Xanthogranulomatous Change in a Leiomyoma: First Report of an Extremely Rare Variant/Degenerative Change.

A 47-year-old female presented with abnormal uterine bleeding and lower abdominal pain for the past 5–6 months. Her cycles ranged from 18 to 26 days, with heavy menstrual flow associated with dysmenorrhea. She had four children and her last childbirth was 15 years back. There was no history of discharge per vaginum. Her medical, surgical, and family history was not statistically significant. On examination, the uterus was 18-week in size, uniformly enlarged mobile soft and nontender with normal adnexa. Her hemoglobin was 10.2 g% with microcytic hypochromic red cell picture. The rest of hematological and biochemical investigations were within the normal limits. On sonography, an echogenic mass measuring 6.5 cm × 5 cm × 4.5 cm was observed in the posterior wall of the uterus, suggestive of fibroid. Hysterectomy was performed. On gross examination, a specimen of uterus and cervix was received measuring 12.5 cm × 11 cm × 8 cm. On serial sectioning, a large circumscribed intramural mass measuring 6 cm × 5 cm × 4.5 cm was observed bulging into the endometrial cavity and distorting it. Cut surface was gray–white to gray–yellow and showed whorling [ Figure 1 ]. Specimen of uterus and cervix showing a large circumscribed intramural mass bulging into the endometrial cavity, cut surface of which is gray–white to gray–yellow and showed whorling Microscopically, the tumor was composed of interlacing fascicles of smooth muscle cells. There were multiple foci of necrosis, and infiltration by foamy macrophages (some of which were hemosiderin laden) admixed with lymphocytes, plasma cells, cholesterol clefts, and multinucleated giant cells [ Figure 2 ]. Extensive sampling of the tumor was done, but there was no evidence of nuclear enlargement, pleomorphism, hyperchromasia, or brisk mitosis, thereby ruling out malignancy. On immunohistochemistry, histiocytes were strongly positive for CD-68 [ Figure 2 ]. Hence, a final diagnosis of xanthogranulomatous variant/degenerative change in a leiomyoma was rendered. Photomicrograph showing (a) sheets of foamy macrophages along with cholesterol clefts (H and E, ×100), (b) Foam cells admixed with lymphocytes, plasma cells with smooth muscle bundles seen at the periphery (H and E, ×200), inset immunohistochemistry for CD68 was strongly positive in histiocytes

Xanthogranulomatous inflammation (XGI) is a rare distinct type of chronic inflammation histopathologically characterized by infiltration by sheets of foam cells and hemosiderin-laden macrophages admixed with chronic inflammatory cells such as lymphocytes, plasma cells, occasional neutrophils with or without multinucleated foreign-body giant cells or Touton giant cells. XGI is also referred to as pseudoxanthoma and histolytic endometritis by several authors in the literature.[ 1 - 3 ] XGI has been reported most commonly in the kidney, gallbladder, salivary glands, and bones while the female genital tract being an unusual location.[ 1 - 3 ] Myometrial xanthomatosis, a term designated for nodular or diffuse histiocytic hyperplasia of the myometrium, has been reported by several authors in association with pregnancy-related procedures.[ 4 ] Moreover, Adany et al .[ 5 ] reported that histiocytic counts were significantly higher in leiomyomatous areas than in adjacent normal myometrium. Xanthogranulomatous inflammation of the endometrium in a leiomyoma has been reported by only a few authors.[ 4 - 8 ] The first evidence of collections of lipid-laden macrophages was reported by Lim et al. as yellowish degeneration of uterine leiomyomas.[ 8 ] We report a case of xanthogranulomatous change in a leiomyoma in a 47-year-old female who presented with abnormal uterine bleeding. To the best of our knowledge, this is the first report of xanthogranulomatous variant/degenerative change in a leiomyoma.

The index case highlights a new variant of leiomyoma which both gynecologists and pathologists should be aware of as it may either mimic carcinoma or coexist with it. The necrotic, irregular mass on gross may present a diagnostic challenge for gynecologists, while microscopically, the foamy histiocytes infiltrating the myometrium may create a dilemma for the pathologists as it may be misinterpreted as a clear cell carcinoma or sarcoma. Immunohistochemistry may easily distinguish the XGI from malignancy. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Nil. There are no conflicts of interest.

XGI, a specific form of chronic inflammation, marked by parenchymal destruction, proliferative fibrosis, and infiltration of typical foamy histiocytes admixed with hemosiderin-laden macrophages and foreign-body giant cells. XGI is most frequently observed in pyelonephritis and cholecystitis, although more recently, it has been reported in almost all organs such as bronchi, lung, endometrium, vagina, fallopian tubes, ovary, testis, stomach, colon, ileum, lymph nodes, and bladder. In the female genital tract, xanthogranulomatous salpingo-oophoritis is much more common than XG endometritis or cervicitis. A variety of theories have been proposed for XGI of the female genital tract, namely suppurative infections (by Escherichia coli , Proteus spp., Staphylococcus aureus , Bacteriodes fragilis , and Salmonella typhi ), organ obstruction, endometriosis, intrauterine contraceptive device, inborn errors of lipid metabolism, etc.[ 1 - 3 ] Xanthogranulomatous endometritis patients usually present with abnormal uterine bleeding, purulent discharge, pyometra, or hematometra. XGI causes the destruction of the involved organ and could be misinterpreted as a locally invasive cancerous lesion. Moreover, XGI may have association with chronic diseases such as diabetes mellitus and tuberculosis.[ 3 ] An elevated white blood cell count and raised erythrocyte sedimentation rate are usually found in laboratory tests. Preoperative diagnosis of XGI is very challenging on account of nonspecific presenting symptoms and radiological imaging. Histopathology remains the gold standard for establishing a diagnosis of XGI, characterized by tissue destruction and infiltration by sheets of foam cells intermixed with chronic inflammatory cells such as lymphocytes, plasma cells, and occasional neutrophils with or without multinucleated foreign-body giant cells. In addition, foci of necrosis, cholesterol clefts, or dystrophic calcification may also be present. Immunohistochemistry serves as an adjunct in the diagnosis of XGI, histiocytes being positive for vimentin and CD68 as in the present case.[ 1 - 3 ] A diffuse or nodular histiocytic hyperplasia designated as myometrial xanthomatosis has been observed in associated with pregnancy-related procedures, an exaggerated reaction to a surgical procedure/suture material, chronic inflammatory processes, thereby representing a response to a variety of myometrial insults.[ 4 ] The differential diagnosis of histiocytic hyperplasia of the myometrium includes a wide range of infectious, inflammatory, and neoplastic disorders. Xanthogranulomatous endometritis typically occurs in postmenopausal women with a well-documented association with endometrial hyperplasia and carcinoma. Malakoplakia is another unusual variant of histiocytic endometritis with the hallmark Michaelis–Gutmann bodies, i.e., intra- and extracellular calcified spherules. In developing countries like India, tuberculosis as well as fungal infections are an important cause of histiocytic infiltrates. Rarely, Langerhans cell histiocytosis can occur in the female genital tract, the neoplastic Langerhans cells display typical longitudinal nuclear grooves and are admixed with eosinophils; moreover, Langerhans cells are positive for CD1a and S100 protein.[ 4 , 6 , 7 ] A significantly higher histiocytic count in leiomyomatous areas compared to adjacent normal myometrium was first observed by Adany et al .[ 5 ] Histiocytes were diffusely scattered throughout the leiomyomas while in the normal myometrium, they could be detected only in the connective tissue septa separating the bundles of smooth muscles. Histiocytes were assessed by immunoreactions for factor XIIIA, leading to speculation on its role in the pathogenesis of leiomyoma.[ 5 ] Yellowish degeneration in a series of five cases of uterine leiomyomas was first observed by Lim et al .[ 8 ] They concluded that this reflected the accumulation of lipid within degenerating hypercellular leiomyoma or a secondary degenerative change with xanthoma cell collections. To the best of our knowledge, the present case is the first report of xanthogranulomatous variant/degenerative change in a leiomyoma. The treatment options for xanthogranulomatous variant of leiomyoma include myomectomy or hysterectomy depending on the need for preservation of fertility. Associated pyometra should be drained and culture and sensitivity of the pus should be performed. Extensive sampling of tissue is required to rule out any coexistent foci of neoplastic growth.