There are several special variants of adenocarcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is an extremely well-differentiated form of adenocarcinoma in which the branching glandular pattern strongly simulates that of the normal endocervical glands. The lining cells have abundant mucinous cytoplasm and uniform nuclei (44,45). Because of this, the tumor may not be recognized as malignant in small biopsy specimens, thereby causing considerable delay in diagnosis. Special immunohistochemical staining may be required to establish the diagnosis. Earlier studies reported a dismal outcome for women with this tumor, but more recent studies found a favorable prognosis if the disease is detected early (46). Although rare, similar tumors were reported in association with endometrioid, clear, and mesonephric cell types (47).
An entity described as villoglandular papillary adenocarcinoma deserves special attention (48). It primarily affects young women, some of whom are pregnant or users of oral contraceptives. Histologically, the tumors have smooth, well-defined borders, are well differentiated, and are either in situ or superficially invasive. Follow-up information is encouraging. None of these tumors recurred after cervical conization or hysterectomy, and no metastasis was detected among women undergoing pelvic lymphadenectomy. This tumor appears to have limited risk for spread beyond the uterus.
Carcinomas with a mixture of malignant glandular and squamous components are known as adenosquamous carcinomas. Patients with adenosquamous carcinoma of the cervix were reported to have a poorer prognosis than those with pure adenocarcinoma or squamous carcinoma (49). Whether this is true when corrected for size of lesion is controversial (38,39).
In mature adenosquamous carcinomas, the glandular and squamous carcinomas are readily identified on routine histologic evaluation and do not cause diagnostic problems. In poorly differentiated or immature adenosquamous carcinomas, however, glandular differentiation can be appreciated only with special stains, such as mucicarmine and PAS. In one study, 30% of squamous cell carcinomas demonstrated mucin secretion when stained with mucicarmine (47). These squamous cell carcinomas with mucin secretion have a higher incidence of pelvic lymph node metastases than do squamous cell carcinomas without mucin secretion, and they are similar to the signet-ring variant of adenosquamous carcinoma (47,50).
Figure 36.5 Invasive adenocarcinoma of the cervix, well-differentiated. A. Irregular glands are lined with tall columnar cells with vacuolated mucinous cytoplasm resembling endocervical cells. B. Nuclear stratification, mild nuclear atypism, and mitotic figures are evident in higher power.
Glassy cell carcinoma is recognized as a poorly differentiated form of adenosquamous carcinoma (51). Individual cells have abundant eosinophilic, granular, ground-glass cytoplasm, large round to oval nuclei, and prominent nucleoli. The stroma is infiltrated by numerous lymphocytes, plasma cells, and eosinophils. Approximately half of these tumors contain glandular structures or stain positive for mucin. The poor diagnosis of this tumor is linked to understaging and resistance to radiotherapy.