Florid histiocytic reaction to oxidized cellulose masquerading as ovarian malignancy: Report of two cases

Prompt control of bleeding is a crucial requirement in most surgical procedures. When conventional methods like ligature and thermo-coagulation are ineffective, supportive topical hemostatic agents are frequently used to hasten the events.[] Compared with electrocautery or ligation, the latter has the added advantage of controlling bleeding without vascular occlusion or thermal injuries.[] These hemostatic agents are bioabsorbable materials which are often left in the surgical field to prevent further bleeding.[,] The commonly used hemostatic agents include hemostatic sponges (Gelfoam/Surgifoam), oxidized cellulose-based (Surgicel, Curacel), collagen-based (e.g., Instat), fibrin sealant using wound fibrinogen, bicomponent fibrin sealant, and so on. Among these, oxidized regenerated cellulose (ORC) is widely used.[,,,] Although generally considered to be biodegradable, in some cases ORC causes adverse events with mass effect and recurrence of symptoms. The condition often mimics malignancy on radiologic imaging and histopathology.[,,] This article highlights two cases of ORC-induced ovarian pseudotumor. CASE REPORTS Case 1 A 46-year-old female came with complaints of right-sided pelvic pain. Ultrasound examination revealed bilateral complex ovarian cysts, and the larger cyst measured 5.7 cm in diameter. The ovarian cysts were excised; part of the tissues appeared soft pearly white and gelatinous. Her history was relevant for bilateral ovarian endometriosis diagnosed and operated upon a year back. Case 2 A 33-year-old lady presented with lower abdominal pain of few weeks duration. She was suspected to have a ruptured right ovarian cyst, but at surgery was noted to have tubo-ovarian adhesions which were excised. Five months prior she was operated for a cystically enlarged right ovary measuring 11 × 5.5 × 4 cm with extensive adhesions to pouch of Douglas, adnexae, and uterus. Her history was relevant for a large right ovarian follicular cyst excised 2 years ago. The last two surgical biopsies displayed similar morphology. Histopathologic examination of the tissues from both cases showed sheets of large cells interrupted at places by short delicate fibrous septa. The cells were featured by abundant pale bluish, occasionally bubbly cytoplasm, and small central or peripherally displaced nuclei with some cells having “signet ring” appearance [Figure 1a and b]. At places, small pools of basophilic mucin-like material were noted. No gland formation, mitotic activity, or lymphoplasmacytic or neutrophilic infiltrates were noted. The cells were strongly highlighted by Gomori silver methenamine and diastase-PAS stains and weakly mucicarmine positive [Figure 2a and b]. Immunohistochemical (IHC) staining revealed negativity for pan-cytokeratin and strong positivity for CD68, confirming the histiocytic nature of the cells [Figure 2c and d]. No evidence of endometriosis was identified. In addition, the second biopsy of case 2 also showed amphophilic foreign body material, some of which were rimmed by multinucleated histiocytic giant cells [Figure 2e and f]. On further enquiry, it was confirmed that in both the patients, at the time of the initial surgeries, hemostasis was ensured by generous packing with ORC. The inflammatory response was noted only in the surgical sites where ORC was used. Thus, the final diagnosis was florid histiocytic reaction in response to ORC.

The use of bioabsorbable ORC to control intraoperative bleeding has become a common practice in gynecologic and other types of surgeries.[,,] ORC is generally accepted as a safe topical hemostatic agent.[,] The ease of use, favorable biocompability, and bactericidal properties are other reasons for its wide popularity.[] ORC, first introduced by Frantz in 1942, is produced by regenerating cellulose after decomposition of wood pulp.[,] It is available as loosely fibrillar, malleable, and trimmable material.[] ORC is thought to act by causing lysis of red blood cells with formation of acid hematin which helps generate platelet aggregation and artificial clot.[,,,] It also serves as a matrix for fibrin deposition and has a mechanical tamponade effect on blood loss by swelling up and forming a gelatinous matrix.[,] In situ degradation of ORC is expected to commence within 24–48 h with complete dissolution by 4–8 weeks.[,,,,] Despite biocompatibility and resorption, occasional complications due to retained ORC have been described. These have been reported in varied sites, namely, spinal cord, brain, heart, abdominal organs, ovaries, uterus, and tooth sockets.[,,] Piozzi et al. in a recent literature review identified 38 cases of ORC retaining complications.[] However, ORC still continues to be widely used as the benefits far outweigh the potential risks.[,] The clinical presentation of retained ORC includes recurrence of symptoms due to pressure effects of mass lesion. The time of presentation after the surgical procedure varies from 2 h to 630 days, with 40% of cases diagnosed within the first year of surgery and 50% discovered after 5 years following the surgery.[,] With current imaging technology of computed tomography (CT)/magnetic resonance imaging (MRI) scans, the lesions are often virtually indistinguishable from an abscess or tumor.[,] The condition may be misleading for the unwary as ORC elicits an intensely cellular response featured by sheets of large cells with abundant granular basophilic cytoplasm and small reniform nuclei. Thus, these cells can mimic signet ring cell type of adenocarcinoma. The other differential diagnosis includes granular cell tumor and myeloma.[] The florid histiocytic response generally unaccompanied by lymphocytes, plasma cells, eosinophils, or neutrophils compounds the risk of misdiagnosis. Foreign body granulomas and residues of ORC may be noted in some cases.[] The lesional cells are positive with mucicarmine, Alcian blue, and diastase-PAS stains. IHC confirms the histiocytic nature by CD68 positivity. Lack of cytokeratin and S100 staining excludes diagnosis of carcinoma and granular cell tumor, respectively.[] A close histologic differential of histiocytic foreign body reaction is poylvinylpyrrolidone (PVP) storage disease which has been seen mainly in skin, bones, and lymph nodes. PVP was used in the past as plasma expander for trauma victims, but its use has been discontinued.[] Most complications associated with ORC reported in literature are related to an excess of the material.[] Some guidelines recommend using it sparingly, removing as much as possible after achieving hemostasis. Extreme care must be taken when applied in rigid nonextensible anatomical structures.[] If deemed necessary, only small quantity of ORC should be placed in situ and this information should both be documented in the operation notes and also conveyed to the patient.[,,,,] To conclude, florid histiocytic reaction with resultant mass lesion in response to oxidized cellulose can masquerade as malignancy. Despite its rare incidence, it is important for surgeons and radiologists to be aware of ORC-associated complications.[] Pathologists play a crucial role in recognizing the unique histologic character and in differentiating it from neoplastic entities. Declaration of patient consent 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. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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