SQUAMOUS CELL CARCINOMA

Clinical features

• These tumors, when pure, account for at most 0.5% of wndometrial carcinomas; only about 70 cases have been documented. Two-thirds of the patients are postmenopausal (mean age,67 years). The tumors are stage III or IV in one-third of cases. The survical is 70-80% with stage I tumors but only 20-25% with stage III tumors.
• Predisposing factors present in some cases have included chronic pyometra, cervical stenosis, uterina prolapse or inversion, extensive endometrial squamous metaplasia, and a history of pelvic radiation. Human papillomavirus (HPV) has been detected in rare neoplasms.
• Dalrymple and Russell have questioned the validity of Fluhmann's third criterion as it artificially categorizes tumors involving both the endometriium and cervix as cervical in origin, and fails to recognize the possibility of a multifocal squamous cell carcinoma arising in the cervix and the endometrium.

Pathologial features

• The tumors often have a nonspecific gross appearance, but can occasionally have a white, sometimes even condylomatous appearance.
• Many tumors are obviously malignant on histological examination, but others are very well differentiated. In a curettage specimen, the latter can appear as fragments of almost normal-appearing, glycogenated squamous wpithelium devoid of cellular atypia. Hysterectomy in such cases may show myoinvasive, still highly differentiated, squamous cell carcinoma.
• Rare tumors have been interpreted as verrucous carcinomas are the endometrium. Bona fide verrucous carcinomas are much less common than well-differeniated squamous cell carcinomas, which have a surface verrucoid component but an infiltrative, rather than the pushing, deep border of a verrucous carcinoma.
• Some squamous cell carcinomas that have a prominent spindle cell growth of neoplastic epithelial cells are appropriately designated sarcomatoid squamous cell carcinoma.
• Horn et al, found that although four of their eight cases were immunoreactive for p16,only one cantained HPV.

Strumal Carcinoid

Clinical features and behavior

• These tumors have a similar frequency to insular carcinoids, and occur throughout adult life, The clinical presentation is usually related to the presence of an adnexal mass. One case had peritoneal implants of struma at the time of oophorectomy.
• The carcinoid syndrome has been found in only rare cases, but manifestations suggesting function of the thyroid component have been present in 10 %. Chronic constipation relieved by removal of the tumor has been a symptom in rare cases.
• The tumors are almost always clinically bening. There has been only one reported fatality. 2.5 years postoperatively.

Pathological features

• The sectioned surface is usually homogeneous, yellow or tan, and solid, but may ve variably cystic. The strumal and carcinoid components are each growly recognizable in occasional cases.
• On microscopic examination the tumors consist of two components, which are usually admixed but occasionally only contigunous, one being a trabecular or mixed trabecular-insular carcinoid, and the other typical truma ovarii.
• Glands or cysts lined by mucinous epithelium are seen in half the cases and bay be conspicuous; rarely there may be an admixed mucinous carcinoid.
• The tumors are usually immunoreactive for chromogranin, synaptophsin,serotonin prostatic acid phosphatase and in 40%, neurohormonal peptides, including peptide YY in patiens with constipation. The strumal component is typically  positive for thyroglobulin and TFF-1.

Cellular Leiomyomas and Highly Cellular Leiomyomas

• These tumors grossly may resemble typical leiomyomas but often have a fleshier, soft, yellow or brown sectioned surface, sometimes with hemorrhage and/or necrosis. They may be less well circumscribed than typical leiomyomas.
• Cellular leimyomas are defined as leiomyomas that are 'significantly' more cellular than the normal myometrium but which are otherwise typical.
• Highly cellular leimyomas (HCL) are characterized by a cellularity similar to that of an endometrial stromal tumor (EST), and may be misdiahnosed as an endometrial stromal nodule when well circumscribed.
• Features that facilitate the distinction of HCLs from an EST and include a fascicular growth pattern, spindle-shaped tumor cells, blood vessels with thick muscular walls, cleft-like spaces, and immunoreactivity for desmin and h-caldesmon. About 40% of HCLs are CD10 positive, but CD10- negativity favors HCL over an EST.
• Recently described markers that are expressed in smooth muscle tumors but not stromal tumors that may also aid this differantial are indicated elsewhere.
• The differantial of CLs also includes focal hypercellularity of the myometrium. This finding is more common in postmenopausal women and tends to involve superficial myometrium immediately subjacent to the endometrium. The absence of a mass, the sometimes band-like arrangement, and merging with normal myometrium facilitate the diagnosis.

MUCİNOUS CARCİNOİD

CLİNİCAL FEATURES AND BEHAVİOR

• This tumor is the least common variant of ovarian carcinoid. Bases on the only series of such cases (Baker et al.), the age range has varied frıom 14 to 74 years and the clinical presentation is nonspecific.
• Most ofthe reported tumors have been clinically benign, except for several tumors with a carcinomatous component (see below) that had extraovarian spread at presentation and a fatal course.

PATHOLOGİCAL FEATURES

• The tumors, which range up to 30 cm in diameter, may be entirely solid but more commonly form a mural mass in a mature cystic teratoma or other type of cystic ovarian tumor (mucinous borderline tumor or carcinoma, borderline Brenner tumor, epidermoid cyst). Two tumors were intimately admixed with yolk sac tumor.
• Mucinous carcinoids can be divided into there categories based on their microscopic appearance: 

1. 'Well-differentiated' tumors are composed of small glands, sometimes lying within pools of mucin, lined by goblet cells and differentiation. The cells show minimal atypia.
2. 'Atypical' tumors contain crowded to confluent glands, small islands with a cribriform pattern, and scattered microcystic glands, with cells similar to those in the well-differentiated tumors and mild to moderate atypia.
3. 'Carcinoma arising in mucinous carcinoid' are camposed of solid nests or closely packed glands composed of mucin-poor cells that are markedly atypical and mitotic. Signet-ring cells are also usually prominent. Foct of well-differentiated or atypical carcinoid are typically present.

• The tumor cells are variably immunoreactive for synaptophysin and chromogranin. One or more intestinal-type polypeptide hormones have also been found in some tumors.
• Other elements present in some tumors have been noted above. Additionally, occasional tumors have contained a component of insular, trabecular, or strumal carcinoid.

Histiocytic Nodules

• Nodular aggregates of histiocytes resembling Langerhans'/interdigitating cells can occur in the  endometrium. The examples described by Kim et al. were an incidental microscopic finding in curettage specimens in women of reproductive age. The nodules were solitary and 0.3-1.5 cm in maximum.
• The histocytes are round to polygonal with distinct cytoplasmic borders and moderate amounts of pale amphophilic or eosinophilic granular cytoplasm. Small cytoplasmic vacuoles, but not cytoplasmic lipid or pigment, may be present. The avoid to reniform nuclei have occasional grooves, fine chromatin, and inconspicuous nucleoli. Mitoses were frequent in one case.
• The cells are immunoreactive for CD68 and lysozym but negative for S100 and cytokeratin.
• Uterine involment by Langerhans' cell histocytosis can be excluded by the absence of eosinophils as well as negative staining for S100. The distinctive apperance of the histiocytes, their nodular arrangement, and the absence of lipid and/or pigment xanthogranulomatous endometritis.

MONODERMAL TERATOMAS

Struma Ovarii

• The term 'struma' is reserved for cases in which thyroid tissue is the predominant or sole component or forms a grossly recorgnizable tumor in a teratoma.
• The peak frequency is in the fifth decade, but occasional cases occur much earlier or later. When clinically significant (many are incidental findingsin a resected dermoid), the presentation is similar to that of any ovarian mass. In rare cases, however, there is clinical evidence of hyperthroidism.
• Ascites is present in as many as a third of cases, and occasionally is accompanied by Meigs' syndrome. The association of a pelvic mass, ascites, and an elevated serum level of CA-125 can mimic ovarian cancer.

PAPILLARY PROLIFERATION

• Lehman and Hart have describe localized papillary endometrial proliferations that could lead to a misdiagnosis of a villoglandular endometrioid adenocarcinoma,especially in a fragmented biopsy or curettage specimen.
• The lesions typically occur in postmenopausal women who present with bleeding. Two-thirds of the lesions involved polyps, but in some cases the lesion occured in the absence of, or at a distance from, a polyp.
• The proliferations are characterized by papillae with fibrovascular cores and variable degrees of branching. The papillae are covered by epithelial cells with bland to mildly atypical nuclei, with occasional mitotic figures in some cases.
• One or more metaplastic epithelial changes are often present, including (in descending order of frequency in the cited study) mucinous, eosinophilic cell, ciliated cell, squamous, and hobnail cell metaplasia.
• The patients had uneventful outcomes, but only three who were not treated by hysterectomy had appreciable follow-up.
• Awareness that the lesion tend to occur in polyps, the typically bland cytologic features, and the usual presence of metaplastic epithelia facilitate the diagnosis.