Cutaneous metastasis of signet ring cell appendiceal adenocarcinoma: a herald of disease recurrence

INTRODUCTION

Signet ring cell carcinomas, frequent in the stomach and intestine, are adenocarcinomas with mucus-producing tumor cells. Signet ring cell appendiceal adenocarcinoma (SRCAA) is a rare entity with poor prognosis and high tendency for metastasis to pelvic lymph nodes, ovaries, and peritoneal surfaces.^1-6 Despite numerous reports of intra-abdominal metastasis, there have been few reported cases of cutaneous SRCAA metastasis.⁵ We report a rare case of SRCAA metastatic to the cutaneous abdominal wall in a 67 years old female, which was first presenting sign of disease recurrence.

CASE REPORT

A 67 years old female with a history of stage IV signet ring cell appendiceal adenocarcinoma (SRCAA) presented with an erythematous, malodorous, tender eruption extending from her anterior abdominal wall scar that had been locally spreading over the past 3 months. In 2017, the patient had been initially treated with colectomy with ileostomy, and six cycles of leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX), followed by hyperthermic intraperitoneal chemotherapy (HIPEC). The patient had recurrence and metastatic deposits in her anterior abdominal scar prompting another seven cycles of leucovorin calcium, fluorouracil, and irinotecan (FOLFIRI), followed by radiation to the anterior abdominal wall scar in early 2018. Interval CT and positron emission tomography (PET) scans had remained negative for metastatic disease in the visceral organs, peritoneum, and lymph nodes. Her primary care physician had treated her abdominal rash with a combination of antiviral and antibiotics without improvement.

Upon presentation, physical examination was notable for edematous, erythematous, malodorous nodules coalescing into plaques on the anterior abdomen in the region of her anterior abdominal surgical scar (Figure 1). There was no evidence of inguinal lymphadenopathy. A broad cutaneous shave biopsy was performed which demonstrated a dermal proliferation of signet ring cells with abundant mucin and epithelial extension (Figures 2 and 3). Tumor cells were immunoreactive with CDX-2 (Figure 4), AE1/AE3, CK20 (Figure 5), carcinoem-bryonic antigen (CEA), and epithelial membrane antigen (EMA) stains; tumor cells were negative for CK7, CK5/6, P63, GCDFP-15, and S-100. Colloidal iron stain highlighted intracellular mucin deposition. The histologic features and immunohistochemical profile in this case were compatible with cutaneous metastasis of SRCAA. CEA levels were elevated at 4.7 ng/ml. CT and PET scan remained negative for any intra-abdominal involvement. The patient is currently following with oncology.

DISCUSSION

Signet ring cell carcinomas, frequent in the stomach and intestine, are adenocarcinomas with mucus-producing tumor cells. SRCAA is rare, comprising only 4 % of all primary appendiceal neoplasms.¹ SRCAA is a clinically aggressive type of cancer that often spreads to the pelvic lymph nodes, ovaries, and peritoneal surfaces by the time of diagnosis.^1-6 The most common presentation is right lower quadrant abdominal pain mimicking acute appendicitis.^7,8 Advanced abdomino-pelvic malignancies can also present as a metastatic umbilical nodule, termed a sister Mary Joseph nodule. There have been cases of reported inheritance of signet ring cell carcinomas caused by mutation of CDH1 gene, which encodes E-cadherin, an important glycoprotein in cell-cell adhesion.^9,10 Somatic mutations of APC gene have also been reported in gastric signet ring cell carcinoma.¹¹

Diagnosis is confirmed with cutaneous biopsy and imaging studies. Histologically, the appearance of signet ring cells result from formation of large vacuoles of mucin that displace the nucleus to the cell’s periphery.¹² Primary cutaneous signet ring cell carcinoma (PCSRCC) is a rare entity of suspected sweat gland origin, which stain positively with MNF116, CA15-3, BCA225, GCDFP15, CEA, CA125, and CK20.^13-15,16 Given the rarity of PCSRCC, it is important to rule out metastatic primary visceral malignancy.

SRCAA is a histopathologically distinct tumor.^4,17 Reported cases describe tumor cells demonstrating diffuse, strong immunoreactivity against CK20, CDX-2, MUC-2, CEA, and focal immunopositivity for MUC-5AC.^3,18 CDX-2 is a useful marker to confirm an appendiceal origin; it can be used in conjunction with CK20, MUC-2, and MUC-5AC for confirmation.¹⁹ Imaging studies, such as CT scan, are helpful to identify, but not distinguish SRCAA from other histological types of appendiceal carcinomas. On imaging, spread to adjacent organs is evident in 76 % of SRCAA at presentation compared with the mucinous (63 %) and colonic type (37 %) carcinomas.²⁰

The treatment options for metastatic disease include systemic chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, cytoreductive surgery with a peritonectomy, and or a combination of the above treatments. It is controversial whether debulking surgery and intraperitoneal chemotherapy are worthwhile for all aggressive, advanced disease cases.³

The prognosis is considered very poor, with a 5 years survival rate of 18 %, this is the lowest overall 5 years survival rate of all the subtypes of appendiceal carcinoma.²¹ Those who presented with distant metastatic disease had an even lower 5 years survival rate of 7 %.²¹

CONCLUSION

Cutaneous metastasis of SRCAA is rare and may present as the only herald of disease recurrence. Noting the distinction between primary and metastatic sing ring cell carinomas is of high importance, as the evaluation, management, and prognosis for the two entities are distinct. Given these implications, the dermatologist plays an integral role and should be attentive to these diagnostic possibilities.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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