsy and/or loop excision was thought to be CIN 3, perhaps with suspicion of early invasion. On further excision and/or on clinical grounds the tumors were frankly invasive. We propose the use of the term squamous carcinoma with "CIN 3-like growth pattern" for such lesions. This is in order to avoid misinterpretation as CIN 3 with subsequent inappropriate management of patients with this type of tumor.     

Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva.

Two distinct types of vulvar squamous cell carcinomas and their precursors, vulvar intraepithelial neoplasias (VIN), which differ in terms of clinical presentation and behavior, have been delineated. Human papillomavirus (HPV)-associated carcinomas are of basaloid or warty type, whereas tumors unrelated to HPV are usually keratinizing and differentiated. Thus, the major stratifying factor for vulvar carcinomas and VIN is their etiopathogenetic relationship with HPV. However, because of technical difficulties in confidently detecting HPV in tissues, this diagnosis is usually based on purely morphologic criteria, even though some overlap exists between these histologic types. Recently, the tumor suppressor protein p16 has been shown to be specifically overexpressed in HPV-related carcinomas and premalignant lesions of the uterine cervix, oral cavity, and anus, but the presence of p16 vulvar squamous lesions has not been examined. We have evaluated the immunohistochemical expression of p16 in a series of formalin-fixed, paraffin-embedded vulvar carcinomas and their putative precursors. p16 was strongly positive in all cases of basaloid/condylomatous VIN3 (30/30) and basaloid (7/7) and warty (3/3) carcinomas. In contrast, p16 was almost consistently negative in normal skin, squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated (simplex) VIN3 (0/11), verrucous carcinoma (0/2), and keratinizing squamous cell carcinoma (3/33, 9%). One of the keratinizing squamous cell carcinomas positive for p16 occurred in a 25-year-old woman and the other two were associated with small foci of basaloid VIN3 adjacent to the tumor, suggesting a probable relationship with HPV. p16 was positive in 6 of 10 of basal cell carcinomas. In conclusion, p16 immunostaining is a good discriminator between HPV-associated and HPV-unrelated vulvar carcinomas and VIN, although it cannot differentiate basaloid squamous and basal cell carcinoma.     

Papillary squamous cell carcinoma of the uterine cervix: a clinicopathologic study of nine cases

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is an infrequently described subtype of cervical malignancy. Nine cases of PSCC encountered at the University of Virginia Medical Center are reviewed. The clinical course of these patients, including a propensity for late metastases and recurrences, appears distinctive. The papillae of PSCC are lined by dysplastic cells, unlike verrucous carcinoma. PSCC may exist in an in situ state, and demonstration of invasion, when present, requires deep biopsies or cervical conization. Therapy for PSCC appears to be the same as for ordinary squamous cell carcinoma of equivalent clinical stage.     

Condylomas of the uterine cervix initially interpreted as squamous carcinoma: a report of four cases including a lesion resembling the Buschke-Loewenstein giant condyloma

The recognition of human papilloma virus (HPV)-induced cervicovaginal condylomatous lesions is in a period of dynamic development. It is estimated that condylomatous involvement of the uterine cervix is epidemic and that is particularly true in the younger, more sexually active woman. While cervical condylomas are often associated with cervical dysplasia, carcinoma in situ, or even invasive carcinoma, they are sometimes misdiagnosed as these entities. Four cases of cervical condylomas are presented that were clinically suspicious for malignancy and initially interpreted as squamous carcinomas on the basis of the histopathological findings.     

Mixed papillary transitional cell carcinoma and adenocarcinoma of the uterine cervix: a clinicopathologic study of three cases.

Although tumors consisting of a combination of transitional cell carcinoma (TCC) and adenocarcinoma have been described in the endometrium, they have not been documented in the uterine cervix to our knowledge. Three such cervical cases are reported in this article. Three patients, whose ages ranged from 40 to 61 years, presented with vaginal bleeding and malignant cells on routine Papanicolaou smears. The initial diagnoses based on a biopsy specimen were poorly differentiated squamous cell carcinoma in two patients and adenocarcinoma with a solid component in the third patient. All patients underwent radical hysterectomy. The hysterectomy specimens each contained a polypoid endocervical mass with minimal invasion of the cervical stroma. On microscopic examination, each tumor consisted of a component of papillary TCC admixed with an adenocarcinoma of endometrioid type. Both carcinomatous components were immunoreactive for cytokeratin (CK) 7 but not CK20. The three patients were alive and disease-free from 10 months to 4 years postoperatively. Recognition of this unusual variant of cervical carcinoma is important to delineate its clinical and pathologic features and establish prognostic differences, if any, from other histologic subtypes of cervical carcinoma. Papillary TCC mixed with adenocarcinoma broadens the morphologic spectrum of transitional cell neoplasms of the uterine cervix.     

Coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (HPV 31)

ObjectiveAdenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection.Case reportWe present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up.ConclusionA literature review revealed that this was a rare case of combined ABC–SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion.     

Verrucous squamous cell carcinoma of the female genital tract. Report of three cases and survey of the literature

Three new cases of gynecological verrucous squamous cell carcinomas are reported; one in the uterine cervix, and two in the vulva. The English literature covering the 49 cases reported previously is surveyed with special reference to the diagnostic and therapeutic aspects of these tumors, as well as with their clinical behavior and possible relationship to viral (HPV) lesions (Condylomas) of the genital tract.It was concluded that so far the exact relationship between the different verrucous squamous cell lesions in the genital tract remains obscure, all such lesions should be regarded as potentially malignant, and treated accordingly by radical surgery.     

Invasive condylomatous vulvar carcinoma associated with multifocal low genital tract neoplasia. A case report

Squamous cell carcinoma is a morphologically heterogenous neoplasm of specific histologic entities involved in human papillomavirus infection. The condylomatous types of squamous cell vulvar carcinoma, caused by HPV-16, most often manifest as exophytic papillary tumors mimicking condylomas.     

A case report: verrucous carcinoma of the endometrium--the difficulty of diagnosis, and a review of the literature

A verrucous carcinoma is a subtype of well-differentiated squamous-cell carcinomas, arising in the vagina, vulva, and uterine cervix. But a verrucous carcinoma very rarely arises in the uterine endometrium. The present paper presents a case of a verrucous carcinoma of the endometrium that is described in association with the tumor marker SCC; this paper also includes a review of the relevant literature.     

In situ hybridization study on the detection of HPV DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix]

Human papillomavirus (HPV) types 16 and 18 have been found closely associated with squamous cell carcinoma and related lesions of the uterine cervix. In order to investigate the relationship between HPV and adenocarcinoma and adenosquamous carcinoma of the uterine cervix, formalin-fixed, paraffinembedded tissues prepared from 38 cases consisting of 30 cases of adenocarcinoma and 8 cases of adenosquamous carcinoma were examined for the presence of HPV DNA by in situ hybridization with digoxigenin labeled HPV 6/11, 16, 18 DNA probes. HPV DNA was localized on the nuclei of the cancer cells in adenocarcinoma and adenosquamous carcinoma. HPV DNA was detected in 13 cases (43.3%) of adenocarcinoma and 4 cases (50.0%) of adenosquamous carcinoma, and HPV type 18 DNA was detected in 13 cases (34.2%) of adenocarcinoma and adenosquamous carcinoma. These findings suggest an association between HPV, especially HPV type 18, and adenocarcinoma and adenosquamous carcinoma of the uterine cervix.     

Morphological and immunohistochemical evidence of human papilloma virus (HPV) involvement in the dysplastic lesions of the uterine cervix

A series of 110 biopsies of the uterine cervix containing dysplastic and/or in situ changes were assessed morphologiccally with reference to presence or absence of the coexistent condylomatous lesions, and using the immunoperoxidase-PAP technique to disclose the HPV (human papilloma virus) antigens in the cells.Morphologically, 79 biopsies contained condylomatous (CO) lesions (63 flat, 12 inverted and 4 papillomatous ones), and 31 were non-condylomatous (NCO) dysplasias/ in situ carcinomas. The mean age of the CO group was more than 10 years less than that of NCO women (P < 0.0001). Of the papillomatous COs, 75% were associated with mild or moderate dysplasia only, whereas 42% of the inverted ones contained an associated in situ carcinoma. Most of the flat lesions were found in very young women (10–39 years of age).HPV antigens were demonstrated in all papillomatous lesions (100%), in 83% of the inverted ones, and in 67% of the flat COs. In generally, the frequency of the HPV-positive cases decreased when epithelial atypia increased. None of the NCO lesions showed HPV positive cells.The results support earlier morphological findings on the frequent association of cervical condylomas and epithelial dysplasias, as well as those on the HPV as the etiologic agent of the former. The role of HPV as a possible etiologic agent of the cervical squamous cell neoplasia deserves further attention.     

Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction.

A clinical, pathologic, and molecular virologic analysis of 30 cases of invasive squamous cell carcinoma of the vulva was undertaken to investigate the relationship of human papillomavirus (HPV) to this neoplasm. The presence of the virus was detected by the polymerase chain reaction and localized in the tumor and in the adjacent epithelium by in situ hybridization of paraffin sections of vulvectomy specimens. Specimens were examined for nucleic acid sequences of HPVs 6, 11, 16, and 18 were detected by in situ hybridization utilizing 35S-labeled antisense RNA probes and by polymerase chain reaction using HPV type-specific primers for a segment of the E6 gene followed by Southern hybridization of the amplified products. The cases were classified as typical squamous cell carcinoma, basaloid carcinoma, and warty carcinoma. Typical squamous cell carcinoma shows varying degrees of squamous maturation, whereas basaloid carcinoma is characterized by immature basal-type cells showing minimal or no squamous maturation. Warty carcinoma displays an exophytic condylomatous appearance. The squamous cells of this tumor are mature, and many show koilocytotic atypia characterized by a variable degree of nuclear atypia and cytoplasmic vacuolization. The adjacent epithelium was classified as squamous hyperplasia, lichen sclerosus, or vulvar intraepithelial neoplasia (VIN). VIN was subdivided into basaloid or warty VIN using similar criteria as for the invasive carcinomas. Overall, HPV 16 was detected in 11 cases and HPV 18 in two; none of the cases were positive for HPVs 6/11. HPV was detected in four (21%) of 19 squamous cell carcinomas, six (75%) of eight basaloid carcinomas, and three (100%) of three warty carcinomas. The adjacent epithelial lesions also showed a close correlation with the tumor type and presence of HPV. Fourteen (74%) squamous cell carcinomas had adjacent squamous hyperplasia; all of these squamous hyperplasias were negative for HPV. In contrast, seven (87%) of the basaloid carcinomas had adjacent basaloid-VIN and HPV 16 was detected within the VIN in three. Three warty carcinomas (100%) had adjacent warty VIN or basaloid VIN, and HPV was detected within VIN in two. The mean age of women with squamous cell carcinoma was 77 years, for women with basaloid carcinoma 54 years, and for those with warty carcinoma 47 years. The mean age of women with HPV-negative tumors was 77 years compared with 55 years for women with HPV-positive tumors (p less than 0.01). Thus, there appears to be a close correlation between the presence of HPV, specific subsets of invasive carcinoma and VIN, and age.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison between squamous cell carcinoma-associated antigen and CA-125 in patients with carcinoma of the cervix

Serum levels of CA-125 and squamous cell carcinoma-associated antigen (SCC) were measured in 30 patients with squamous cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenocarcinoma but in only 26% of patients with squamous cell carcinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical adenocarcinoma and confirm the value of the measurement of SCC antigen in patients with cervical squamous cell carcinoma. Moreover, we show that measurement of SCC antigen in adenocarcinoma and measurement of CA-125 in squamous cell carcinoma are of insufficient clinical value.     

HPV-associated verrucous carcinoma of the perianal region--complete remission after surgical excision and postoperative monochemotherapy with methotrexat

Verrucous carcinoma of the perianal area continues still to be rare finding, which in histopathological aspect is a highly differentiated form of squamous cell carcinoma. Many literature data show that it is quite possible that HPV viruses play probably a key role in the etiology of verrucous carcinoma. We present a case of 48 year-old female patient with verrucous carcinoma localized in the perianal area, treated initially under the diagnosis of perianal skin tags, while surgical removal of the lesion was found rare form of HPV associated verrucous carcinoma. A preventive mono-chemotherapy with methotrexate by scheme was started for an initial period of 3 months. Six months later, the provided monitoring has not shown clinical or apparative data on tumor recurrence. The article discusses key points of the diagnostic algorithm in patients with HPV associated lesions with anogenital localization and provides valuable recommendations for correct clinical behavior in these risk groups.     

Verrucous carcinoma of the uterine cervix: report of a case with follow-up of 6 1/2 years

A case of verrucous carcinoma of the uterine cervix was reported with a long-term follow-up and close observation. The patient was a 73-year-old, Japanese female, who had a suspicious Papanicolaou smear on routine examination. The cervix was replaced by a papillary mass, which was diagnosed as benign papilloma. The patient was followed every 6 months with cytology, colposcopy, and punch biopsy. No cytologic or microscopic diagnosis of invasive squamous cell carcinoma was made during the entire follow-up period. Total abdominal hysterectomy and partial vaginectomy were performed after 6 1/2 years' follow-up, and the tumor was finally diagnosed as verrucous carcinoma. The patient is alive and well 4 years after the operation.     

Human papilloma virus (HPV) antigens and DNA in dysplasia and carcinoma of the uterine cervix

Routinely paraffin-embedded sections of dysplasia, carcinoma in situ (CIS) and invasive (squamous) carcinoma of the cervix were studied to determine the participation of human papilloma virus (HPV) in these tissues. Morphological observation (1,059 cases) revealed condylomatous changes to reach 54% in dysplasia, 25% in CIS and 25% in invasive carcinoma. Condylomatous changes were also found to be 25 to 40% in the non-cancerous epithelia adjacent to in situ or invasive carcinomas. The immuno-peroxidase-PAP-method using anti-HPV serum was applied to 98 selected sections in which condylomatous changes were morphologically observed. HPV antigens were found to reach 56% in dysplasia, 42% in CIS and 35% in invasive carcinoma, and this result suggested that the morphologically observed condylomatous changes did not always coincide with virus maturation in the infected cells. By means of the in situ hybridization technique, HPV type-6, -11, -16 and -18 DNAs were all detected in dysplasia sections, whereas HPV type-16 DNA was demonstrated distinctively at a high rate among in situ and invasive carcinomas.     

Squamous cell carcinoma arising in a case of vulvitis granulomatosa or vulval variant of Melkersson-Rosenthal syndrome.

A case of vulvitis granulomatosa or the vulval variant of Melkersson-Rosenthal syndrome (MRS) in a young adult patient with systemic lupus erythematosus is presented. She also had evidence of cervicovulvovaginal human papilloma virus (HPV) infection. Nine years later she developed a squamous cell carcinoma (SCC) of the vulva. HPV 6/11 was found by DNA in situ hybridization within a vulval condyloma as well as within the carcinoma. This case is unusual in that SCC associated with HPV 6/11 developed in her vulva affected by MRS rather than in the cervix, where SCC was more likely to occur considering this patient's age.     

宫颈鳞癌中Cyclin E的表达和HPV16感染的相关研究

目的探讨Cyclin E在宫颈鳞状细胞癌中的表达及其与HPV16感染的关系.方法应用免疫组化S-P法对34例宫颈鳞状细胞癌组织进行Cyclin E与HPV16的检测,并与宫颈不典型增生和正常宫颈组织进行比较.结果正常宫颈组织无Cyclin E表达,宫颈不典型增生组织仅有少量袁达(11.11%),宫颈鳞状细胞癌有58.52%表达(P＜0.001),且与HPV16感染有明显相关性(P＜0.05).结论高危HPV感染是宫颈癌的重要病因,HPV感染通过多种途径改变了细胞的周期性调控,诱发细胞周期GI-S期检测点异常,引起细胞恶性增生,HPV感染与Cyclin E异常表达在宫颈癌的发生发展中起重要作用.