Chen, Tiffany Y

Musiek, Amy

Raval, Neel

Rosman, Ilana S

Shmuylovich, Leonid

Strickley, John

English

Digital Commons@Becker

Washington University School of Medicine Digital Commons@Becker 2020-Current year OA Pubs Open Access Publications 4-1-2021 Signet-ring cutaneous metastasis presenting with massive anasarca Neel Raval Washington University School of Medicine in St. Louis Leonid Shmuylovich Washington University School of Medicine in St. Louis John Strickley Washington University School of Medicine in St. Louis Tiffany Y Chen Albany Medical Center Ilana S Rosman Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/oa_4 Recommended Citation Raval, Neel; Shmuylovich, Leonid; Strickley, John; Chen, Tiffany Y; Rosman, Ilana S; and Musiek, Amy, "Signet-ring cutaneous metastasis presenting with massive anasarca." JAAD Case Reports. 10, 123 - 125. (2021). https://digitalcommons.wustl.edu/oa_4/399 This Open Access Publication is brought to you for free and open access by the Open Access Publications at Digital Commons@Becker. It has been accepted for inclusion in 2020-Current year OA Pubs by an authorized administrator of Digital Commons@Becker. For more information, please contact vanam@wustl.edu. Authors Neel Raval, Leonid Shmuylovich, John Strickley, Tiffany Y Chen, Ilana S Rosman, and Amy Musiek This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/oa_4/399 CASE REPORTSignet-ring cutaneous metastasis presentingwith massive anasarcaNeel Raval, BS,a Leonid Shmuylovich, MD, PhD,a John Strickley, MD,a Tiffany Y. Chen, MD,cIlana S. Rosman, MD,a,b and Amy Musiek, MDaSt. Louis, Missouri and Albany, New YorkKey words: anasarca; case report; dermatology; edema; Hoffman’s syndrome; metastasis; signet-ring cellcarcinoma.INTRODUCTIONSignet-ring cell carcinomas (SRCC) are poorly-differentiated neoplasms that generally arise fromgastrointestinal or breast tissue and are associatedwith poor prognosis.1 Malignant signet-ring cellscontain abundant cytoplasmic mucin and a periph-erally displaced nucleus. Of note, these neoplasmshave an unusual tendency to infiltrate surroundingtissues, which is thought to be due to the loss of E-cadherin.2 This is clearly illustrated by the gastricSRCC variant, known as ‘‘linitis plastica,’’ which canresult in the thickening of the stomach wall.3Similarly, SRCC can metastasize to the peritoneum,leading to omental caking, a classic radiologicpattern describing the infiltration of omental fat bysoft-tissue material (eg, Krukenberg tumors).Dermatologists seldom identify SRCC in practice,most probably due to a combination of their sporadicprevalence and wide-ranging cutaneous manifesta-tions. Here, we report a remarkable case of SRCCpresenting with massive anasarca diagnosed solelyvia skin biopsy.CASE REPORTA 63-year-old woman with a history of basal cellcarcinoma, hypothyroidism, and tobacco use pre-sented to the emergency department from hernursing home complaining of bilateral lower ex-tremity edema coupled with a rapid decline inoverall health. Edema of the lower extremitiesinexplicably began about 5 months prior to admis-sion. During the interim, she experienced gradualweight loss from her face and upper body, diffusedhair loss from the scalp, and significant orthopnea,ultimately requiring her transfer to a skilled nursingfacility. While there, she suffered a pulmonary em-bolism and had several inconclusive workups for hergross deterioration. Aggressive diuresis failed toprovide any significant relief from edema, whichprompted her hospital admission.On physical examination (Fig 1, A and B), she hada massive indurated edema of the lower bodyextending to the inframammary area, which stoodin stark contrast to the cachectic appearance of theupper extremities, chest, head, and neck. The lowerextremity skin was thickened and leathery, with veryfaint overlying scattered erythema on the pretibialareas alone. No frank nodularity, papules, ulcera-tions, or violaceous lesions were found.Initial diagnostic workup revealed hemoglobin of7.9 g/dL, elevated erythrocyte sedimentation rate(89 mm/hr), and elevated thyroid-stimulating hor-mone (18.6 mIU/mL) with depressed free T4(0.72 ng/dL). A computed tomography scan showedevidence of diffuse body wall edema and skinthickening with hypertrophy and calcification ofthe proximal lower extremity musculature. Thesechanges were uniformly distributed, althoughslightly worse in dependent areas (sacrum andproximal thighs). When taken together with hypo-thyroidism, these imaging findings suggested aAbbreviation used:SRCC: Signet-ring cell carcinomaFrom the Division of Dermatologya and Department of Pathology& Immunology, Washington University School of Medicine, St.Louis,b and Department of Pathology, Albany Medical Center.cFunding sources: None.IRB approval status: Not applicable.Correspondence to: Amy Musiek, MD, Division of Dermatology,Washington University School of Medicine, 4590 Children’sPlace, Campus Box 8123, St. Louis, MO 63110. E-mail: amusiek@wustl.edu.JAAD Case Reports 2021;10:123-5.2352-5126 2021 by the American Academy of Dermatology, Inc. Publishedby Elsevier, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).https://doi.org/10.1016/j.jdcr.2021.02.009123diagnosis of Hoffman’s syndrome, a rare form ofhypothyroid myopathy presenting with muscularpseudohypertrophy. Nevertheless, clinical uncer-tainty necessitated further evaluation.The dermatology department was consulted and askin biopsy was performed from the most superiorregion of the anterior abdominal wall. This locationwas chosen as it was typical of the edematouschanges seen throughout, as well as to avoid thestatic changes that can occur after lower leg biopsies.On histopathologic examination (Fig 2, A and B),there was tremendous edema with scattered cellshaving a signet-ring morphology within the deepreticular dermis and subcutis. Lesional cells stainedpositive with pancytokeratin, CK7, SATB2, andCDX-2, which was suggestive of a non-cutaneousprimary malignancy. GATA3, CK20, and neuroendo-crine markers, synaptophysin and chromogranin,were negative. Colloidal iron highlighted mucinwithin atypical cells and no lymphovascular invasionwas observed. Collectively, the histopathologic andimmunophenotypic findings pointed to a metastaticSRCC of gastrointestinal origin.Subsequently, the patient underwent abdominalultrasonography, esophagogastroduodenoscopy,colonoscopy with biopsy, and fluorodeoxyglucose-positron emission tomography with computed to-mography. Tumor marker studies were notable forelevated CEA, CA 19-9, CA 15-3, and CA 125 antigen.Imaging studies, as well as tissue biopsies of colonicand esophageal mucosa, failed to identify a primarySRCC.The patient was transferred to the medicaloncology department for further management, witha diagnosis of metastatic adenocarcinoma due to thepresence of signet-ring cells. She tolerated inpatientfolinic acid, 5-fluorouracil, and oxaliplatin therapyand was referred to a skilled nursing facility withplans for outpatient follow-up. Regrettably, shesuccumbed to septic shock soon after dischargeand no autopsy was performed.DISCUSSIONWe present a remarkable case where a patientwith immense edema of the abdomen and lowerextremities was diagnosed with metastatic visceraladenocarcinoma (SRCC) solely via skin biopsy.Physicians must consider several pathophysio-logic mechanisms when evaluating skin thickeningand lower extremity edema. Iatrogenic culpritsinclude medications (ie, dihydropyridine calciumchannel blockers) or surgical lymph node dissec-tions. Infectious etiologies (eg, lymphatic filariasis)should be ruled out in those with pertinent travelhistories. Infiltrative processes, such as amyloidosis,myxedema, or sarcoidosis, present unique chal-lenges when they are not accompanied by classicsymptoms (weight gain/loss, fatigue) or other typicalfeatures (hair/nail changes, uveitis). These featurescan prolong arriving at the correct diagnosis, whichis worrisome for both patient and physician. Ourcase determined that SRCC is the infiltrative processresponsible for anasarca, which has not yet beenreported.In prior literature, cutaneousmetastases fromSRCCare described as papulonodular, sclerodermoid, orinflammatory-appearing lesions.4 Illustrative exam-ples of these reactionary patterns include carcinomaen cuirasse and carcinoma erysipeloides, often in thesetting of metastatic gastric or breast SRCC.4,5 TheseFig 1. Clinical presentation. A, Indurated edema of bilateral lower extremities. B, Edemaextending to the inframammary area with cachexia of upper extremities and thorax.JAAD CASE REPORTSAPRIL 2021124 Raval et aldistinct morphologies can provide strong clues for thedermatologist but are scarcely observed in commonpractice. Furthermore, SRCC can mimic benign pro-cesses, such as allergic contact dermatitis,6 or appearas localized, asymptomatic scarring.7 In addition toobtaining a comprehensive history and performing afull body skin examination, these reports on cuta-neous manifestations of SRCC emphasize that theclinician must harbor a high index of suspicion and alow threshold for accepting skin biopsy results toavoid delays in diagnosis and treatment.After a biopsy, gross histopathologic evaluationand targeted immunostaining are essential and willoften help in identifying the primary cancer. Painteret al provided a concise review of relevant immuno-histochemical markers that dermatologists mayencounter.8 In our case, the presence of signet-ringcells prompted immunostaining for common gastro-intestinal malignancies with CK-7/CK-20, SATB2,and CDX-2, in addition to GATA3 for breast andbladder primaries.6 Negative synaptophysin andchromogranin militated against a neuroendocrineetiology.To summarize, dermatologists should consider adiagnosis of SRCC when faced with a confusingclinical picture that could be explained by aninfiltrative process. Moreover, this case underscoresthe powerful diagnostic utility of a skin biopsy,which provided the only evidence for an internalmalignancy in this case.Conflicts of interestDr Musiek reports the following: Kyowa - advisoryboard; Helsinn - advisory board; Elorac, Sologenix,miRagen, Connect, Pfizer, and Menlo - investigator.Author Raval and Drs Shmuylovich, Strickley, Chen, andRosman have no conflicts of interest to report.REFERENCES1. Chu PG, Weiss LM. Immunohistochemical characterization ofsignet-ring cell carcinomas of the stomach, breast, and colon.Am J Clin Pathol. 2004;121(6):884-892.2. Chan JK, Wong CS. Loss of E-cadherin is the fundamental defectin diffuse-type gastric carcinoma and infiltrating lobular carci-noma of the breast. Adv Anat Pathol. 2001;8(3):165-172.3. Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J.Signet-ring cell carcinoma of the stomach: Impact on prognosisand specific therapeutic challenge. World J Gastroenterol. 2015;21(40):11428-11438.4. Kaur S, Aggarwal P, Dayal S, Sangwan A, Jain VK, Jindal N.Cutaneous metastasis from signet-ring gastric adenocarcinomain a carcinoma en cuirasse pattern: an unusual clinical-diagnosticsequence. Indian J Dermatol. 2015;60(6):637.5. Oliveira GM, Zachetti DB, Barros HR, Tiengo A, Romiti N. Breastcarcinoma en Cuirasseecase report. An Bras Dermatol. 2013;88(4):608-610.6. Ahn SJ, Oh SH, Chang SE, et al. Cutaneous metastasis ofgastric signet ring cell carcinoma masquerading as allergiccontact dermatitis. J Eur Acad Dermatol Venereol. 2007;21(1):123-124.7. Aneiros-Fernandez J, Husein-ElAhmed H, Arias-Santiago S, et al.Cutaneous metastasis as first clinical manifestation of signetring cell gastric carcinoma. Dermatol Online J. 2010;16(3):9.8. Painter JT, Clayton NP, Herbert RA. Useful immunohistochem-ical markers of tumor differentiation. Toxicol Pathol. 2010;38(1):131-141.Fig 2. Histopathology. A, Signet-ring cells. (Hematoxylin-eosin stain; original magnification:3200.) B, Tissue stained with CK-7 (colorectal). (Original magnification: 3100.)JAAD CASE REPORTSVOLUME 10Raval et al 125

Signet-ring cutaneous metastasis presenting with massive anasarca

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Signet-ring cutaneous metastasis presenting with massive anasarca

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