histopathological features of subcutaneous sarcoidosis

CME ARTICLE

Histopathological Features of Subcutaneous Sarcoidosis

Joaquim Marcoval, MD,* Rosa M. Penín, MD,† and Juan Mañá, MD‡

Abstract: Only a few series of patients with systemic sarcoidosisand specific subcutaneous lesions have been reported. We reviewedour patients with systemic sarcoidosis with specific subcutaneouslesions to analyze their histopathological features and their relation-ship with clinical features of the systemic disease. Patients withsystemic sarcoidosis with predominantly subcutaneous sarcoidgranulomas diagnosed between 1980 and 2016 in Bellvitge Univer-sity Hospital were enrolled. We also analyzed patients with clinicallyand histopathologically identical lesions in whom a diagnosis ofsystemic sarcoidosis could not be made during follow-up. Twenty-eight patients with systemic sarcoidosis presented specific sub-cutaneous lesions (23 women and 5 men, mean age 55.64 SD 12.26years). Dermal involvement was observed in 10 cases, alwaysdiscrete and limited to deep reticular dermis. The distribution of thegranulomatous infiltrate was lobular in 7 cases and lobular and septalin 21. Fibrosis was observed in 21 cases. There were no significantdifferences in persistence of lesions or persistence of systemicdisease activity when comparing patients with and without fibrosis.In conclusion, fibrosis is a frequent finding in subcutaneoussarcoidosis, and although it may be intense, it is not associated withpulmonary fibrosis or with .2 years of persistence of systemicsarcoidosis activity.

Key Words: histopathology, sarcoidosis, skin, subcutaneous sar-coidosis

(Am J Dermatopathol 2020;42:233–243)

LEARNING OBJECTIVESAfter completing this CME activity, physicians should

be better able to:

1. Identify the histopathological features of subcutaneoussarcoidosis.

2. Assess the presence of fibrosis in subcutaneous sarcoidosisand its relationship with the clinical features of systemicsarcoidosis.

INTRODUCTIONSarcoidosis is a multisystem disease defined by the

formation of noncaseating granulomas in various organs,mainly the lungs, lymph nodes, eyes, and skin.1 Subcutane-ous lesions are occasionally observed in sarcoidosis. Themost frequent subcutaneous lesion in sarcoidosis is erythemanodosum, a nonspecific lesion usually associated with acuteforms of the disease, in particular Löfgren syndrome. How-ever, patients with systemic sarcoidosis may also developgranulomatous infiltration of the subcutaneous tissue as a spe-cific cutaneous lesion.2 Only a few short series of patientswith systemic sarcoidosis and subcutaneous specific lesionshave been reported to date,3–6 one of which included the first10 patients of the present series.6 The largest previous studyreported only 16 patients.4 Probably because of their lowincidence, the histopathological features of the lesions andtheir relationship with clinical features of the systemic diseaseare not well established. Some studies suggest that subcuta-neous sarcoidosis usually occurs in acute forms of sarcoido-sis, but others do not confirm this fact.5

Our objective was to review our series of patients withsystemic sarcoidosis with subcutaneous sarcoidosis lesions toanalyze the histopathological features of the subcutaneouslesions and their possible relationship with clinical features ofthe systemic disease. We also analyzed those patients withclinically and histopathologically indistinguishable lesions inwhom a diagnosis of systemic sarcoidosis could not be madeduring follow-up.

MATERIALS AND METHODSAll patients with systemic sarcoidosis and specific

subcutaneous lesions diagnosed between 1980 and 2016 atBellvitge University Hospital (an 800-bed university referralcentre in Barcelona, Spain) were enrolled. The diagnosis ofsystemic sarcoidosis was made based on the classic criteria1:a compatible clinical and radiological picture; histologicaldemonstration of noncaseous granulomas in one or more tis-sues, with stains and cultures negative for mycobacteria andfungi; and exclusion of other granulomatous diseases. Sub-cutaneous sarcoidosis was defined as subcutaneous lesionswith inflammatory infiltrates composed of sarcoid granulomaslocated predominantly in the hypodermis.

The patients were followed clinically in the sarcoidosisclinic of Bellvitge University Hospital. Patients’ clinicalcharts were reviewed to collect the following data: age, sex,date of diagnosis, location of lesions, association with ery-thema nodosum, radiological stage at diagnosis of skin le-sions, serum angiotensin-converting enzyme levels, durationof subcutaneous lesions, duration of systemic sarcoidosisactivity, and need for systemic corticosteroid treatment.

From the *Dermatologist, Department of Dermatology, Hospital Universitaride Bellvitge, Universitat de Barcelona, Barcelona, Spain; †Pathologist,Department of Pathology, Hospital Universitari de Bellvitge, Universitatde Barcelona, Barcelona, Spain; and ‡Clinical Chief, Department of Inter-nal Medecine, Hospital Universitari de Bellvitge, Universitat de Barcelona,Barcelona, Spain.

All authors, faculty, and staff in a position to control the content of this CMEactivity and their spouses/life partners (if any) have disclosed that theyhave no financial relationships with, or financial interests in, anycommercial organizations relevant to this educational activity.

Correspondence: Joaquim Marcoval, MD, Dermatologist, Department ofDermatology, Hospital de Bellvitge, c/Feixa Llarga s/n, Hospitalet deLlobregat, Barcelona 08907, Spain (e-mail: [email protected]).

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Am J Dermatopathol � Volume 42, Number 4, April 2020 www.amjdermatopathology.com | 233

Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Histopathological specimens were reviewed to analyzethe location of the granulomatous infiltrate, presence of deepdermal involvement, distribution of the granulomatous infil-trate in the subcutaneous tissue (lobular vs. septal vs. mixed),presence and distribution of fibrosis, presence of giant cells(type and density), presence of necrosis, presence of foreignbodies, density of lymphocytic component, and presence ofother inflammatory cells.

Statistical AnalysisData were analyzed with SPSS (v17.0 for Windows;

SPSS, Inc, Chicago, IL). Categorical variables were com-pared using the x2 test or Fisher exact test. Continuous var-iables were compared using the Student t test when normalityof data distribution was confirmed. Otherwise, the Mann–Whitney U test was performed.

RESULTSTwenty-eight patients with systemic sarcoidosis and

specific subcutaneous lesions were diagnosed between 1980and 2016. There were 23 women and 5 men, with a mean age55.64 SD 12.26 years (range 29–84 years). All patients werewhite except for 2 women of North African descent. Allpatients presented nontender, indurated subcutaneous nodularlesions, covered by normal appearing skin, and in some casesonly detected by palpation (Fig. 1). The lesions were locatedpredominantly in the forearms in 20 patients (limited to theforearms in 13). Subcutaneous granulomatous lesionsinvolved more than 1 anatomical site in 9 cases. Six patientspresented a single lesion. Biopsy sites were the forearm (20cases), face (3), hand (2), lower extremity (2), and arm (1)(Table 1).

Subcutaneous sarcoidosis was present at diagnosis ofthe systemic disease in 26 of 28 cases (93%) (in 9 cases,subcutaneous sarcoidosis lesions appeared at 2–24 monthsprevious to the diagnosis of systemic sarcoidosis, and in 17,they appeared simultaneously with the diagnosis). Only 2patients developed subcutaneous sarcoidosis after diagnosis

of the systemic disease. Seven patients presented erythemanodosum shortly before the onset of subcutaneous sarcoidosislesions. Lesions of subcutaneous sarcoidosis persisted fora mean time of 15.33 SD 16.52 months (range 2–60 months).Radiological stage was 0 for 1 patient, I for 20, II for 6, III for1, and IV for 0. Serum angiotensin-converting enzyme levelswere high at diagnosis in 16/28 patients (57%). The activityof systemic sarcoidosis persisted for between 4 and 156months (mean 30.62 SD 36.66 months) and was .2 yearsin only 11/26 patients with more than 2 years of follow-up(42%). Only 11/28 patients (39.3%) received therapy withoral corticosteroids, most of them due to extracutaneous dis-ease. None of our patients developed chronic or serious com-plications of sarcoidosis such as pulmonary fibrosis.

HistopathologyAll patients showed a granulomatous infiltrate com-

posed of sarcoid granulomas (epithelioid cell granulomaswith sparse lymphocytic component). Epidermis was normalin all cases in which it could be evaluated (3 specimens didnot include epidermis). Dermal involvement was observed in10 cases, always discrete and limited to the deep reticulardermis (Fig. 2). The dermal–epidermal interface was involvedin 22/28 cases (78.6%). The distribution of the granulomatousinfiltrate was lobular in 7 cases (25%) and lobular and septalin 21 cases (75%) (Fig. 2).

Fibrosis was observed in 21/28 cases (75%). In most ofthese cases, fibrosis was septal and/or intergranulomatous(septal in 5 cases, intergranulomatous in 4, and septal andintergranulomatous in 3). In 3 cases, fibrosis was diffuse, andin the remaining 6 cases, it did not follow any definite pattern(Figs. 3 and 4). Fibrosis was intense in 8 cases (as prominentas the granulomatous infiltrate in 4 and predominating overthe granulomatous infiltrate in 4). Table 1 shows the compar-ison of cases with and without fibrosis.

Giant cells were observed in all specimens. Foreign-body type predominated in 18 specimens and Langhans typepredominated in 5, while in the other 5, both types of giantcell were equally observed. Giant cell density was quantified

FIGURE 1. A–D, Clinical images of typical cases ofsubcutaneous sarcoidosis. Nontender, indurated,fusiform subcutaneous lesions are observedmainly in the forearms.

Marcoval et al Am J Dermatopathol � Volume 42, Number 4, April 2020

234 | www.amjdermatopathology.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.


TABLE 1. Histopathology of Subcutaneous Sarcoidosis. Comparison of Cases With and Without Fibrosis

Cases With Fibrosis n = 21 Cases Without Fibrosis n = 7 P

Age (yr) n = 28 57.43 SD 11.42 50.29 SD 14.04 0.151

Sex 5M/23F 5M/16F 0M/7F 0.290

Biopsy site n = 28

Forearm 20 (71.4%) 17/21 (80.9%) 3/7 (42.9%)

Face 3 (10.7%) 2/21 (9.5%) 1/7 (14.3%)

Hand 2 (7.1%) 1/21 (4.8%) 1/7 (42.9%)

Lower limb 2 (7.1%) 0/21 (0%) 2/7 (28.6%)

Arm 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

.1 anatomical region 9/28 (32.1%) 6/21 (26.6%) 3/7 (42.9%) 0.646

Single lesion 6/28 (21.4%) 5/21 (23.8%) 1/7 (14.3%) 1.000

Erythema nodosum 7/28 (25%) 5/21 (23.8%) 2/7 (28.6%) 1.000

ECA elevated 16/28 (57.1%) 13/21 (61.9%) 3/7 (42.9%) 0.418

Rx stage n = 28

0 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

I 20 (71.4%) 13/21 (61.9%) 7/7 (100%)

II 6 (21.4%) 6/21 (26.6%) 0/7 (0%)

III 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

IV 0 0/21 (0%) 0/7 (0%)

Rx stage I vs. II–IV n = 27 0.137

I 20 (74.1%) 13/21 (61.9%) 7/7 (100%)

II–IV 7 (25.9%) 7/21 (33.3%) 0/7 (0%)

Systemic corticosteroids 11/28 (39.3%) 9/21 (42.9%) 2/7 (28.6%) 0.668

.2-year activity 11/26 (42.3%) 10/19 (52.6%) 1/7 (14.3%) 0.178

Persistence sc lesions (mo) 16.20 SD 15.20 12.86 SD 21.01 0.290

Systemic disease activity (mo) 32.74 SD 34.39 24.86 SD 44.69 0.082

Dermal granulomas 10/28 (35.7%) 7/21 (33.3%) 3/7 (42.9%) 0.674

Dermo–hypodermal interfaceinvolvement

22/28 (78.6%) 17/21 (80.9%) 5/7 (71.4%) 0.622

Subcutaneous pattern n = 28 0.043

Lobular 7 (25%) 3/21 (14.3%) 4/7 (57.1%)

Lobular + septal 21 (75%) 18/21 (85.7%) 3/7 (42.9%)

Granulomatous infiltrate n = 28

Confluent 11 (39.3%) 8/21 (38.1%) 3/7 (42.9%)

Nonconfluent 14 (50%) 11/21 (52.4%) 3/7 (42.9%)

Perivascular 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

Confl + nonconfl 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

Confl + perivasc 1 (3.6%) 0/21 (0%) 1/7 (42.9%)

Fibrinoid necrosis 8/28 (28.6%) 7/21 (33.3%) 1/7 (42.9%)

Foreign body 7/28 (25%) 4/21 (19%) 3/7 (42.9%) 0.318

Giant cell density n = 28

+ 15 (53.6%) 10/21 (47.6%) 5/7 (71.4%)

++ 12 (42.9%) 11/21 (52.4%) 1/7 (42.9%)

+++ 2 (7.1%) 1/21 (4.8%) 1/7 (42.9%)

Predominant giant cell type n = 28

Langhans 5 (17.9%) 4/21 (19%) 1/7 (42.9%)

Foreign body 18 (64.3%) 13/21 (61.9%) 5/7 (71.4%)

Both equal 5 (17.9%) 4/21 (19%) 1/7 (42.9%)

Inflammation n = 28

+ 14 (50%) 11/21 (52.4%) 3/7 (42.9%)

++ 13 (46.4%) 9/21 (42.9%) 4/7 (57.1%)

+++ 1 (3.6%) 1/21 (4.8%) 0/7 (0%)

Lymphocyte density n = 21

+ 14 (50%) 10/21 (47.6%) 4/7 (57.1%)

++ 14 (50%) 11/21 (52.4%) 3/7 (42.9%)

+++ 0 0/28 (0%) 0/7 (0%)

Bold indicates P is significant.

Subcutaneous SarcoidosisAm J Dermatopathol � Volume 42, Number 4, April 2020

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.amjdermatopathology.com | 235


as mild in 15 cases, moderate in 11, and intense in 2.Fibrinoid necrosis was observed in 8 cases (mild in 6,moderate in 1, and intense in 1). Foreign bodies weredetected in 7/28 patients (25%) (in 2 of them with micro-scopic appearance suggestive of silicone). Lymphocytedensity was quantified as mild in 14 cases, moderate in 14,and intense in none. Histiocytes were observed in 2 cases (thesame cases in which silicone was observed) and plasma cellsin only 1 case.

We investigated the possible relationships between theclinical and histopathological features analyzed. As expected,the presence of erythema nodosum was associated with ,2years of systemic disease activity (P = 0.010). Patients withfibrosis mainly presented a lobular and septal distribution ofthe granulomatous infiltrate, while in cases without fibrosis,the infiltrate was more frequently lobular (P = 0.043). Thepresence of a lobular pattern was associated with high giantcell density, mainly of foreign body-type (P = 0.028). All

specimens with foreign bodies showed foreign body-typegiant cells. Foreign bodies were not detected in specimensthat only showed Langhans-type giant cells. We did notdetect other relevant relationships.

Five patients with subcutaneous lesions that wereclinically and histopathologically indistinguishable from sub-cutaneous sarcoidosis did not fulfill criteria for systemicsarcoidosis during a follow-up of 24–144 months (mean64.80 SD 46.16). These were 5 female patients with a meanage of 62.40 SD 8.08 years. Table 2 shows the comparison ofthese 5 patients with the 28 patients suffering systemicsarcoidosis.

DISCUSSIONSubcutaneous sarcoidosis is in most reported series the

least frequent form of the classical specific cutaneous lesionsof systemic sarcoidosis. It has been reported to occur in

FIGURE 2. Low‐power view of subcutaneous sar-coidosis. Although in some cases, there may besparse granulomas the in deep dermis, theinflammatory infiltrate is usually sharply demar-cated in the dermo–hypodermic junction. Thegranulomatous infiltrate is usually mainly lobular(A) (H&E ·8), in some cases seems to pro-gressively involve the septa (B) (H&E ·8), and maybe massive (C and D) (H&E ·8).




1.4%–6% of patients with systemic sarcoidosis.3,7 In ourseries, subcutaneous sarcoidosis was diagnosed in 28 of 640patients with systemic sarcoidosis, representing 4.38%. Mostcases have been reported to occur in white women in the fifth

and sixth decades of life.8 The lesions are characteristicallylocated on the extremities, typically on the forearms, as fusi-form, hard, nontender subcutaneous nodular lesions withoutdermal or epidermal changes.4,6,9–12 This clinical presentation

FIGURE 3. Subcutaneous sarcoidosis with mainlylobular periseptal granulomatous infiltrate andprominent giant cells. A, H&E ·8; (B) H&E ·25;and (C) H&E ·40.

FIGURE 4. Massive granulomatous sub-cutaneous infiltrate composed of nakedsarcoid granulomas with prominent peri-granulomatous fibrosis. A, H&E ·8; (B) H&E·30; and (C) H&E ·100.




TABLE 2. Histopathology of Subcutaneous Sarcoidosis. Comparison of Patients With Specific Cutaneous Lesions of SystemicSarcoidosis and Those With Isolated Cutaneous Sarcoidosis (Subcutaneous Sarcoid Reaction)

SystemicSarcoidosis n = 28

Isolated SubcutaneousSarcoidosis n = 5 P

Age (yr) n = 33 55.64 SD 12.26 62.40 SD 8.08 0.227

Sex 5M/28F 5M/23F 0M/5F 0.569

Biopsy site n = 33

Forearm 25 20/28 (71.4%) 5/5 (100%)

Face 3 3/28 (10.7%) 0/5 (0%)

Hand 2 2/28 (7.1%) 0/5 (0%)

Lower limb 2 2/28 (7.1%) 0/5 (0%)

Arm 1 1/28 (3.6%) 0/5 (0%)

.1 anatomical region 12/33 9/28 (32.1%) 3/5 (60%) 0.328

Single lesion 7/33 6/28 (21.4%) 1/5 (20%) 1.000

Erythema nodosum 8/33 7/28 (25%) 1/5 (20%) 1.000

SACE elevated 18/33 16/28 (57.1%) 2/5 (40%) 0.639

Persistence sc lesions (mo) n = 33 15.33 SD 16.52 8.60 SD 6.91 0.548

Dermal granulomas 12/33 10/28 (35.7%) 2/5 (40%) 1.000

Dermo–hypodermal interfaceinvolvement

26/33 22/28 (78.6%) 4/5 (80%) 1.000

Subcutaneous pattern n = 33 1.000

Lobular 8 7/28 (25%) 1/5 (20%)

Lobular + septal 25 21/28 (75%) 4/5 (80%)

Granuloma type n = 33

Confluent 11 11/28 (39.3%) 0/5 (0%)

Nonconfluent 19 14/28 (50%) 5/5 (100%)

Perivascular 1 1/28 (3.6%) 0/5 (0%)

Confl + nonconfl 1 1/28 (3.6%) 0/5 (0%)

Confl + perivasc 1 1/28 (3.6%) 0/5 (0%)

Fibrosis 25/33 21/28 (75%) 4/5 1.000

Fibrosis type n = 25

Septal 7 5/28 (17.9%) 2/5 (40%)

Intergranulomatous 4 4/28 (14.3%) 0/5 (0%)

Septal + intergranulomatous 4 3/28 (10.7%) 1/5 (20%)

Diffuse 3 3/28 (10.7%) 0/5 (0%)

Without pattern 7 6/28 (21.4%) 1/5 (20%)

Fibrinoid necrosis 8/33 8/28 (28.6%) 0/5 (0%) 0.302

Foreign body 8/33 7/21 (25%) 1/5 (20%) 1.000

Giant cell density n = 33

+ 16 15/28 (53.6%) 1/5 (20%)

++ 14 11/28 (39.3%) 3/5 (60%)

+++ 3 2/28 (7.1%) 1/5 (20%)

Predominant giant cell type n = 33

Langhans 7 5/28 (17.9%) 2/5 (40%)

Foreign body 20 18/28 (64.3) 2/5 (40%)

Both equal 6 5/28 (17.9%) 1/5 (20%)

Inflammation n = 33

+ 15 14/28 (50%) 1/5 (20%)

++ 17 13/28 (46.4%) 4/5 (80%)

+++ 1 1/28 (3.6%) 0/5 (0%)

Lymphocyte density n = 33

+ 15 14/28 (50%) 1/5 (20%)

++ 16 14/28 (50%) 2/5 (40%)

+++ 2 0/28 (0%) 2/5 (40%)

Lymphocyte density + vs ++/+++ n = 33 0.346

+ 15 14/28 (50%) 1/5 (20%)

++/+++ 18 14/28 (50%) 4/5 (80%)

Bold indicates P is significant.SACE, serum angiotensin-converting enzyme.




is quite specific, so the diagnosis can be clinically suspected.Quite often these subcutaneous granulomatous lesions coexistwith or appear shortly after erythema nodosum (25% of casesin the present series). However, subcutaneous sarcoidosisnodules are nontender and flesh-colored, and more persistentthan erythema nodosum, so the 2 types of lesion are easilydistinguished clinically.3 In agreement with previous re-ports,4,8,9 in the present series, subcutaneous sarcoidosis usu-ally appeared at the onset of systemic sarcoidosis (26/28cases), was frequently the main complaint at diagnosis, andits biopsy was useful for the diagnosis of the systemic disease.

There are few reports or textbooks describing thehistopathological features of subcutaneous sarcoidosis.13

The diagnostic criteria were proposed by Vainsencher andWinkelmann3: identification of epithelioid or sarcoidal gran-ulomas with minimal lymphocytic inflammation predomi-nantly involving the panniculus. Some authors believe thatto fulfill this diagnosis, there should be no dermal involve-ment. In our experience, 10 of our 28 cases showed somegranulomas in the deep dermis, and so, we believe that min-imal dermal involvement can be accepted in the diagnosis ofsubcutaneous sarcoidosis. At low-power magnification, theinflammatory infiltrate composed of noncaseating granulomashas been reported to be predominantly lobular with minimalor no septal involvement, resembling a lobular panniculi-tis.3,14 In our series, the granulomatous infiltrate was exclu-sively lobular in 8 cases and in 25 cases also showed septalinvolvement. Granulomas were small, uniform in size, andmainly composed of epitheloid cells, with variable amountsof multinucleated giant cells, and a minor lymphocytic com-ponent. In all our cases, giant cells were observed, in some ofthem very prominently. Foreign body–type giant cells predo-minated over Langhans-type giant cells in most of our pa-tients. It is known that in some cases, small foci of necrosismay appear in the center of regressing sarcoid granulomas.15

In this line, fibrinoid necrosis was observed in 8 of our cases(mild in 6, moderate in 1, and intense in 1).

Polarizable foreign bodies have been observed in thedermis of 22%–50% of cutaneous sarcoidosis.16–20 In

subcutaneous sarcoidosis, foreign particles have also beenreported.6,17 In this study, foreign bodies were observed in7/28 cases (25%) (Fig. 5C), suggesting that, as with dermallesions, the presence of foreign bodies in subcutaneous gran-ulomatous lesions does not exclude a diagnosis of sarcoido-sis.18–20

The presence of fibrosis as a histopathologic feature ofsubcutaneous sarcoidosis has been highlighted in several casereports.13,21,22 This is not surprising since in organs such asthe lung, fibrosis can be extensive.13 However, it is not clearwhether fibrosis is universally present or an episodic find-ing,21 and whether the extent of fibrosis in subcutaneous sar-coidosis is related to the duration of the lesions or thepresence of fibrosis in other organs.13 In our series, fibrosiswas observed in 21 cases and was often intense (8 cases). Wedid not find a relationship with advanced radiological stage.Similarly, although in patients with fibrosis, subcutaneouslesions and systemic disease activity were slightly more per-sistent, these findings were not significant (Table 1).

Owing to the limited number of cases, it is difficult toassess the prognostic value of subcutaneous sarcoidosis in theevolution of the systemic disease. Some reports suggest that itis associated with acute forms of sarcoidosis.6 By contrast,a recent report of 9 cases suggests that subcutaneous sarcoid-osis is associated with chronic evolution of the systemic dis-ease.5 Our results are in concordance with the associationwith acute forms of systemic sarcoidosis, since in our series,subcutaneous sarcoidosis was predominantly associated withstage I chest radiograph and with ,2 years of persistence ofsystemic sarcoidosis activity (15/26, 58%).

There are several reports of patients with lesionsclinically and histopathology indistinguishable from specificsarcoidosis subcutaneous lesions which did not fulfill criteriafor systemic sarcoidosis. Ahmed and Harstad4 reported thata systemic disease component was not recognized in 4 of 20patients at the time subcutaneous sarcoidosis was diagnosed.We have observed 5 cases in which systemic sarcoidosiscould not be diagnosed in a mean follow-up time of 64.80months. Comparison with patients with systemic sarcoidosis

FIGURE 5. Intense perigranulomatous fibrosisalso showing some naked granulomas in the fatlobule (A) (H&E ·50) and (B) (H&E ·50). Intensediffuse fibrosis around granulomas with prom-inent giant cells (C) (H&E ·25) and (D) (H&E·50); a foreign body is observed at high magni-fication (D) (H&E ·50).




is shown in Table 2. It is worth noting that lymphocyte den-sity was higher in cases without systemic sarcoidosis,although the differences were not significant, probablybecause of the small number of cases. These patients cannotbe diagnosed with subcutaneous sarcoidosis, and they aremore usefully described as having isolated subcutaneous sar-coidosis or subcutaneous sarcoid reaction. However, thesepatients should be followed up to exclude a possible futureoutbreak of sarcoidosis.

Limitations of this study include the small number ofcases and the fact that it is a retrospective survey.

In summary, subcutaneous sarcoidosis usually appearsat the onset of systemic sarcoidosis and its biopsy can beuseful for the diagnosis of the disease. It has prognosissignificance since in patients with subcutaneous sarcoidosis,the activity of the systemic disease usually persists ,2 years.Histopathologically, the subcutaneous granulomatous infil-trate is predominantly lobular, but can also involve the septa(75% of cases). Minimal lower dermal involvement may beobserved in some patients. Fibrosis is a frequent finding insubcutaneous sarcoidosis, and although this may be intense, itis not associated with pulmonary fibrosis. Although the pres-ence of fibrosis in subcutaneous lesions is slightly more fre-quent in patients with .2 years of persistence of systemicsarcoidosis activity, the differences are not significant. Giantcells are frequently observed, predominantly of foreign body-type. As with dermal lesions of systemic sarcoidosis, thepresence of foreign bodies is not uncommon.

REFERENCES1. Hunninghake GW, Costabel U, Ando M, et al. ATS/ERS/WASOG state-

ment on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:149–173.

2. Mañá J, Marcoval J, Graells J, et al. Cutaneous involvement in sarcoid-osis: relationship to systemic disease. Arch Dermatol. 1997;133:882–888.

3. Vainsencher D, Winkelmann RK. Subcutaneous sarcoidosis. Arch Der-matol. 1984;120:1028–1031.

4. Ahmed I, Harstad S. Subcutaneous sarcoidosis: is it a specific subset ofcutaneous sarcoidosis frequently associated with systemic disease? J AmAcad Dermatol. 2006;54:55–60.

5. Ando M, Miyazaki E, Hatano Y, et al. Subcutaneous sarcoidosis: clinicalanalysis of nine patients. Clin Rheumatol. 2016;35:2277–2281.

6. Marcoval J, Maña J, Moreno A, et al. Subcutaneous sarcoidosis—clini-copathological study of 10 cases. Br J Dermatol. 2005;153:790–794.

7. Mayock RL, Bertrand P, Morrison CE, et al. Manifestations of sarcoid-osis: analysis of 145 patients, with a review of nine series selected fromthe literature. Am J Med. 1963;35:67–89.

8. Higgins EM, Salisbury JR, Du Vivier AW. Subcutaneous sarcoidosis.Clin Exp Dermatol. 1993;18:65–66.

9. Kalb RE, Epstein W, Grossman ME. Sarcoidosis with subcutaneousnodules. Am J Med. 1988;85:731–736.

10. Perez-Cejudo JA, Piqué E, Palacios SL, et al. Subcutaneous sarcoidosis,nodular lesions forming cords or bands. Actas Dermosifiliogr. 2006;97:223–224.

11. Yamada S, Yagi A, Shiraishi S, et al. A case of extensive subcutaneoussarcoidosis. J Dermatol. 1986;13:217–221.

12. Kuramoto Y, Shindo Y, Tagami H. Subcutaneous sarcoidosis with exten-sive caseation necrosis. J Cutan Pathol. 1988;15:188–190.

13. Resnik KS. The findings do not conform precisely: fibrosing sarcoidalexpressions of panniculitis as example. Am J Dermatopathol. 2004;26:156–161.

14. Requena L, Sánchez Yus E. Panniculitis. Part II: mostly lobular panni-culitis. J Am Acad Dermatol. 2001;45:325–361.

15. Barrier HJ, Bogoch A. The natural history of the sarcoid granuloma. AmJ Pathol. 1953;29:451–469.

16. Ball NJ, Kho GT, Martinka M. The histologic spectrum of cutaneoussarcoidosis: a study of twenty-eight cases. J Cutan Pathol. 2004;31:160–168.

17. Mangas C, Fernández-Figueras MT, Fité E, et al. Clinical spectrum andhistological analysis of 32 cases of specific cutaneous sarcoidosis. JCutan Pathol. 2006;33:772–777.

18. Marcoval J, Mañá J, Moreno A, et al. Foreign bodies in granulomatouscutaneous lesions of patients with systemic sarcoidosis. Arch Dermatol.2001;137:427–430.

19. Kim YC, Triffet MK, Gibson LE. Foreign bodies in sarcoidosis. Am JDermatopathol. 2000;22:408–412.

20. Callen JP. The presence of foreign bodies does not exclude the diagnosisof sarcoidosis. Arch Dermatol. 2001;137:485–486.

21. Resnik KS. Subcutaneous sarcoidosis histopathologically manifested asfibrosing granulomatous panniculitis. J Am Acad Dermatol. 2006;55:918–919.

22. Llamas-Velasco M, Godoy A, Fraga J, et al. Fibrosing cutaneous sar-coidosis. Actas Dermosifiliogr. 2012;103:331–333.




CME EXAMINSTRUCTIONS FOR OBTAINING AMA PRA CATEGORY 1 CREDITSTM

The American Journal of Dermatopathology includes CME-certified content that is designed to meet the educational needs of its readers.An annual total of 12 AMA PRA Category 1 Credits™ is available through the twelve 2020 issues of The American Journal of

Dermatopathology. This activity is available for credit through March 31, 2022.

Accreditation Statement

Lippincott Continuing Medical Education Institute, Inc, is accredited by the Accreditation Council for Continuing Medical Education toprovide continuing medical education for physicians.

Credit Designation Statement

Lippincott Continuing Medical Education Institute, Inc, designates this journal-based CME activity for a maximum of one (1) AMA PRACategory 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

To earn CME credit, you must read the article in The American Journal of Dermatopathology and complete the quiz, answering at least 80percent of the questions correctly. Mail the Answer Sheet along with a check or money order for the $15 processing fee, to Lippincott CME Institute,Inc, Wolters Kluwer Health, Two Commerce Square, 2001 Market Street, 3rd Floor, Philadelphia, PA 19103. Only the first entry will be consideredfor credit and must be postmarked by the expiration date. Answer sheets will be graded, and certificates will be mailed to each participant within 6 to8 weeks of participation. Visit http://cme.lww.com for immediate results, other CME activities, and your personalized CME planner tool.

CME EXAMINATIONApril 2020

Please mark your answers on the ANSWER SHEET.

After participating in this activity, the physician should be better able to: 1. Identify the histopathological features of subcutaneoussarcoidosis. 2. Assess the presence of fibrosis in subcutaneous sarcoidosis and its relationship with the clinical features of systemic sarcoidosis.

CME QUESTIONS

1. The most frequent location of subcutaneous sarcoidosis lesions is:a. Faceb. Scalpc. Forearmsd. Legse. Trunk

2. Regarding subcutaneous sarcoidosis, please select the wrong statement:a. Is most frequent in femalesb. Is clinically indistinguishable from erythema nodosum lesionsc. Is usually present at the onset of systemic sarcoidosisd. Its biopsy can be useful for the diagnosis of systemic sarcoidosis avoiding aggressive explorationse. Is more frequent in patients with radiological stage I

3. Regarding subcutaneous sarcoidosis, please select the wrong statement:a. Minimal dermal involvement can be acceptable for the diagnosis of subcutaneous sarcoidosisb. The granulomatous infiltrate is mainly lobularc. Foreign body type giant cells predominate over Langhans-type giant cells in most cases of subcutaneous sarcoidosisd. The presence of foreign bodies excludes the diagnosis of subcutaneous sarcoidosise. Fibrinoid necrosis can be observed in a third of cases

4. Regarding the presence of fibrosis in subcutaneous sarcoidosis, please select the wrong statement:a. Some degree of fibrosis can be observed in 75% of cases of subcutaneous sarcoidosisb. The presence of fibrosis is not significantly associated with advanced radiological stages of systemic sarcoidosisc. The presence of fibrosis is not significantly associated with . 2 years persistence of activity of systemic sarcoidosisd. The presence of fibrosis is more frequent in cases with lobular and septal involvement compared with cases with lobular

involvemente. The persistence time of subcutaneous sarcoidosis lesions is significantly longer in lesions with fibrosis




http://cme.lww.com

5. Comparing patients with lesions clinically and histopathologically similar to subcutaneous sarcoidosis who did not fulfillcriteria for systemic sarcoidosis versus patients with systemic sarcoidosis and subcutaneous sarcoidosis, there were significantdifferences in:a. Ageb. Presence of fibrosisc. Presence of fibrinoid necrosisd. Lymphocyte densitye. No significant differences were detected between both

groups of patients




ANSWER SHEET FOR THE AMERICAN JOURNAL OF DERMATOPATHOLOGYCME PROGRAM EXAM

APRIL 2020Please answer the questions on pages 241-242 by filling in the appropriate circles on the answer sheet below. Mark the one best answer and fill in the circle until the letter is no longer visible. To process your exam, you must also provide the following information:Name (please print):Street AddressCity/State/ZipDaytime PhoneSpecialty

Your evaluation of this CME activity will help guide future planning. Please respond to the following questions below.

Please rate these activities 1 (minimally) to 5 (completely):These activities were effective in meeting the educational objectives.These activities were appropriately evidence-based.These activities were relevant to my practice.

Please rate your ability to achieve the following objectives, both before and after this activity:1 (minimally) to 5 (completely)

After completing this CME activity, physicians should be better able to:

Do you expect that these activities will help you improve your skill or judgment within the next 6 months? (1 — definitely will not change, 5 — definitely will change)

How will you apply what you learned from these activities? (Mark all that apply).

Please list at least one (1) change you will make to your practice as a result of this activity:

[ ] Yes! I am interested in receiving future CME programs from Lippincott CME Institute! (Please place a check mark in the box.)

Did you perceive any bias for or against any commercial products or devices? Yes NoIf yes, please explain:

How long did it take you to complete these activities? ______hours ______minutes What are your biggest clinical challenges related to dermatopathology?

How committed are you to applying this activity to your practice in the ways you indicated above?(1 — definitely will not change, 5 — definitely will change)

O In diagnosing patientsO In monitoring patientsO In educating students and colleaguesO As part of the quality or performance improvement projectO For maintenance of board certification

O In making treatment decisionsO As a foundation to learn moreO In educating patients and their caregiversO To confirm current practiceO For maintenance of licensure

How many patients are likely to be impacted by what you learned from this activity?O <20% O 20-40% O 40-60% O 60-80% O >80%

A B C DA B C DA B C D

1.2.3.

A B C D4.A B C D5.

Mail the completed Answer Sheet and a check or money order for the $15 processing fee by March 31, 2022 to:Lippincott CME Institute, Inc.

Wolters Kluwer HealthTwo Commerce Square

2001 Market Street, 3rd FloorPhiladelphia, PA 19103

1 2 3 4 5O O O O O

1 2 3 4 5O O O O O

1 2 3 4 5O O O O O

O O

O O O O OO O O O O

1 2 3 4 5O O O O O

O O O O O

Pre1 2 3 4 5O O O O O

O O O O O

Post

1. Identify the histopathological features of subcutaneous sarcoidosis.

2. Assess the presence of fibrosis in subcutaneous sarcoidosis and its relationship with the clinical features of systemic sarcoidosis.

EEEEE




histopathological features of subcutaneous sarcoidosis

Documents