Small intestinal perforation secondary to metastasis from skin squamous cell carcinoma: A case report and literature review

Abstract

Introduction and importance

Primary and metastatic carcinoma of the small intestine are rare. While most of these malignancies are adenocarcinomas, squamous cell carcinoma (SCC) of the gastrointestinal tract is uncommon. We present a case report of a rare occurrence of skin SCC metastasizing to the ileum, highlighting diagnostic challenges and clinical implications.

Case presentation

An 83-year-old female had a history of cutaneous SCC excision in the right temporal region two years prior to the current emergency department visit, followed by metastatic recurrence in a right intra-parotid lymph node treated with radiotherapy. The patient exhibited septic shock and an acute abdomen, and an abdominal computed tomography scan revealed signs of intestinal perforation. Emergency exploratory laparotomy confirmed purulent peritonitis and perforation of the terminal ileum. Subsequently, a 20 cm intestinal resection was performed. Histopathological examination of the resected specimen revealed a 4 cm perforated SCC of the small intestine (pT4 pN0 L0 V1 Pn0 R0).

Clinical discussion

Metastases of the small intestine are rare. The primary sites for these metastases are typically the uterus, cervix, colon, lung, breast, or melanoma. SCC of the small intestine is particularly rare and poses challenges in diagnosis owing to non-specific symptoms. The prognosis for SCC of the small intestine is generally poor, and the potentially aggressive behavior of some skin SCC emphasizes the need for increased awareness and vigilance in managing such cases.

Conclusion

This case report underscores the importance of considering metastatic disease in the small bowel of patients with a history of skin SCC who present with new-onset abdominal symptoms.

Highlights

• •Rare case of small bowel perforation caused by metastasis of cutaneous squamous cell carcinoma (cSCC).
• •SCC of the small bowel is a diagnostic challenge due to nonspecific symptoms.
• •Increased attention and vigilance is key in effective management of such cases.

1. Introduction

Intestinal perforation is a life-threatening condition that is commonly encountered in visceral surgery. The primary treatment approach involves emergency surgery, including damage control surgery or intestinal resection with definitive repair. The leading causes of perforation in industrialized countries are bowel obstruction and inflammatory bowel disease whereas infectious causes of intestinal perforations are more common in developing countries [1]. Early recognition and prompt treatment are crucial to prevent the high mortality rates associated with peritonitis. The most common malignancies found after histopathologic examination of perforated small bowel specimens include lymphoma, leiomyosarcoma, gastrointestinal stromal tumor (GIST), adenocarcinoma, and metastatic carcinomas of the hypopharynx, cervix, and lung [2].

Primary and metastatic squamous cell carcinomas (SCC) of the small intestine are extremely rare. Fewer than 30 cases of primary SCC of the small intestine have been reported in the literature. Although there are few references of SCC metastasis in the small intestine, only in four case reports, the skin is the primary site [[3], [4], [5], [6]].

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer after basal cell carcinoma (BCC) [7]. Early diagnosis and treatment of cSCC generally lead to an excellent prognosis [8]. A recently published epidemiologic cohort study suggested that the incidence rate of cSCC continues to increase, especially among female patients. Furthermore, the occurrence of multiple cSCCs in a single patient significantly contributes to the current and future burden on dermatologic healthcare, which requires additional resources for diagnosis and treatment [9].

Herein, we present an extremely rare case of a patient admitted to Cantonal Swiss Hospital in an emergency setting with ileum perforation, identified as a metastasis of cSCC through histopathological examination. The case report was conducted in accordance with the SCARE (Surgical CAse REport) criteria [10].

2. Case presentation

An 83-year-old woman was transported to the Emergency Department by ambulance because of worsening abdominal pain, hematochezia, and asthenia that had been present for several weeks. The detailed history revealed one episode of hematochezia two days before admission and abdominal pain for the last 5 days.

Her personal medical history was marked 2 years prior to the current emergency department visit by a total excision of cutaneous squamous cell carcinoma (cSCC) in the right frontotemporal region, staged as pT1 uN0 cM0 G2. The tumor extended into the subcutis, the greatest vertical tumor thickness was 5 mm, the lateral extension <2 cm and the excision margin >5 mm (R0). One year later, she presented with a recurrence of squamous cell carcinoma in the metastatic form of the right parotid gland. Radiation therapy was initiated and was well tolerated. Subsequent sonography and CT follow-up revealed a persistent heterogeneous lesion within the right lobe of the right parotid gland, which was suspected of either recurrence or post-radiation alterations. Furthermore, a rounded hypodense structure of 3 cm in the pelvic cavity and in contact with the small intestine showed in the CT scan was difficult to interpret because of artifacts due to prosthetic material of the right hip. No further investigations were conducted regarding these findings, and a clinical and radiological follow-up of 3 months was decided. Chronological events associated with this disease are summarized in Fig. 1.

Fig. 1.

Course of events related to cSCC.

The patient also had a history of insulin-dependent type 2 diabetes, hypertension, rhythmic and valvular heart disease, chronic renal failure (KDIGO stage G3a), and polymyalgia rheumatica. Her surgical history included cholecystectomy for symptomatic cholelithiasis, hysterectomy for heavy monthly bleeding, oophorectomy for a benign ovarian cyst, and minor orthopedic surgeries.

Her current medication consisted of metoprolol, apixaban, and prednisone 5 mg once daily.

In the clinical setting, the patient's initial vital signs revealed a low blood pressure of 85/35 mmHg in both arms, and a regular pulse rate of 66 beats per minute. Physical examination revealed guarding and rebound tenderness of the lower abdomen. The digital rectal examination was unremarkable, with an empty rectal ampulla, and no blood was found.

Laboratory tests showed a plasma creatinine level of 240 umol/l, white blood cell count of 15 G/l, hemoglobin level of 86 g/l, C-reactive protein level of 68 mg/l and hyperlactatemia of 4.5 mmol/l.

An abdominal CT scan without contrast revealed numerous extraluminal air bubbles, fat stranding opposite the right colonic angle, and intra-abdominal free fluid, compatible with intestinal perforation (Fig. 2). The location of this lesion corresponded to that identified on the CT scan performed three months earlier after the completion of radiotherapy (Fig. 3).

Fig. 2.

Subject to hardening artifacts of the right hip prosthesis, presence of a pelvic mass, with foamy content and suspicion of fistula with a small bowel loop (white arrow) on CT-Scan.

Fig. 3.

CT-Scan of a round hypodense structure (∼3 cm) in the pelvic area (white arrow), in contact with the small bowel, subject to artifacts from the prosthetic material.

The patient was promptly resuscitated with fluids and received high-dose proton pump inhibitor (PPI) therapy (80 mg bolus followed by 8 mg/h) and antibiotic treatment (piperacillin-tazobactam). Blood cultures were collected for further analyses.

An emergency exploratory laparotomy revealed generalized purulent peritonitis. Approximately 20 cm from the ileocecal valve, a short loop of the ileum with a 4 cm perforation in the middle was identified, surrounded by local fecal peritonitis (Fig. 4). Abdominal exploration revealed no macroscopic peritoneal or hepatic metastases. Segmental resection of the affected ileum (20 cm) was performed. Due to intraoperative hemodynamic instability and considering the patient's comorbidities, medication, and suspected malignancy, a damage control surgical approach was decided, and the two intestinal stumps were left closed intra-abdominal. A second-look laparotomy was scheduled within 24–48 h.

Fig. 4.

Ileal perforation.

Small bowel tissue was sent for histological analysis and reported an approximately 4 cm (∼ 1.5 in) outbreak of a non-keratinizing squamous cell carcinoma, acantholytic variant, P16[−], in the small intestinal wall, which was perforated and associated with fibrinoleukocytic peritonitis. Other findings included the presence of venous invasion and one lymph node identified in the mesenteric adipose tissue without malignancy.

Blood cultures obtained before surgery were positive for Klebsiella pneumoniae. The peritoneal fluid collected during the operation showed positive results for Klebsiella pneumoniae, Escherichia coli and some species of Bacteroides, such as Bacteroides sp., Bacteroides thetaiotaomicron, and Bacteroides vulgatus.

The patient was admitted postoperatively to the Intensive Care Unit. She suffered from severe septic shock and underwent aggressive fluid resuscitation, continuous norepinephrine support up to 0.5 micrograms/kg/min., broad-spectrum antibiotic (Piperacillin-Tazobactam followed by Meropenem) and corticoid administration. Despite this treatment, the patient remained in shock, requiring high norepinephrine doses. Because of the severity of the illness and the expressed wishes of the patient, as reported by her relatives, it was decided not to pursue further treatment, and a second-look laparotomy was not performed. The patient peacefully died shortly thereafter.

3. Discussion

Primary and metastatic carcinomas of the small bowel are rare, with an incidence of approximately 2 in 100,000 individuals [11]. Metastases account for approximately 10 % of cases, most often arising from primary tumors in the uterus, cervix, colon, breast, lung, or melanoma. In most cases, primary malignancies are adenocarcinomas [12]. Squamous cell carcinoma (SCC) of the small bowel, either primary or metastatic, is rare. Interestingly, only four case reports have documented skin as the primary site of secondary tumors of the small intestine [[3], [4], [5], [6]]. They are summarized in Table 1.

Table 1.

Overview of the reviewed sources.

Author	Year	Patient demography	Primary localisation	Metastasis localisation	Complication	Outcome
N. Hitchen et al.	2016	70-year-old woman	Back	Jejunum	Perforation with peritonitis	Death 8 weeks after surgery
R. Li et al.	2014	71-year-old man	Hand	Ileum	Small bowel obstructions	Death 4 months after surgery
B. Schwartz et al.	2016	65-year-old male	Chest	Jejunum	None	n.e.
H. Zheng et al.	2010	53-year-old man	Scalp	Jejunum	Perforation with peritonitis	Death 7 months after surgery

Cutaneous squamous cell carcinoma (cSCC) is characterized by the abnormal and accelerated growth of squamous cells [7,8]. Although in the greater part it has a good prognosis and low rates of metastasis, there are certain risk factors and features associated with more aggressive behavior [7]. Gastrointestinal involvement in cSCC is extremely rare and metastasis is believed to occur primarily via lymphatic spread. Secondary lesions found in the small bowel indicate an advanced stage and poor prognosis. Furthermore, when they manifest with a complicated course such as perforation, mortality is even higher [13,14].

Overall, small-bowel malignancies have a poor prognosis, partly due to frequent delays in diagnosis, as symptoms are mainly vague and nonspecific. Acute presentations vary, including obstruction, intussusception, bleeding, or perforation. Furthermore, even under the suspicion of a secondary small-bowel lesion, radiologic detection is difficult. Different modalities, such as small-bowel endoscopy, contrast studies, and CT scans, can be helpful. However, only 18F-2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG PET)/CT and capsule endoscopy have shown some early success in the diagnosis of small-bowel metastatic tumors [4,15].

In cases of primary or secondary SCC bowel lesions, surgical treatment is a validated approach and may be unavoidable in emergencies. Wide local surgical resection of the tumor and lymph node-bearing mesentery could be considered the surgical treatment of choice. However, in the case of secondary lesions or in an emergency setting, which corresponds to an advanced stage disease, surgical treatment has a palliative role, and complex resections are not recommended. In both cases, the outcome was poor.

Although the majority of patients with cSCC present an excellent prognosis after adequate surgical resection, a subset of patients carry an increased risk of lymph node metastasis, local recurrence, and disease-specific death [7,9,14]. High-risk features include tumor diameter ≥ 2 cm, tumor thickness ≥ 2 mm, anatomic tumor site (face, ear, pre/post auricular area, genitalia, hands, and feet), poor histological differentiation, certain histological subtypes, evidence of perineural invasion, immunosuppression, and the presence of parotid metastases [3,7,16].

In our case and in concordance with the literature, our patient presented with an aggressive form of cSCC, the acantholytic variant, which had already led to parotid and level II lymph node metastases soon after the primary diagnosis and surgical treatment. Furthermore, immunosuppression, with great mention to transplant patients, should always be considered, presenting a higher risk of both cSCC development and a worse disease course [2,10]. Our patient was in long-term medical treatment with corticoids because of rheumatic polymyalgia, probably contributing to a more aggressive tumor behavior but also influencing to a certain degree, along with the patient's hemodynamic instability, emergency surgical treatment, and the decision to perform a damage control surgery without proceeding to anastomosis creation.

Finally, we would like to outline the difficulty in detecting these secondary small bowel lesions, firstly because of their rarity and because they lack specific characteristics, they often remain unidentifiable until they reach an advanced stage or become complicated [12]. In our case, the diagnosis of metastatic cSCC was confirmed only after pathological examination results were obtained. Additionally, it is noteworthy that a previous follow-up CT scan described a round hypodense structure of approximately 3 cm in the pelvic area, in contact with the small bowel, but it was not interpreted due to artifacts from the prosthetic material in the right hip (Fig. 3). The examination was carried out in a patient believed to have a total response to radiotherapy. These facts, together with the rarity of a small intestinal metastasis from a cSCC, did not lead to further investigations. It further highlights the challenges in diagnosing these lesions and raises questions about the need for further screening and investigation, even in the presence of nonspecific and rare findings in otherwise nonaggressive tumors that rarely metastasize to the abdominal cavity.

There are only four case reports in the literature concerning secondary cutaneous SCC of the small bowel [[3], [4], [5], [6]]. Known as a disease of late adulthood, with the exception of appearance at a younger age in immunocompromised patients, in these four case reports, the youngest patient was 53 years old and the oldest was 71 years old. It is of great interest that, as in our case, three of these four patients were treated surgically in an emergency setting without their metastatic small bowel SCC being already known. Bowel perforation was the cause in two cases and obstruction in the one. In the last case, the small bowel lesion was incidentally found preoperatively during elective sigmoid resection because of an already proven cSCC metastasis in a colonic diverticulum. However, in one of these four cases, perforated metastatic small bowel SCC was the first acute presentation of the disease, resulting in further investigations and subsequent detection of the primary cutaneous site. Of the four cases, only one small bowel metastasis was located in the ileum, while all three others were identified in the jejunum. All patients were treated surgically and small bowel resection was performed. In three case reports, the outcome was poor, with death occurring 8 weeks to 7 months post-operatively. In only one case, the last follow-up, six months after the operation, did not show any other metastatic disease or recurrence. All four case reports stress the rarity of metastatic small bowel cSCC and their presentation usually in an emergency setting with poor prognosis.

4. Conclusion

Most cases of cSCC are limited to the skin and are successfully managed with local therapy. However, distant metastases occur with an annual incidence in up to 4 %, leading to increased mortality [7]. Therefore, early diagnosis and detection are important. However, non-specific symptoms and imaging findings, as well as the lack of awareness of this very low but existing proportion of tumors, result in a considerable delay in diagnosis and a poor outcome. Surgeons should be alerted in cases of acute abdominal pain or no specific abdominal symptoms when there is a history of cancer, even in cases where the primary tumor rarely metastasizes in the gastrointestinal tract.

However, as the incidence of cSCC continues to increase [8,9], these rare metastatic sites might also become more apparent, making awareness of this entity even more important.

Increased awareness, vigilance, and comprehensive evaluation are key to identifying this subset of cases and providing timely interventions for improved patient management, in light of the growing prevalence of SCC.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This study involves human participants but was not approved by an Ethics Committee(s) or Institutional Board(s).

Our institution does not require ethical approval for reporting individual cases or case series.

Funding

All authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Guarantor

The guarantor for this statement is Dr. med. Maxence Emmanuel Reynard. He can be reached at any time under reynard.maxence@gmail.com.

Registration of research studies

This study is not a “First in Man” study.

CRediT authorship contribution statement

All authors contributed to the design, data collection, analysis and interpretation of this protocol. All authors contributed read and approved the final manuscript.

Declaration of competing interest

All authors declare no competing interests.

Data availability

Dataset will be available from the corresponding author at reynard.maxence@gmail.com. The presented data are anonymised and risk of identification is low.