Fine-needle Aspiration Cytology of Cutaneous Endometriosis: A Series of 17 Cases with Literature Review

Endometriosis is the presence of functional endometrial tissue outside the endometrium and myometrium, affecting approximately 8%–15% women of reproductive age-group.[ 1 ] It frequently occurs in the pelvis.[ 1 ] Extrapelvic endometriosis, though rare, has been reported in the urinary tract, gastrointestinal tract, thorax, and abdominal wall.[ 2 ] Cutaneous endometriosis, a type of extra pelvic endometriosis is a rare entity, observed in 0.5%–1% of women.[ 3 ] The most common sites include the abdominal wall, umbilicus, vulva, and extremities.[ 3 ] It mostly occurs following gynecological surgery. Rarely, can develop spontaneously without any history of local surgery.[ 3 ] Fine-needle aspiration cytology (FNAC) of endometriosis has specific cytological features and can be used as the first modality of investigation for an accurate and rapid diagnosis. Literature describing the cytology of cutaneous endometriosis is sparse due to its rarity and mainly comprises isolated case reports or small case series. This is the largest case series on the cytology of endometriosis, to the best of our knowledge.

In the present study, age ranged from 22 to 42 years with a mean age of 32 years. The maximum number of cases was seen in the third decade (10/17). The most common site was the abdominal wall with 15 (88%) cases, followed by the umbilicus and perineum with one case each. The preceding history of surgical procedures was obtained in 14/17 cases – cesarean section in 12 cases, exploratory laparotomy and episiotomy in one case each. Thus, 14 of 17 (82%) cases were related to scar, also referred as scar endometriosis while three cases were likely spontaneous. Most common symptom was swelling seen in 16/17 (94%) cases followed by cyclic pain during menstruation in 15/17 cases (88%). The duration of symptoms ranged from 1 month to 2 years. Cytology revealed two cell populations: epithelial cells, which were polygonal to columnar with round to oval nuclei, uniform chromatin and moderate amount of cytoplasm arranged in flat sheets and honeycomb pattern. Also seen were stromal fragments with hyperchromatic, round to spindle-shaped cells. Some fragments showed traversing blood vessels [ Figure 1a - c ]. The background showed many pigment-laden macrophages with cyst macrophages [ Figure 1d and e ]. Benign epithelial cells and macrophages/hemosiderophages were seen in all 17 (100%) cases and endometrial stromal cells in 11/17 (65%) cases. Decidual change and tubal metaplasia occurred in one case each. Background contained inflammatory cells in three cases. Mild nuclear enlargement with prominent nucleoli constituting epithelial atypia, was observed in 6/17 (35%) cases [ Figure 1f ]. Histopathology follow-up was available in 6/17 (35%) cases and all were concordant [ Figure 2a and b ]. (a) Benign glandular epithelial cells and stromal fragments (Papanicolaou stain, ×100). (b) Stromal cells – cellular fragments of ovoid to spindle cells with transgressing vessels (Papanicolaou stain, ×400). (c) Monolayered sheet of benign epithelial cells (Papanicolaou stain, ×400). (d) Macrophages against a dirty background (Papanicolaou stain, ×100). (e) Pigment-laden macrophages (Giemsa stain, ×400). (f) Epithelial atypia and hemosiderophages (Papanicolaou stain, ×400) (a) Gross appearance of endometrioma. (b) Endometrial glands with surrounding stroma (H and E, ×100)

A high degree of clinical suspicion for endometriosis should be made, especially in women of reproductive age group presenting with periodic symptoms and mass lesion adjacent to previous surgical scars. Careful interpretation of cytopathological features and clinical history are necessary for the correct identification of endometriosis on FNAC. There are no conflicts of interest.

Cutaneous endometriosis is often a diagnostic pitfall due to its varied clinical presentation, and lack of diagnostic radiological findings and biochemical markers.[ 4 ] It can mimic suture granuloma, hematoma, abscess, sarcoma, desmoid tumor, and metastasis.[ 4 ] It is most commonly seen in women of reproductive age, typically between 20 and 40 years.[ 5 ] The presenting complaint is usually a tender, firm, and sometimes pigmented nodule, accompanied by increasing pain and size during the menstrual period.[ 5 ] In the present study, the average age at presentation was 32 years, and 94% cases presented with swelling and 88% with cyclic pain, as observed by other authors.[ 5 6 7 8 ] The cyclical nature of symptoms is pathognomonic; however, it may not be seen with all cases. Cutaneous endometriosis usually follows a surgical procedure and is also referred to as scar endometriosis. It frequently follows cesarean section, hysterectomy, and hysterotomy.[ 6 ] Rare occurrence after episiotomy, hernia repair, laparotomy, and laparoscopic trocar site has also been reported.[ 6 ] The most common preceding surgery in our study was the cesarean section with 12 (70.6%) cases. Episiotomy and laparotomy site endometriosis each constituted one case. A review study by Horton et al . showed abdominal wall endometriosis associated with a caesarean scar and hysterectomy in 57% and 11% of cases, respectively.[ 7 ] Pathan et al . also observed that scar endometriosis more commonly affected caesarean scars than hysterectomy scars.[ 8 ] Cutaneous endometriosis can develop spontaneously without prior surgery and is often located at the umbilicus and rarely at the vulva, perineum, groin, and extremities.[ 9 ] The present study had three (17.6%) such cases and the nodules were located at the abdominal wall. Ecker et al . observed 9% (6 of 65) cases of abdominal wall endometriosis had no history of prior surgery and presented with lumps in the umbilicus and groin.[ 9 ] The patients with spontaneous onset of disease had a more severe pelvic disease compared to those with scar endometriosis.[ 9 ] FNAC of endometriosis has characteristic cytomorphological features. It demonstrates sheets of epithelial cells, stromal cells, and a variable number of hemosiderin-laden macrophages.[ 10 ] The presence of any two of the three components is diagnostic of endometriosis.[ 10 ] In the present study, epithelial cells and hemosiderin-laden macrophages were present in all the cases (100%) and stromal cells in 11 cases (65%), This was in accordance with the study by Medeiros et al . in which epithelial cells and stromal cells each were present in 86% of cases and hemosiderin-laden macrophages in all the cases.[ 5 ] The cytological features of endometriosis can vary according to cyclical hormonal changes. In the proliferative phase, bland glandular cells are seen as honeycomb sheets and in tight clusters with occasional nonatypical mitosis. During the secretory phase, the cell size gradually increases with cytoplasmic micro-vacuolations while stromal elements can develop decidual or myxoid change.[ 10 ] Epithelial cells can undergo morphological changes like squamous, mucinous, or tubal metaplasia.[ 1 8 10 ] Nuclear atypia may be seen which can result in an inaccurate diagnosis of malignant neoplasm.[ 1 8 10 ] In the present study, six cases (35.3%) showed mild epithelial atypia. Pathan et al . also observed mild to moderate epithelial atypia in three (37.5%) of the eight cases.[ 8 ] Rekhi et al . have reported a case in which the presence of cytological atypia led to an erroneous diagnosis of metastatic adenocarcinoma.[ 11 ] A cytopathologist should be aware of these variations and report cautiously with advise on biopsy for a definitive diagnosis. Other differentials, especially in the absence of stromal cells, would include cutaneous adnexal neoplasms, or mesenchymal tumors if only the stromal fragments are seen. Attention to the location, clinical history of cyclical changes and high index of suspicion will help prevent misdiagnosis. The primary approach to managing cutaneous endometriosis is surgical excision, often combined with hormonal treatment. Early diagnosis and appropriate management can improve patient outcomes.

We present 17 cases of cutaneous endometriosis diagnosed on FNAC over 12 years (January 2013–December 2024). FNAC was done by standard technique. Air-dried and wet fixed smears were prepared and stained with Giemsa and Papanicolaou stains, respectively. Cytomorphological features were analyzed and correlated with clinico-radiological findings and histopathology, where available.