Nodular histiocytic hyperplasia is a rare lesion often incidentally encountered in endometrial biopsies. Majority of these lesions are reported in the literature as single case report. The largest series, so far has been reported in the literature, is based on 7 cases . The lesion, when encountered in endometrial biopsies and present in small fragments, may mimic a neoplasm. So far all the reported cases are, however, associated with benign diseases. The current report is based on a case of nodular histiocytic hyperplasia associated with a FIGO I/III endometrial endometrioid adenocarcinoma. The lesion itself is identified grossly in its entirety as a distinct entity presenting as an endometrial polyp.
The differential diagnoses of this entity include Langerhans cell histiocytosis, xanthogranulomatous endometritis, malakoplakia, signet-ring cell changes of the endometrial stromal cells, etc. Available reports in the literature have elaborated how to distinguish nodular histiocytic hyperplasia from their mimics. The current case showed some resemblance with perivascular epithelioid cell tumor (PEComa) or an epithelioid smooth muscle tumor with many small hyalinized blood vessels. Microscopic and multifocal PEComa of the female genital tract have been reported [6, 7]. One interesting finding noted in the current case is the presence of hyalinized fibrous strands throughout the lesion; a feature often seen in endometrial stromal tumors. The cytologic appearance of the tumor cells seen in endometrial stromal tumor is, however, completely different from what was seen in nodular histiocytic hyperplasia. The cells in endometrial stromal tumor are small, mostly round and darkly stained, especially in low grade stromal sarcoma.
Special stains that were performed to rule out the mimics show the lesional cells of nodular histiocytic hyperplasia are strongly and diffusely reactive to histiocytic marker, CD68. All other markers including, epithelial markers (AE1/AE3), smooth muscle markers, and endometrial stromal cell marker (CD10) were non-reactive. HMB45, a marker for PEComa, was also negative.
The site of nodular histiocytic hyperplasia was clearly located on the surface of endometrium with smooth lining and protruding into the endometrial cavity.
It is speculated that the nodular histiocytic aggregates may result from previous endometrial biopsy. The current case did have a recent history of endometrial biopsy one month prior to her hysterectomy. The previous biopsy in this case revealed endometrial carcinoma with squamous differentiation and no evidence of histiocytic aggregate. It is also of note that the appearance of the foamy histiocytes often seen in endometrial biopsies is also different from the histiocytes present in nodular hyperplasia as they lack the foamy cytoplasm.
Mazur and Kurman  proposed that these histiocytes apparently reside in the endometrial cavity and reported their presence in association with hydrometra and benign bleeding patterns. The authors postulated that it may represent a response to what they have proposed as “intracavitary debris.” The current case was associated with an endometrioid adenocarcinoma so presence of some “intracavitary debris” is not unlikely. As noted before the polypoid lesion was seen projecting into the endometrial cavity.
A possibly related, but morphologically dissimilar, histiocytic endometrial lesion has been reported by Iezzoni and Mills in their study of non-neoplastic endometrial signet-ring cells . No signet-ring cells are identified in this case.
Kim et al. proposed that the endometrial stromal cells showing progestational changes with atrophic endometrial glands trapped in the middle may produce histologic similarities that may vaguely resemble histiocytic aggregate . Unlike nodular histiocytic aggregate, decidualized stromal cells do not form a discrete nodule. Kim et al. also speculated that the nodules may not originate in the endometrium because no vasculature was seen in their cases . The current case documents many blood vessels in the nodule and thus contradicts that speculation of Kim et al.
In conclusion, nodular histiocytic hyperplasia may not always be associated with benign/inflammatory lesions as previously reported in the literature. The current case documents its association with endometrioid carcinoma of the endometrium.
The patient is currently followed routinely and is disease free 80 months after surgery.
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