Cytopathological features of scar endometriosis mimicking an adenocarcinoma: A diagnostic pitfall.

Scar endometriosis can be a diagnostic challenge in fine-needle aspiration cytology (FNAC) smears that at times, is the first diagnostic modality in such cases. The challenge is amplified when the clinical details are limited and cytopathological features reveal nuclear atypia. A 33-year-old lady presented with an abdominal swelling that she noticed after she met with a scald. Clinically, the swelling was located lateral to her 3-year-old pfannenstiel incision scar. The initial diagnosis on FNAC was metastatic adenocarcinoma. On review, smears were hypercellular, comprising epithelial cells in groups and focally, regular glandular arrangements, imperceptibly admixed with numerous, relatively smaller, short spindly cells. Epithelial cells exhibited mild to focally, moderate nuclear enlargement/atypia. Subsequent biopsy and excision revealed endometrial glands exhibiting focal nuclear atypia with adjacent stroma. Diagnosis of endometriosis was offered. The results were reinforced with positive estrogen receptor staining in the glands and stroma, along with CD10 positivity in the stroma. The patient was recommended gonadotropin releasing hormone analogs and is presently free of disease a year after her diagnosis. FNAC can be a pitfall in the diagnosis of endometriosis. Correct diagnosis has significant therapeutic implications. Although presence of atypia in such cases should not delude the diagnosing cytopathologist for consideration of endometriosis, it should be documented. The value of clinical history in such cases cannot be overemphasized.

Introduction

Endometriosis is defined as the presence of ectopic, functional endometrial tissue outside the endometrium and myometrium and affects approximately 10-15% women in the reproductive age-group.[1] Endometriosis can occur at intra- and extrapelvic locations with abdominal wall as a site in 0.5-1% cases of pelvic endometriosis.[2]

Although it is fairly diagnosed on an adequate biopsy specimen, based on the presence of any two of the three histological components, including endometrial glands, stroma and macrophages, a challenge occurs of diagnosing endometriosis on a fine needle aspiration cytology (FNAC) that at times, becomes the first diagnostic modality in such cases, especially when the available clinical details are limited and some of the cytological features are atypical. Cutaneous endometriosis is a recognized diagnostic pitfall on cytological smears.[3] In a documented series of 10 cases of abdominal endometriosis, diagnosed by FNAC, malignancy was suspected in two.[4] Herein, we present a case of cutaneous endometriosis occurring in the abdomen, mimicking adenocarcinoma on FNAC.

Case Report

This was a case report of a 33-year-old, non-obese, Asian, lady physician, P1, A0 sustained a minor scald over her right inguinal region. The scald was adjacent, but not involving the right lateral aspect of her 3-year-old Pfannenstiel incision scar. The wound completely re-epithelialized within 10 days, leaving behind slight skin discoloration. A month later, she noticed a “thumb-sized” swelling in the same area. She had a normal menstrual history.

Clinically, the swelling was superficial to abdominal muscles and measured 2 cm; was non-tender, non-inflammatory, firm and mobile. She underwent FNAC, followed by incisional biopsy and excision.

Laboratory investigations

The patients’ serum tumor marker levels, including celomic antigen (CA) 125, carcino embryogenic antigen and CA 19.9 were within the normal range.

Radiological findings

Her abdominal and pelvic ultrasonogram revealed a 3 cm sized subcutaneous, hypoechoic, solid mass with scattered internal echoes.

Magnetic resonance imaging (MRI) showed a heterogeneous subcutaneous soft tissue mass measuring 3 cm × 2.5 cm × 2 cm. The lesion was hypointense on plain T1-weighed images, hyperintense on T2-weighed and short inversion time recovery axial images. Post-contrast T1-weighed images showed heterogeneous enhancement within the lesion [Figure 1].

Figure 1

Magnetic resonance imaging findings. (a) Short inversion time recovery axial image showing hyperintense lesion in area of surgical scar (arrow). (b) Post-contrast T1-weighed Sagittal view showing heterogeneous enhancement within the lesion (arrow)

Cytopathological findings

On review, Hematoxylin and Eosin (H and E), as well as Giemsa stained smears were hypercellular and revealed epithelial cells in groups and glandular architecture, imperceptibly admixed with numerous, relatively smaller, short spindly cells. Epithelial cells exhibited mild to focally, moderate nuclear enlargement. Interspersed were metaplastic cells against a hemorrhagic background [Figure 2]. Whereas the initial diagnosis offered was a metastatic adenocarcinoma, on review, endometriosis was suggested.

Figure 2

Cytopathological findings. (a) Hypercellular smear showing glandular cells (arrows) intimately admixed with short spindle shaped stromal cells (H and E, ×200). (b) Glands with smooth contours, stromal cells and blood vessels (H and E, ×200). (c) Focal metaplasia (H and E, ×400). (d) Higher magnification displaying epithelial cells exhibiting nuclear enlargement and discernible nucleoli (Giemsa, ×400)

Histopathological findings

Incisional biopsy revealed fibrocollagenous tissue and few glands exhibiting focal nuclear atypia that was interpreted as dysplasia.

Excision specimen measured 5.5 cm × 4.5 cm × 2.5 cm with an overlying skin that showed a linear scar. On serial sectioning, a firm nodule was identified in the subcutaneous region measuring 1.3 cm × 0.5 cm × 0.4 cm. Cut surface of the nodule was grey-white with focal areas of hemorrhage.

Conventional H and E stained microsections showed glandular structures, exhibiting focal dilatation, surrounded by stromal cells, indicative of endometrial tissue with focal inflammation and metaplasia. Epithelial cells exhibited focal atypia. However, there was insufficient atypia to label it as an adenocarcinoma. Diagnosis of endometriosis was offered. Immunohistochemically, the glands were diffusely positive for estrogen receptor and progesterone receptor while the stroma was diffusely positive for CD10. Diagnosis of endometriosis was reinforced [Figure 3]. All the resection margins were free of the lesion.

Figure 3

Histopathological findings. (a) Initial biopsy revealing a gland within stroma exhibiting atypia (H and E, ×200). (b) Excision specimen displaying variable dilated endometrial glands with interspersed stroma (H and E, ×100). (c) Focal atypia within endometrial gland (H and E, ×400). (d) Diffuse estrogen receptor positivity within glands and stroma (diaminobenzidine (DAB), ×400). (e) Diffuse CD10 positivity highlighting the stroma (DAB ×400)

Post-surgery, patient is on gonadotropin releasing hormone analogues; is currently free of disease since 12 months and is on follow-up.

Discussion

Most cases of cutaneous endometriosis have been known to have occurred in the surgical scars.[5] The incidence of endometriosis associated with cesarean incisions has been reported to be up to 1% (most commonly, 0.03-0.4%).[6] There has been an increase in cases of endometriosis after laparoscopic surgeries.[7]

The imaging features in such cases are non-specific, except for site and extent of the lesion that can be accurately delineated by MRI, as noted in the present case. Ultrasonogram is helpful in identifying whether the lesion is solid or cystic. Whereas the definite diagnosis of cutaneous endometriosis is made on a sizable biopsy, there is documentation on cytomorphological features of cutaneous endometriosis, considering FNAC, in view of being a relatively safe, inexpensive and non-invasive procedure in present time's forms as one of the first tests for diagnosis and triage of such cases.[23478] While most of these studies have addressed prospective or retrospective analysis of cytopathological spectrum of endometriosis, only rarely diagnostic challenge, in terms of cases suspected with malignancy, has been addressed.[34]

In the present case, presence of cytological atypia led to an erroneous initial diagnosis of a metastatic adenocarcinoma and on the subsequent biopsy, glandular dysplasia was suspected. There was no history relating to appearance or increase in size of the swelling with menstrual cycle that otherwise, is a suggestive clinical history in such cases. After the access of the history of an earlier cesarean section scar, endometriosis was considered that was confirmed on wide-excision. The results were further reinforced with immunohistochemical stains. In the excision specimen, focal atypia was identified. A study by Kazakov et al.[5] have addressed presence of atypia and variety of metaplasia in cases of scar endometriosis. The present case is one of the few displaying atypia and metaplasia in endometriosis that constituted as a diagnostic pitfall.[24] While atypia should not delude a cytopathologist from consideration of endometriosis, it should be documented and such cases may be followed up. Malignant change of scar endometriosis is rare. Only 21.3% of cases of malignant transformation of endometriosis occur at extragonadal pelvic sites and 4% in laparotomy scars.[9]

With regards to pathogenesis, two proposed theories of scar endometriosis include hematogenous, lymphatic or direct implantation of endometrial tissue through surgical manipulation, or regurgitation of menstrual blood during menstruation and primitive pluripotent mesenchymal cells undergoing endometrial differentiation and metaplasia.

Therapeutically, wide excision is the treatment of choice in such cases. Our patient is presently free of disease since a year and is on follow-up. To sum up, FNAC is a safe and effective tool for identification of endometriosis and can obviate the need for diagnostic surgical procedures. Moreover, it can save the patient from undergoing radical treatment. Clinical history and careful interpretation of cytopathological features are necessary for developing an index of suspicion for correct identification of endometriosis over an adenocarcinoma on FNAC. Atypia within the glandular epithelium of endometrioid lesions should be documented and such patients should possibly be followed-up after a wide-excision of their lesion.