From endometrium to fingernail bed: histological evaluation of a rare cutaneous metastasis

Abstract

In the dermatological spectrum of oncologic manifestations, cutaneous metastases from endometrial carcinoma stand as a rarity, given the tumour’s predilection for neighbouring uterine regions. We present an exceptional case of a patient in her mid-50s, whereby an endometrial carcinoma, defying conventional pathways, manifested on the skin and nail of her distal fourth finger, an unusual site for cutaneous metastases, with a specific histology of the primary cancer.

Background

Cutaneous metastasis has significant clinical implications. Often, the presence of cutaneous metastatic lesions indicates an advanced stage of an underlying malignancy. It can serve as the initial manifestation of visceral cancer, leading to the diagnosis. Endometrial carcinoma is one of the most commonly diagnosed gynaecological malignancies, primarily affecting postmenopausal women. It is most often characterised by the proliferation of malignant glandular epithelial cells within the endometrium. While its metastatic progression frequently involves adjacent tissues, it can also involve distant organs such as the lungs, liver and bones.^1–4 Previous literature has documented metastases to the skin in locations such as the shoulder, leg, abdomen and vagina; however, to our knowledge, there have been no reported cases of cutaneous metastases to the digits (table 1).

Table 1.

Overview of documented cases highlighting cutaneous metastasis stemming from endometrial carcinoma

Case reference	Age (years)	Location of metastasis	Histopathology diagnostic methods (H&E/IHC)	Treatment and follow-up	Post-treatment survival
Bashline et al2	62	Abdominal hysterectomy scar	H&E: dermal proliferation of atypical glandular epithelium with diffuse haemorrhage IHC: CK7.	External pelvis RTX+CTX (etoposide+cisplatin)	5 months
Bhutani5	62	Anterior left shoulder	H&E: neoplastic cells arranged in groups, sheets and acinar structures; moderately pleomorphic nuclei; coarse nuclear chromatin; vacuolated cytoplasm FNAC histology was diagnostic. IHC: not completed.	CTX (carboplatin/taxol)+whole pelvis radiation	3 months
Ma et al3	60	Lower leg and vagina	H&E: moderately differentiated endometrial adenocarcinoma with significant invasion. IHC: not completed.	TAHBSO+pelvic and para-aortic lymphadenectomy with peritoneal washing+CTX (docetaxel+cisplatin)+5FU (vaginal orifice injections)	11 months
Atallah et al9	62	Laparotomy site with vulva extension	H&E: endometrioid adenocarcinoma IHC: not completed.	TAHBSO+pelvic lymphadenectomy+CTX (etoposide+cisplatin)	3 years
Giordano et al12	66	Vulvar posterior commissure	H&E: endometrioid adenocarcinoma IHC: CA-125	TAHBSO+selective pelvic lymph node sampling+hormone therapy	8 months
Baydar et al13	58	Initial operation site	H&E: endometrioid adenocarcinoma IHC: not completed.	RTX+CTX	Died after two cycles CTX
El M’rabet et al14	72	Trunk, extremities and scalp	H&E: endometrioid adenocarcinoma IHC: CK7, PTEN, ER and PR	TAHBSO+pelvic and para-aortic lymph node sampling	2 weeks
Fan et al15	54	Breast	H&E: endometrioid adenocarcinoma IHC: CK7, P16 and P53	No information available	7 months
Stonard nd Manek16	73	Left lower leg	H&E: endometrioid adenocarcinoma IHC: ER and PR	TAHBSO+CTX+immunotherapy+hormone therapy	No information available
Nienhaus et al17	51	Umbilicus	H&E: endometrioid adenocarcinoma IHC: not completed.	Hysterectomy/abdominal adnexectomy with excision of the navel+pelvic and para-aortic lymphadenectomy+CTX+immunotherapy+hormone therapy	13 years
Our case	Mid-50s	Left fourth distal finger and nail bed	H&E: endometrioid adenocarcinoma IHC: CK7, PAX8, ER and PR	TAHBSO+pelvic and para-aortic lymphadenectomy+CTX+immunotherapy+hormone therapy	6 months

The average age of the cohort is 60.2 years, with a post-treatment survival span ranging from a minimal 2 weeks up to a maximum of 13 years. The average post-treatment survival span was approximately 1 year and 11 months (22.85 months). Key surgical and therapeutic interventions referenced in the table include TAHBSO, RTX and CTX, H&E and IHC. All listed IHC results indicated were positive.

CK7, Cytokeratin-7; CK125, Cytokeratin-125; CTX, chemotherapy; ER, Estrogen Receptors; FNAC, fine needle aspiration cytology; 5FU, Fluorouracil; IHC, immunohistochemistry; PAX8, Paired-box gene-8; PR, Progesterone Receptors; PTEN, Phosphatase and tensin homolog; RTX, radiotherapy; TAHBSO, total abdominal hysterectomy with bilateral salpingo-oophorectomy.

Case presentation

A woman in her mid-50s was evaluated for a 3-week history of a rapidly growing, painful nodule on the distal fourth finger, accompanied by nail discolouration. Physical examination revealed a 1.4 cm violaceous, firm nodule on the dorsal aspect of the left distal fourth finger (figure 1). The adjacent nail showed onycholysis and discolouration. No other suspicious cutaneous lesions were noted, and the patient had no other metastases.

Figure 1.

A clinical manifestation of our case of cutaneous metastasis originating from endometrial carcinoma. The patient presented with a violaceous, firm nodule on the dorsal aspect of the left distal fourth finger. The adjacent nail showed onycholysis and discolouration.

Investigations

A shave biopsy of the nodule was performed, which revealed malignant glandular epithelial cells and stroma, consistent with endometrial morphology (figure 2). Further investigation revealed that the lesion was positive for CK7 (Cytokeratin 7), PAX8 (Paired Box Gene 8), ER (Estrogen Receptor) and PR (Progesterone Receptor), WT1 (Wilms Tumor-1) and was negative for CK20 (Cytokeratin 20) (figure 3). Further imaging, including a CT scan of the abdomen and pelvis, showed a mass in the endometrial cavity with invasion into the myometrium without any other distant metastasis. The histopathological findings, including immunohistochemistry of the primary endometrial carcinoma, resembled the metastasis.

Figure 2.

H&E stained sections of the lesion, showing the dermis infiltrated by atypical glands.

Figure 3.

The lesion is highlighted by CK7 (Cytokeratin 7), PAX8 (Paired Box Gene 8), WT1 (Wilms Tumor-1), ER (Estrogen Receptor) and PR (Progesterone Receptor) and was negative for CK20 (Cytokeratin 20), consistent with metastatic endometrial carcinoma.

Differential diagnosis

Based on the clinical, histopathological and radiological findings, a diagnosis of stage IV endometrial carcinoma with cutaneous metastasis to the skin and nail bed of the distal fourth finger was made.

Treatment

The metastatic lesion was excised, and the patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. Additionally, she received systemic treatment with a combination of chemotherapy, hormonal therapy and targeted therapy with carboplatin, paclitaxel and bevacizumab (an antivascular endothelial growth factor agent). She is responding well to chemotherapy and is under close surveillance with regular imaging and clinical assessments.

Outcome and follow-up

The patient recovered well after surgery, and she underwent a comprehensive, systematic treatment plan. A follow-up period of 6 months of close surveillance with regular imaging and clinical assessment did not show any other distant metastasis, and the patient is responding well to treatment.

Discussion

Endometrial carcinoma typically follows a predictable metastatic pattern, with the pelvic and para-aortic lymph nodes being common sites of metastasis.⁵ The spread of endometrial cancer to the finger may have occurred through either lymphatic spread or haematogenous spread. Beginning in the endometrium, the cancer cells can invade the myometrium to come into contact with blood vessels and lymphatics. The cells can then enter the pelvic and para-aortic lymph nodes through the lymphatic system.⁵ From the lymph nodes or directly from the primary tumour, cancer cells can intravasate into the blood vessels. Once in the bloodstream, the tumour cells circulate throughout the body. They can then extravasate or exit the bloodstream at distant sites.⁶ After extravasation, tumour cells can colonise new tissue, in this case, the skin and nail bed of the finger.⁷ Certain tumours exhibit a tropism for specific tissues; molecular interactions between tumour cells and the microenvironment of the metastatic site might play a role in this selective colonisation.^{6 8} Additionally, factors such as tumour-induced immunosuppression could contribute to this phenomenon.⁷

Metastasis in such distal regions raises clinical suspicion of widespread dissemination of cancer cells. It underscores the importance of a thorough clinical examination, even in seemingly unrelated areas. Moreover, such an atypical presentation can pose diagnostic challenges, emphasising the need for a high index of suspicion and prompt histopathological evaluation.

Endometrial cancer with cutaneous metastasis would be considered an International Federation of Gynaecology and Obstetrics stage IV lesion. A recent Surveillance, Epidemiology and End Results database study of 3878 patients with metastatic endometrial cancer demonstrated that the tumour stage had the greatest impact on the adverse prognosis of patients with metastatic endometrial cancer.¹ As such, the prognosis of these patients is typically poor due to the widespread dissemination of the primary tumour. Prior literature has demonstrated that patients with such metastases have a reported life expectancy of 4–12 months following diagnosis.^{8 9} However, with timely and appropriate interventions, life expectancy can potentially be enhanced.¹⁰ All known cases, to our knowledge, are summarised in table 1. The diverse presentations and outcomes highlight the need for a high index of suspicion and comprehensive management in such cases.

Surgical excision of the cutaneous metastasis can provide symptomatic relief, especially if it is painful or functionally impairing. Additionally, localised radiation can be considered for palliation. Given the disseminated nature of the disease, systemic therapies, including chemotherapy with drugs such as paclitaxel and carboplatin, hormonal therapy or targeted agents, should be evaluated based on the tumour’s molecular profile and the patient’s overall health status.^{10 11}

Early detection of metastases is imperative to improving patient outcomes and treatment options. As such, it is imperative to differentiate between cutaneous metastases and other histological mimickers. Some of these include digital papillary adenocarcinoma, metastatic breast carcinoma, metastatic gastrointestinal adenocarcinoma, basal cell carcinoma with adenoid features, sebaceous carcinoma, mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and Merkel cell carcinoma with glandular differentiation.^12–17 Moreover, metastatic ovarian carcinoma, thyroid carcinoma or clear cell carcinoma of the urinary bladder might also be considered.

In addition to the distinct morphology of each of the previous differential diagnoses, immunohistochemical staining can help guide the final diagnosis. In our case, using CK7, PAX8, ER, PR, WT1 and CK20 with the morphology was crucial to point to the endometrial origin. Alternatively, fine needle aspiration cytology and liquid-based cytology may be considered instead of biopsy in terminally ill patients.^{10 18} Progression should be monitored in these patients through many screening processes, including regular imaging and routine clinical assessments.

Patient’s perspective.

‘When I first saw the lump on my finger and the way my nail was changing, I didn’t think much of it. Maybe a bug bite or a small injury, I thought. But it started to hurt and kept getting bigger, so I knew I had to see a doctor. Finding out it was my endometrial cancer that had spread all the way to my finger was a shock. I have never heard of anything like this before. It felt so strange and scary, especially because the doctors said it was pretty rare. It’s a lot to take in, and sometimes I feel really tired and worried about what’s going to happen next. But the doctors are keeping a close eye on me, and I am going to move forward with treatment, which makes me feel a bit better. Right now, I am just taking each day as it comes. I’m trying my best to stay positive and hope for the best.’

Learning points.

• Endometrial carcinoma usually metastasises to the gynaecological sphere but can rarely metastasise to the fingers.

• This unusual presentation serves as a poignant reminder of the disease’s aggressive nature and the potential for widespread dissemination.

• The unpredictable nature of cutaneous metastasis to distal sites necessitates a rigorous and expansive clinical evaluation for patients.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).