Pathology of cancers of the female genital tract

Pathology reports include not only histopathologic diagnoses but also specific information relating to prognosis and treatment; thus, pathologists must have sufficient familiarity with the staging classification and management of gynecological cancers to assure that their reports communicate clinically relevant information. On the other hand, full comprehension of the pathology report by the gynecological oncologist requires familiarity with the terminology used in gynecological pathology as well as the techniques of gross examination. This chapter summarizes the pathological features of the most common gynecological malignancies as well as an approach for processing gynecological biopsies and surgical specimens. Carcinoma of the vulva accounts for 4% of all female genital cancers and occurs mainly in women aged over 60 years. Squamous cell carcinoma is the most common type (86%). These tumors are divided into two groups: keratinizing squamous cell carcinomas unrelated to HPV (> 70% of cases), and warty and basaloid carcinomas, which are strongly associated with high-risk HPV (< 25% of cases), mainly HPV16 [1,2]. Etiologic factors and precursor lesions: Keratinizing squamous carcinomas frequently develop in older women (mean age, 76 years), sometimes in the context of long-standing lichen sclerosus. The precursor lesion is referred to as differentiated vulvar intraepithelial neoplasia (VIN) or VIN simplex (Fig. 1A), which carries a high risk of cancer development. In contrast, the less common HPV-associated warty and basaloid carcinomas develop from a precursor lesion called undifferentiated or classic VIN (1B). HPV-associated VIN lesions have a low risk of progression to invasive carcinomas (approximately 6%), except in older or immunosuppressed women [1,2]. Vulvar intraepithelial neoplasia (VIN). (A) Well-differentiated (simplex) type. The atypia is accentuated in the basal and parabasal layers. There is striking epithelial maturation in the superficial layers. (B) HPV-related undifferentiated (classic) VIN. Beneath a hyperkeratotic surface the epithelial cells are atypical. There are numerous mitoses. Pathology: VIN may be single or multiple, and macular, papular, or plaque-like. Histologic grades are labeled VIN I, II, and III, corresponding to mild, moderate, and severe dysplasia, respectively. However, grade III—which includes squamous cell carcinoma in situ [CIS]—is by far the most common. Keratinizing squamous cell carcinomas usually follow differentiated VIN (VIN simplex). Most tumors are exophytic but some may be ulcerative. Microscopically, the tumor is composed of invasive nests of malignant squamous epithelium with central keratin pearls (Fig. 2). The tumors grow slowly, extending to contiguous skin, vagina, and rectum. They metastasize initially to superficial inguinal lymph nodes, and then to deep inguinal, femoral, and pelvic lymph nodes [1,2]. Keratinizing squamous cell carcinoma of vulva. Nests of neoplastic squamous cells, some with keratin pearls, are evident. Clinica features: The FIGO staging of vulvar cancer defines tumors of any size limited to the vulva as Stage I carcinomas, tumors extending to perineal structures (lower third) as Stage II, tumors with positive inguinofemoral lymph nodes as Stage III, and tumors invading perineal structures (upper third) or distant metastasis as Stage IV. Tumor grade and number, size, and location of lymph node metastases determine survival. Better-differentiated tumors have a better mean survival, approaching 90% if nodes are negative. Two thirds of women with inguinal node metastases survive 5 years, but only one-fourth of those with pelvic node metastases live that long [3]. Prognosis correlates with stage of disease and lymph node status. The number of inguinal lymph nodes with metastases is the most important single factor. The prognosis of patients with vulvar cancer is generally good, with an overall five-year survival of 70% [1]. Vulvar verrucous carcinoma is a distinct variety of squamous cell carcinoma that manifests as a large fungating mass resembling a giant condyloma acuminatum. HPV, usually type 6 or 11, is commonly identified. The tumor invades with broad tongues. Verrucous carcinomas rarely metastasize. Wide local surgical excision is the treatment of choice. Basal cell carcinomas of the vulva are identical to their counterparts in the skin. They are not associated with HPV, rarely metastasize, and are usually cured by surgical excision. Although uncommon, malignant melanoma is the second most frequent cancer of the vulva (5%). It occurs in the sixth and seventh decades but occasionally is found in younger women. It is highly aggressive, and the prognosis is poor. Management should be according to guidelines for melanoma treatment elsewhere. The disorder usually occurs on the labia majora in older women. The lesion is large, red, moist, and sharply demarcated. The origin of the diagnostic cells (Paget cells) is controversial: they may arise in the epidermis or epidermally derived adnexal structures. Intraepidermal Paget disease may have been present for many years and is often far more the epidermis biopsies Paget disease of the which is associated with Paget disease is only rarely associated with carcinoma of the and metastases rarely treatment usually requires only local excision or [1,2]. of the vulva should be the deep and In local are for as VIN or Paget disease of the as well as invasive Stage I is in specimens. and the to and the structures intraepithelial lesions are often and to all surgical and should be [1]. This includes the vulva and to deep It is for that the vulva. The must be [1]. of vulva to the deep of the the of the and the of the It is usually with an inguinal lymph node which may be with the have been in of more limited but sufficient to the tumor with a The gross should include the size, of and all and of should be from the of the to the of tumor lymph nodes into superficial and deep and for [1]. malignant tumors of the are uncommon, of all genital Most malignancies to the are usually by and Squamous cell carcinomas for over 90% of Prognosis is to the of of the tumor the of The five-year survival for tumors to the is is only for those with [1]. occurs in years It in the of the and of some of which less in to be and may be cured by excision and tumors have often to lymph nodes, or distant in of patients survive with and [1,2]. in carcinoma by to cancer the second most common cancer in women. intraepithelial neoplasia is a of intraepithelial that with atypia and of intraepithelial to invasive squamous cell The dysplasia, and squamous intraepithelial lesion are commonly used (Fig. of in precursor This of the It the in more disease and terminology for the in situ intraepithelial neoplasia and The The also the corresponding from of the most superficial cells as well as the histopathologic lesions squamous intraepithelial and HPV to and cancer (Fig. is a HPV is and cell of must in the as a (Fig. In most of into the cell by and of HPV and and their tumor HPV into of the not and are in many of and all invasive in usually HPV and HPV and are found in 70% of invasive the other high-risk for 25% of HPV in the of Pathology: is a disease of squamous epithelium in the The by which squamous epithelium is in as by in and is with severe and The of from to is in [1,2]. features: The mean which women develop is years for and and years for on of of to and less invasive The for all grades of to to is years. of of to invasive carcinoma in that [1]. is with a the of the lesion and to be also to determine the of with are usually lesions are according to the of excision of a of the and may be [1]. less or 5 the squamous cell The tumor invades 5 deep and This tumor is stage according to The invasive or as epithelial from the of These (< of neoplastic epithelial cells not the prognosis of be with In the FIGO from Stage carcinoma to tumors Stage tumors are associated with lymph node metastases in of those that less or to have only a risk of lymph node or generally cancers less deep The of as a is more that of the of and of The in which of of the for examination. be for some that the of tumor in of by in which patients are to have lymph node other have that the of is an important [1]. Pathology: of cancer are often lesions or and exophytic the tumor is the be an which the and Most tumors are with nests of large malignant squamous cells and more cell Most cancers nests of cells in keratin cancer by and only rarely by the into in the corresponding are and to most common of of and may to to lymph nodes and tumor and are the for patients with is for stage and for stage years features: The the most for The stage of cancer is the of survival. five-year survival is and by stage I, II, III, and of patients develop on the or years of is for in younger or of the two are used for more tumors This tumor of The of with a mean of years Most tumors are of the cell type. These tumors are often associated with in situ and are frequently with HPV and [1,2]. in situ generally in the and into the squamous cell occurs in of of as a or of the by local and but overall survival is for squamous are usually The are long with to a of is to the of squamous neoplasia the or to determine carcinoma into the is the for women with and lesions (Fig. The is a but is often with or may also be as a for invasive carcinomas of the is a more of a as the is with or a The (A) and (B) should be and the (A) and to be a to and to and then in the with of and The is a excision of the to include a of with the and with of deep The should the with a a the of a should be and for is usually should be the in a (Fig. the and of the to be [1]. is for intraepithelial and many of is common for Stage I squamous carcinomas and for some Stage for the treatment of the the of the and in the that been for a from may be should be full to include the and all of the the and most and lymph nodes as and by location [1]. a of from or to Pathology: The only two of and intraepithelial neoplasia [1,2]. This is an of of size and with an in the with but factors include and atypia is the of have a to carcinoma to years. to carcinoma occurs in of women with atypia This lesion often as with and cell are large and with to of women be with carcinoma or the of to a neoplastic of cells with risk of the type of The diagnostic of is that that of many of the in and and [1,2]. features: is usually the of if a not more more or those with high may be with carcinoma is the sixth most frequent cancer in women with an of It is the most common cancer in women in and the most common of women with cancer are The is years [1,2]. carcinoma is into two (Fig. and I tumors (Fig. carcinomas, are often by or and are associated with They mainly in or women and are associated with and most carcinomas are to the and follow a In contrast, type tumors (Fig. are carcinomas, occasionally in or from lesions in tumors are not associated with or and and are highly [1]. of the (A) tumor with only superficial Well-differentiated The neoplastic (B) and tumor with deep carcinoma of tumor cells and cancer is the most common cancer in women with cancer a in that is also associated with cancers of been to cells into carcinoma and of in and tumor carcinomas, of and of on malignant have been in type I of the and with In contrast, most type carcinomas have and of on carcinomas may also from carcinoma with tumor progression and The the most of carcinomas to the classification of carcinoma I and to distinct an a a and a if of the to in On the other hand, patients with tumors that are the from that are used for carcinomas Pathology: of the This type of cancer is composed of cells and is the most common The FIGO tumor into grades on the of the of to the common with squamous and the and associated with prognosis and of the (Fig. It often to intraepithelial been intraepithelial not to be with with type of tumor to be and as if they of the (A) of tumor from the (B) The tumor atypia and cell is a tumor of older women. It large cells with or cells with that cell carcinomas have a In highly malignant epithelial cells with These are derived from a common to be of epithelial five-year survival is 25% [1,2]. features: cancer may to lymph nodes, pelvic with cancers may also develop metastases of with with cancers to the are usually by is the tumor is differentiated or in is the is or lymph nodes in carcinoma is to for and other risk as of and of survival of all patients with cancer treatment is years, to years. that have the or are more to have the cancers the have a the the are into and undifferentiated less of They may be or may the The tumor cells cells in the atypia may be to severe and may be of and and the The most common of is a and which in a and as [1,2]. The features and undifferentiated It may as an or a Microscopically, of cells that are sometimes associated with a cell usually is striking and more is usually the as a of [1,2]. differentiated in the are as undifferentiated [1,2]. features: years may and metastases may if the tumor to the usually the by survival and are contrast, generally with with patients with those with and undifferentiated have and more frequent and are more to of be with and with an of 90% survival years [1,2]. is a tumor with epithelium and malignant It should be from in which epithelial and are and which is highly of patients with with and to local or [1,2]. is a of origin is only that of It accounts for of is with are on more a older those with and the malignant tumors are [1,2]. Pathology: should be if an is of on gross or of or more and are the diagnostic (Fig. and and may only is important as tumors less 5 in Most are large and are They are usually of and survival is 25% [1,2]. all are high grade tumors their is a of tumors features that are for the of or have an These tumors have been as tumors of malignant but the as by the classification of tumors in of their in most The the the and which for the In two of and of only and patients years in the of in and as in the other patients and disease is of tumor cell size of and of the tumors be to or malignant with and the be in most from an or should be in single and is often sufficient for diagnostic all with a of for determine the of and or The gross must include the size, or and of (Fig. the the of the (Fig. should of the of tumor of to which tumor (A) of from to tumor is (B) of tumor exophytic and of of tumor is generally as and invasive into a with from and [1]. for the includes and deep to a tumor and to determine an cancer the the for and with or of tumor with from and [1]. may be in the staging of of with of all lymph nodes is [1]. node is the size is of the are Most malignancies are with women aged years. that some of carcinoma of the may arise from the of the carcinomas to carcinoma and frequently as a mass in the of a but may sometimes only be examination. The tumor is in 25% of Prognosis is as the disease is stage [1,2]. common for is for patients have a of or a of the is with the corresponding should be for (Fig. [1,2]. and the for in a of the of the and the and in the with of and The for and the for processing The is initially for to of the epithelial the is from the and into and the is for There are many of tumors and malignant in women of of tumors are 90% of malignant and tumors are the of years tumors are by the cell type of Most are common epithelial tumors (approximately important are cell tumors tumors and tumors to the epithelial tumors for 90% of the most common cancer is the second most frequent cancer and carries a all other female genital cancers is to in is over of patients have tumor to the or the of of common epithelial origin be according to cell of and or of of and epithelial most commonly women and frequently in women in been by or the risk for cancer in the is women with with cancer have a women with a of carcinoma are risk for cancer and in in and are in cancers as for women with cancer are also risk for cancer tumors are according to cell type into and squamous cell tumors However, of cells are found in the and their long been to of the surface epithelium the is by which also the The to from which the and arise (Fig. the tumor cells the of the or been that cells to distinct neoplastic which the of the is that a number of have been to be cancers in other pelvic and the In been that some carcinomas arise from precursor epithelial lesions in the of the and cell carcinomas from of epithelial tumors epithelial that in their counterparts and in to carcinomas, is of and their prognosis is better that of tumors generally in women aged years tumors are more commonly or other The tumors in size, tumors may be tumors have or more to by from and to These structures epithelial and the of more nests of epithelial cells into the a tumor as carcinoma a tumor [1,2]. the of those with exophytic on (Fig. rarely of to and the (Fig. invasive and are identical lesions only by the of the disease and the of the invasive are superficial lesions of or size frequently as disease of (A) The of nests of tumor cells are present a (B) The tumor and a and a occurs if the tumor is to the if to the or 90% of patients are 5 years. Although is a of the tumors rarely years. progression to carcinoma been in of tumors may as carcinomas in the tumors should be tumors of the are most common in women aged years and are the of years. on and carcinomas are into in of carcinomas (> carcinomas cell carcinomas carcinomas and carcinomas (< 2). These which for of carcinomas, be and are as by in and risk precursor of to and management of is and carcinomas are tumors are frequently associated with tumors and have of or carcinomas precursor lesions and have a high of in but not in or carcinomas in patients with or are the type and commonly have Pathology: carcinomas called are the most common cancers and most patients present with stage disease (approximately of cancers with are They are usually with and and Most tumors have a high grade with highly and (Fig. The is are often present of the of which for of (A) (B) and cell carcinomas by nests of tumor cells The of the is the for and carcinomas (Fig. carcinomas rarely to tumors tumors are often and invasive carcinoma may the a that tumor progression occurs from and tumor to and invasive This is by in of and of carcinomas with tumors Pathology: carcinomas are usually large, They often (Fig. and malignant may a single tumors should be tumors are in only of the thus, or tumors should of metastases from a carcinoma The of tumor with intraepithelial carcinoma is for tumors that features of invasive carcinoma malignant cells tumors with intraepithelial carcinoma have a low of or to have a more prognosis carcinomas with The of high and tumor should be a of for Stage I is a of or in the and frequently tumors the The is also by a tumor in of the and in the that in most the tumors are metastases from the lesions [1,2]. (Fig. may have of squamous and is second only to in It accounts for of all These tumors most commonly to of cancers are most tumors are to the or the [1,2]. carcinomas are to arise by malignant of and not from surface The most common in carcinoma of the are of the and and tumors also have Pathology: Although they may be most carcinomas are with of These tumors are their and of patients also a that most of arise some may be metastases from or the This important [1,2]. This cancer is to and often occurs in with It of all cancers usually The most common are of the and Although patients present with Stage I or cell carcinomas have a prognosis with other cell carcinomas of the their counterparts in the vagina, and they or of malignant cells with (Fig. features: the cancers are many have to the of the or tumors have a to in the on the and is to lymph nodes the origin of the and to a to or inguinal lymph nodes [1,2]. for patients with malignant tumors is generally poor. The most important is the surgical stage of the tumor five-year survival is only for epithelial tumors also include type and the size of the which the the and the of is the of The and all must be and as tumor as is used to distant of tumor derived from cells one-fourth of In cell tumors are all but in and they are In cell tumors are the most common cancer they are cell tumors may arise from of the female genital In the tumors most from a cell of [1,2]. are composed of neoplastic cells, to of or tumors and less and cells to those the cell tumors in women older years usually from of of the of a cell tumors to be highly with survival for many [1,2]. cell highly diagnostic factors and and that are in according to their stage [1,2]. is the of and is composed of It accounts for less of cancers in all women. Most patients are and years. The tumors are in of Pathology: are often large and and have a The surface is and They large nests of tumor cells that have and central the tumor [1,2]. are survival for patients with Stage I tumor the tumor is highly to for tumors five-year survival is a tumor of cell origin that structures. Most from two and usually all layers. derived from the layers. However, These tumors for of malignant tumors in women the of Microscopically, they as and and other structures found in is on the of correlates with tumor grade [1,2]. tumors are highly malignant of women the of that the and of the and and They are large, with and The most common is the are They of that into by tumor cells, resembling the The are by a of cells and a and a central tumors which should be for in all cell of in the is for and for the of five-year survival with for Stage I tumors [1,2]. of the is a tumor that the epithelial of and The is positive and the of may to and in or in older In women of age, may also be a metastasis from an The tumor is and Although highly aggressive, well to [1,2]. These tumors of from to and may female and cells) or and cells) structures [1,2]. cell tumors are the of the associated with They should be malignancies of their for local and the of distant Most cell tumors and are occurs in and women and distinct and features and Pathology: cell tumors are large and to The surface to cells, of and a central a Tumor cells a that of and are the most important positive [1,2]. features: of cell tumors is a common may develop if a cell tumor 90% of cell tumors are the 90% of patients survive years. that have into the and have a surgical is not years and is usually [1,2]. cell tumors are of low malignant that Tumor cells cell tumors all but are most common in women of They from well to differentiated and some have and of all patients with cell tumors of are often as and of the tumor is or Well-differentiated tumors are cured by surgical but differentiated may metastasize [1,2]. cell tumors of the also called cell are composed of cells that cells, cells, and Most cell tumors are usually with of cancers found in the arise in the large and in These tumors from lesions to large tumors large to most often in the and may be tumors are metastases to the composed of nests of cells in a derived from the The is the in of and most of the are from the [1,2]. and a and are in of the tumor is or and the tumors are and all should be the and and include tumor with of tumor for the which may be in or over the tumor It may cell tumors should be [1]. the mass to metastasis from or elsewhere. and of or for all that are malignant by or for or the with of lesions or for of Stage I or disease by and of pelvic and the for the the of of disease location and with or to the the in the of a carcinoma or the surface for tumor and any to metastases the FIGO stage from Stage I to Stage for tumor and is any to two should be In over of the of lymph all These are often and should be The by from the and and of These should be by and cell is The disease is a of with and as well as derived from is a with resembling of and of are often 5 in and usually from of an that Most a of by to but and also as in which only the is are not in of the a develop and are with a have a risk of a the [1,2]. Pathology: Microscopically, many have is and composed of and atypia is features: are and of include and The most important is of which occurs in of of of the and of to of patients for but a is The of a may only the superficial or they may the and the broad They to of the and to distant the is a but occurs in only a of [1,2]. occurs in of of of and of most other tumor the tumors are and and tumor is to the of the There is a of and with of is to the tumors any if are and not [1,2]. invades mainly in the It the to and of risk factors and and most patients are tumors are the common and are mainly composed of and may be present as of cells are tumor is from by the of in Most cells but a [1,2]. tumor must be to local It sometimes and may be tumors and of more 5 are associated with The of to The is not for the or of any information by the should be to the corresponding for the