What Is This Skin Lesion?

A 66-year-old African American man with a history of multiple comorbidities was referred for evaluation of an umbilical mass (Figure 1) that was present for several months. He noticed the lesion at approximately the same time that he started experiencing abdominal pain. He reported serous drainage when picking at the lesion and experienced tenderness on palpation. Additionally, he endured night sweats, occasional chills, a 20-lb weight loss, and anorexia. Otherwise, he denied constipation, melena, hematochezia, nausea, vomiting, and diarrhea. His family history was noncontributory.

What Is Your Diagnosis?

Diagnosis: Sister Mary Joseph Nodule

Figure 1. Periumbilical area with two slightly hyperpigmented and indurated nodules and a verrucous, excoriated protrusion in the center of the umbilicus.

First described in 1854 by Baluff ¹ and again in 1864 by Storer,² the eponymous Sister Mary Joseph nodule (SMJN) was documented in the literature before it received its official title. The nodule was eventually named after Dr William J. Mayo’s surgical assistant, Julia Dempsey, who worked with him at St. Mary’s Hospital in Minnesota from 1890 to 1915.^1,3 She was the first to establish the rare correlation between umbilical nodules and diffuse intraperitoneal malignancies. Dr Mayo presented this association in 1928 as the “pant button umbilicus.”¹ However, in 1949, British surgeon Hamilton Bailey renamed the nodule SMJN in his book Physical Signs in Clinical Surgery.^1,3 

SMJN is often confused with other acquired and congenital pathologies. However, once diagnosed, it indicates a diffuse, metastatic disease process that is often inoperable. It can be an early sign, a sign of progression, and/or a sign of recurrence.⁴ SMJN, though a poor prognosticator, can help focus a sometimes nonspecific presentation.

Epidemiology

SMJN has most commonly been described in the adult population, but it has also been reported in children.^5-7 It is a rare finding, occurring in 1% to 3% of adult patients with abdominopelvic malignancy. Of all SMJN cases, 30% represent metastatic tumor deposition from a primary malignancy in another location.⁸ The gastrointestinal (GI) tract is the most common location for the primary tumor (35%-65%). GI sources include the stomach (25%), colon/rectum (10%), and pancreas (7%). SMJNs can also originate from gynecological tumors (12%-35%). Other locations have been reported, including gallbladder, liver, lung, prostate, breast, fallopian tube, peritoneum, endometrium, bladder, kidney, vagina, and penis (3%-6%).⁸ Of note, SMJN with a GI source occurs more commonly in men, whereas in women SMJN more often develops from a gynecological source (particularly ovarian cancer).⁹

Clinical Presentation

SMJNs usually present as white, purple, or dark red irregular and indurated papules or nodules (Figure 1). They usually measure 0.5 cm to 2 cm in diameter, but cases of up to 10 cm in diameter have been reported.⁸ Ulceration and necrosis at the site can cause pain, discomfort, and pruritus.¹⁰ Secretion of mucinous, purulent, or bloody discharge is not uncommon.¹¹ Although SMJNs can occur alone, they often present with other signs, such as ascites, pleural effusion, and constitutional symptoms associated with the underlying malignancy. The constitutional symptoms include fever, chills, night sweats, anorexia, weight loss, and fatigue.  

Pathogenesis 

The cause of SMJNs is poorly understood. Possible mechanisms for pathogenesis include peritoneal extension of the primary malignancy (thought to be most common), hematogenous/ lymphatic extension, and extension via ligaments of embryonic origin.^4,10,12,13 In very rare instances, iatrogenic seeding of malignant cells during laparoscopy can give rise to a SMJN.¹⁴ 

Differential Diagnosis

The differential diagnosis for an umbilical mass can include nonneoplastic and neoplastic causes. 

The nonneoplastic causes are summarized in Table 1^10,13,15 and can generally be ruled out by thorough history and examination.^10,12 It is important to procure a clear surgical history looking for any abdominal procedures that could lead to umbilical hernia as they may present similarly to a SMJN if the overlying skin is irritated. For female patients, a thorough menstrual history can reveal umbilical symptoms occurring cyclically, which may represent an endometrial implant. Once nonneoplastic causes are ruled out, the next step is to explore neoplastic possibilities.

Neoplastic causes are categorized as benign or malignant; malignant causes are further divided into primary causes, which include primary umbilical malignancy (melanoma, basal cell carcinoma, squamous cell carcinoma, myosarcoma, primary umbilical adenocarcinoma), or metastatic causes, which include metastatic umbilical malignancy.^10,12 Other etiologies of umbilical masses are summarized in Table

2^10,13,15. The malignant causes are differentiated based on histological appearance and immunohistochemical (IHC) staining, which are further discussed below.

Although various causes exist for umbilical masses, a misdiagnosis can lead to poor outcomes, thus necessitating a high index of suspicion for the more sinister causes.

Pathology

Suspicion for a SMJN begins with a thorough history and physical examination. Further work-up with laboratory studies and imaging modalities such as computed tomography (CT) or positron emission tomography (PET) scans can be helpful in determining other possibilities, but definitive diagnosis is made with biopsy and IHC stain.⁸

If metastatic adenocarcinoma at the umbilicus is present, histopathology will show fibromuscular tissue infiltrated by malignant-appearing glandular structures with associated desmoplastic response.¹⁵ 

IHC staining can be used to confirm the presence of metastatic adenocarcinoma. In the case of adenocarcinoma of intestinal origin, a positive cytokeratin (CK) 20, caudal type homeobox 2 (CDX2), and positive special AT-rich sequence-binding protein 2 (SATB2) with a negative CK7 are often characteristic.¹⁵ Various combinations of the above stains and additional IHC stains that can be used to differentiate the origin of a SMJN are listed in Table 3.

Treatment and Prognosis 

The mean life expectancy for patients with a SMJN is 2 to 11 months without treatment.¹¹ Depending on the primary organ system affected and the extent of metastasis, a decision can be made to either pursue an aggressive management option or a palliative approach.¹¹ Aggressive measures include a combination of surgery, radiotherapy, and chemotherapy that may be capable of prolonging a patient’s life, with a mean survival of 17.6 to 21 months.^11,13 

Our Patient

Biopsy of the umbilical lesion demonstrated metastatic adenocarcinoma (Figures 2 and 3). IHC stains were positive for CK20, CDX-2, and SATB-2 but negative for CK7; these results, collectively, support the diagnosis of metastatic carcinoma of intestinal origin.

Figure 2. Biopsy of the umbilical nodule showing a moderately differentiated metastatic adenocarcinoma. Hematoxylin-eosin staining, x40.

CT and PET scans were performed and showed a jejunal mass, diffuse liver metastases, and a cutaneous metastasis localized to the umbilicus. After the diagnosis, our patient was started on palliative chemotherapy to which he is responding well and is being followed up closely.

Figure 3. Higher magnification showing atypical columnar cells forming glandular structures. Hematoxylin-eosin staining, x100.

Conclusion

SMJN is a well-documented sign of an underlying visceral neoplasm that should be considered in the presence of an umbilical lesion. It is important for dermatologists to be familiar with SMJN, because it is not uncommonly the only presenting sign of an occult malignancy.

Dr Paka is an internal medicine intern at Mount Sinai St. Luke’s & Mount Sinai West in New York, NY. Dr Alapati is chief of dermatology and a dermatopathologist at Brooklyn Veterans Hospital in Brooklyn, NY. Dr Kazlouskaya is a dermatologist and dermatopathology fellow at SUNY Downstate Medical Center,  Department of Dermatology, in Brooklyn, NY. Dr Lai is a dermatology resident at SUNY Downstate Medical Center, Department of Dermatology, in Brooklyn, NY. 

Disclosure: The authors report no relevant financial relationships.  

References

1. Trebing D, Göring HD. The umbilical metastasis. Sister Mary Joseph and her time [in German]. Hautarzt. 2004;55(2):186-189. doi:10.1007/s00105-003-0675-2

2.  Storer H. Circumscribed tumour of the umbilicus closely simulating umbilical hernia. Boston Med Surg J. 1864;19:73.

3. Powell JL. Powell’s pearls: eponyms in medical and surgical history. Sister Joseph’s Nodule; Sister Mary Joseph (1856-1939). J Surg Educ. 2011;68(5):442-443. doi:10.1016/j.jsurg.2011.02.009

4. Gibson JAG, Thompson WR, Konamme S, Bhattacharya S. Sister Mary Joseph nodule: a diagnostic challenge. BMJ Case Rep. 2018;2018. doi:10.1136./bcr-2017-223674

5. Albano EA, Kanter J. Images in clinical medicine. Sister Mary Joseph’s nodule. N Engl J Med. 2005;352(18):1913. doi:10.1056/NEJMicm040708

6. Doros L, Kaste SC, Rodriguez-Galindo C. Sister Mary Joseph’s nodule as presenting sign of a desmoplastic small round cell tumor. Pediatr Blood Cancer. 2008;50(2):388-390. doi:10.1002/pbc.20915

7. Norman JT, Wagner ML, Chintagumpala M. Umbilical metastasis (Sister Mary Joseph’s nodule) in a child. Pediatr Radiol. 1998;28(1):56-58. doi:10.1007/s002470050293

8. Touré PS, Tall CT, Dioussé P, et al. Sister Mary Joseph nodule revealing digestive and ovarian carcinoma: report of 4 cases [in French]. Pan Afr Med J. 2015;22:269. doi:10.11604/pamj.2015.22.269.8022

9. Wronski M, Klucinski A, Krasnodebski IW. Sister Mary Joseph nodule: a tip of an iceberg. J Ultrasound Med. 2014;33(3):531-534. doi: 10.7863/ultra.33.3.531

10. Geller SA, de Campos FPF. Sister Mary Joseph nodule: it does not bode well. Autops Case Rep. 2014;4(3):5-7. doi:10.4322/acr.2014.022

11. Palaniappan M, Jose WM, Mehta A, Kumar K, Pavithran K. Umbilical metastasis: a case series of four Sister Joseph nodules from four different visceral malignancies. Curr Oncol. 2010;17(6):78-81.

12. DeBardeleben J, Cohen M, Rodgers SK. Peritoneal carcinomatosis presenting as a Sister Mary Joseph nodule. Ultrasound Q. 2017;33(4):300-302. doi:10.1097/RUQ.0000000000000314

13. Gaiser MR, Schäkel K, Helmbold P. Lest we forget: Sister Mary Joseph and her nodule. Int J Dermatol. 2013;52(5):587-588. doi:10.1111/j.1365-4632.2012.05787.x.

14. Talebi S, Chaudhari S. Sister Mary Joseph nodule. QJM. 2016;109(6):419-420. doi:10.1093/qjmed/hcv222

15. Ko CJ, Cassarino D. Metastatic tumors to skin. ExpertPath. https://app.expertpath.com/document/metastatic-tumors-to-skin/16a2f39e-ba9a-46aa-902e-731b8f0e2d3c?searchTerm=sister%20mary%20joseph. Accessed October 4, 2019.