Seminars in Diagnostic Pathology 34 (2017) 261–272

Contents lists available at ScienceDirect

Seminars in Diagnostic Pathology

journal homepage: www.elsevier.com/locate/serndb

Panniculitis: A summary
Mark R. Wick n
Section of Dermatopathology,Dermatopathology, Division of Surgical Pathology & Cytopathology, University of Virginia Medical Center, Charlottesville, VA, USA

art ic l e i nf o a b s t r a c t

The diagnosis of panniculitis is felt to be a confusing topic by some pathologists. This summarical article
Keywords: presents inflammatory diseases of the subcutis in a systematic fashion, based on whether they are
Pannniculitis centered on fibrovascular septa or the adipose lobules, and whether morphologic vasculitis is present or
Vasculitis not. Septocentric, non-vasculitis disorders include erythema nodosum, panniculitis that follows the use
Erythema nodosum of “biological” therapeutic agents, lipodermatosclerosis, post-irradiation panniculitis, morphea profunda,
Lipodermatosclerosis and necrobiosis lipodica profunda. Polyarteritis nodosa and Behçet's disease are the conditions that are
Post-irradiation panniculitis based in the subcutaneous septa with vasculitis. Predominantly-lobular panniculitides with no vasculitis
Morphea profunda
include pancreatogenic panniculitis, the panniculitis of alpha-1-antitrypsin deficiency, panniculitis as-
Behçet disease
sociated with lupus erythematosus and dermatomyositis, subcutaneous Sweet syndrome, eosinophilic
Polyarteritis nodosa
Necrobiosis lipoidica panniculitis, factitial panniculitis, cold panniculitis, panniculitis following injections of corticosteroids,
Erythema induratum, pancreatogenic pan- lipomembranous (ischemic) panniculitis; sclerema neonatorum and subcutaneous fat necrosis of the
niculitis newborn, and Rosai-Dorfman disease of the subcutis. Erythema induratum and infectious panniculitis
Alpha-1-antitrypsin deficiency are vasculitic and lobulocentric conditions. This article reviews the histological features of these diseases.
Lupus erythematosus & 2017 Elsevier Inc. All rights reserved.
Dermatomyositis
Sweet syndrome
Infectious panniculitis
Eosinophilic panniculitis
Factitial panniculitis
Cold panniculitis
Sclerema neonatorum
Subcutaneous fat necrosis of the newborn

The diagnosis of panniculitis is regarded as a bewildering subject Primarily-septal panniculitides

by some pathologists. Potentially-shared histological patterns are
common to several clinical disorders in that category of diseases,
and some individual panniculitides also are capable of assuming
more than one microscopic appearance. This fact relates to the
reality that most inflammatory diseases of the panniculus begin as
neutrophilic infiltrates and may then “mature” into conditions with
dissimilar, largely-mononuclear histologic components 1,2.
As outlined by Prieto & Ivan, inflammatory diseases of the fat are
primarily categorized by their microanatomical features, as septal—
centered on the interlobular fibrovascular septa in the subcutis—or
lobular, involving the adipose lobules themselves (Tables 1 and 2). In
turn, that distribution relates to the sizes of the blood vessels on
which the inflammation is focused. Septal disorders target large- and
medium-sized vascular structures, whereas lobular lesions principally
involve small vessels 3. They can be further subclassified using clinical
data and more detailed histological information (Figs. 1 and 2).
n
Coorrespondence address: University of Virginia Hospital, Room 3020, 1215 Lee
Street, Charlottesville, VA 22908-0214, USA.
E-mail address: mrwick1@usa.net
Principally-septal panniculitides without vasculitis
Erythema nodosum
Erythema nodosum (EN) is the most commonly-encountered
form of panniculitis. It is mainly seen in women during early
adulthood, manifesting with several nodular, reddish, minimally-
tender lesions that usually involve the anterior surfaces of the legs.
Less often, other skin areas may be involved as well 4–9. Malaise,
low-grade fever, and leukocytosis may be present. The duration of
EN varies from several weeks to several years, but the disorder is
ultimately self-limited 4. It is potentially associated with under-
lying infections– which may be bacterial, viral, fungal, or chla-
mydial– or with sarcoidosis and hematolymphoid diseases 10.
The microscopic image of EN is that of septal edema or fibrosis,
and a mixed cellular infiltrate that potentially includes erythrocytes,
neutrophils and eosinophils (in early lesions), lymphocytes, and
histiocytes (Fig. 3). Non-necrotizing septal microgranulomas are ty-
pical of fully-evolved lesions, including “Miescher” granulomas that
are centered on small blood vessels or slit-like virtual spaces 7. His-
tological findings that tend to militate against a diagnosis of EN

http://dx.doi.org/10.1053/j.semdp.2016.12.004
0740-2570/& 2017 Elsevier Inc. All rights reserved.
262 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272

Table 1 the lesions resemble those of deep morphea or systemic sclerosis,

Predominantly-septal panniculitides. being depressed, discolored, and “hide-bound” areas in the skin.
 Histologically, one sees sclerotic thickening of the subcuticular fi-
Erythema nodosum
 Panniculitis following use of “biological” therapeutic agents brous septa, with a variable lymphoplasmacytic infiltrate. Lipo-
 Lipodermatosclerosis (sclerosing panniculitis) phagic granulomas also may be present in the fat lobules. The
 Post-irradiation panniculitis overlying corium contains sclerotic blood vessels with intimal fi-
 Morphea profunda
broplasia, and atypical polyploid dermal fibroblasts with pleo-
 Behcet's disease
 Polyarteritis nodosa morphic, hyperchromatic nuclei 12.
 Necrobiosis lipoidica Morphea profunda (subcutaneous morphea) has closely-similar
clinical and histologic appearances 13,14 (Fig. 4). It is not possible to
separate that condition definitively from post-irradiation panni-
culitis, even in patients with a history of that therapeutic
intervention.
Table 2
Predominantly-lobular panniculitides.
Subcuticular necrobiosis lipoidica
 Erythema induratum (Bazin disease; nodular vasculitis)n Necrobiosis lipoidica (NL) has been discussed separately in
 Pancreatic panniculitis another article in this issue of Seminars. In some examples of that
 Alpha 1-antitrypsin deficiency panniculitis
 disorder, it extends beyond the deep dermis into the subcutis,
Panniculitis in lupus erythematosus & dermatomyositis
 “Atypical lymphocytic lobular panniculitis” where it principally affects the septa with lesser lobular involve-
 Subcutaneous Sweet syndrome ment. Necrobiotic granulomas, lymphohistiocytic infiltrates, and
 Infectious panniculitides* fibrosis typify the lesions histologically 15–17 (Fig. 5). The epicenter
 Eosinophilic panniculitis (including Churg-Strauss syndrome*)
of NL is in the mid-dermis, and the entirety of the corium is
 Factitial panniculitis
 Cold panniculitis characteristically involved by granulomatous inflammation.
 Sclerema neonatorum
 Subcutaneous fat necrosis of the newborn Lipodermatosclerosis (sclerosing panniculitis)
 Panniculitis following steroid injections Lipodermatosclerosis (LDS) is synonymous with “sclerosing
 Lipomembranous (ischemic) panniculitis
 Rosai-Dorfman disease
panniculitis.” It is seen in the lower legs, principally in obese pa-
tients who have venous insufficiency. The skin is grossly indurated
n
Vasculitis is present in these disorders. and shiny, with increased pigmentation or erythema. The legs
often macroscopically resemble inverted champagne bottles or
include morphological vasculitis, necrosis, and an overriding dom- upside-down bowling pins, because the circumference of the
inance of epithelioid granulomas 3. distal lower extremities is diminished 18–21.
Lesions that are virtually identical to those of EN can be seen Histologically, LDS demonstrates septal fibrosis and mild lym-
after the administration of “biological” therapeutic agents 11. Those phoplasmacytic inflammation, with sclerosis of blood vessels.
include such drugs as adalimumab, imatinib, BRAF inhibitors, and Atrophy of fat lobules may be seen, and the dermis often exhibits
immune checkpoint modulators. the morphological changes of vascular stasis 18,19,21.

Post-irradiation panniculitis & morphea profunda Principally-septal panniculitides with vasculitis

Panniculitis may follow the administration of radiotherapy,
within the radiation field, months or years thereafter. Clinically, Only two forms of panniculitis feature septocentricity together

Fig. 1. Algorithm for the diagnosis of predominantly-septal panniculitides.

 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272 263

Fig. 2. Algorithm for the diagnosis of predominantly-lobular panniculitides.

Fig. 3. Erythema nodosum produces nodular reddish subcutaneous nodules, usually on the anterior lower legs (top left). The septal distribution of inflammation in this
disorder is shown in the top right & bottom left panels. It principally comprises lymphocytes and histiocytes in well-developed lesions, sometimes with multinucleated giant
cells (bottom right panel).
264 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272

Fig. 4. Morphea profunda of the thigh is seen in the upper left panel, manifested by discolored and depressed areas in the skin. Microscopically, it exhibits dense fibrosis of
the subcutaneous septa, together with lymphohistiocytic infiltrates (right panels).

Fig. 5. Necrobiosis lipoidica presents with indurated and red-brown plaques, usually on the shins (left panel). When it involves the hypodermis, subcutaneous septa are
fibrotic and they also show lymphohistiocytic infiltrates with necrobiosis (right panels).

with vasculitis. They are polyarteritis nodosa (PAN) and involve-
ment of the subcutis by Behçet s disease (BD). Clinically, both of
those diseases present with cutaneous ulcers in adults, with or
without tender nodular reddish subcutaneous nodules. PAN is often
further characterized by livedo reticularis, myalgias, neuropathy,
hypertension, renal insufficiency, infection by the hepatitis B virus,
and the formation of aneurysms in visceral arteries. The lungs are
unaffected. On the other hand, BD is associated with mucocutaneous,
ocular, cardiovascular, renal, gastrointestinal, pulmonary, urologic,
and central nervous system lesions, as well as involvement of the
joints and lungs. Mucocutaneous ulcers in BD are aphthous in nature,
with common localization in the oral mucosa and genital skin 17,22.
Histologically, the most consistent difference between PAN and
BD is the nature of the inflammatory cells that effect the vasculitic
lesions. PAN is typified by transmural neutrophilic infiltrates of large,
medium-sized, and small arteries, together with fibrinoid change of
the vascular media (Fig. 6). In contrast, BD usually features a lym-
phocytic vasculitis that principally affects small arteries and veins
without fibrin deposition (Fig. 7). Uncommonly, a leukocytoclastic
venulitis may be present in that condition instead 2,17,23.
 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272 265

Fig. 6. Polyarteritis nodosa (PAN) is shown here, with ulcers and confluent zones of cutaneous induration on the lower legs (left panel). Microscopically, PAN affects large
blood vessels in the subcutaneous septa, which show neutrophilic vasculitis and fibrinoid change (right panels).

Fig. 7. Behcet's panniculitis (BP) is shown at the top left, with multiple reddish nodules in the subcutis of the lower legs. Microscopically, BP is centered on the subcutaneous
septa (top right), and it shows the presence of lymphocytic vasculitis (bottom panels).

Primarily-lobular panniculitides
Principally-lobular panniculitis with vasculitis
Erythema induratum and infections account for the principally-
lobular forms of panniculitis that include morphologic vasculitis.
Erythema Induratum (nodular vasculitis; bazin disease)
Erythema induratum (EI) mainly affects the subcutis of the
lower legs in middle-aged or elderly women; men are more un-
commonly affected 18,23–26. This disease is still considered to be a
form of “tuberculid” (an immune reaction in the skin to infection
with Mycobacterium tuberculosis) by many observers, together
with lichen scrofulosorum and papulonecrotic tuberculid 27. An
alternate view is that EI represents a generic cutaneous vasculitis
pattern with several potential etiologies, only one of which is tu-
berculous in nature; infection with the hepatitis C virus and in-
flammatory bowel disease have also been implicated in some
instances 18,23,24,28.
EI presents with multiple reddish, tender plaques and nodules
that often ulcerate, in patients who are otherwise well. This con-
dition follows a cyclic course, with spontaneous involution and
266 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272
Fig. 8. Erythema induratum (nodular vasculitis; Bazin disease) typically causes ulcerating nodular lesions in the hypodermis of the lower legs, usually in middle-aged or
elderly women (top left panel). It manifests histologically with a lobulocentric lymphohistiocytic infiltrate (top right), with vasculitis (bottom left) and potentially-necro-
tizing granulomatous inflammation (bottom right).
then recurrence of the lesions over months to years. Appropriate
treatment of associated infections—if any can be identified—is
usually undertaken, and local injections of corticosteroids into the
lesions have been used as well 24,25.
A histopathologic study of several cases of EI by Schneider &
Jordaan 29 showed the presence of diffuse lobular panniculitis,
with lesser septal involvement. A primary neutrophilic or lym-
phocytic vasculitis of large or small subcutaneous vessels was
present, together with varying combinations of acute and chronic
inflammation in the fat lobules with coagulative and caseating-
type necrosis and granulomatous inflammation (Fig. 8). Ill-formed
granulomas were the most common, but palisading and lipophagic
granulomatous lesions also were observed. Immunostaining de-
monstrated the presence of antigen-presenting cells, macro-
phages, and T-lymphocytes. In other analyses, studies of EI lesions
with the polymerase chain reaction have demonstrated myco-
bacterial antigens in a significant proportion of cases 23.
Infectious panniculitides
The topic of infectious panniculitis (IP) has been reviewed by
Morrison et al. It can be seen as a primary process in the subcutis
after direct inoculation of microbes by trauma or direct extension
from a cutaneous or deep soft tissue infection. Alternatively, sec-
ondary IP results from the hematogenous spread of a systemic
infection. Several potential anatomical sites for IP have been de-
scribed, but it usually affects the extremities and truncal skin.
Many patients with IP are immunocompromised or they are in-
travenous drug abusers 30,31.
Clinically, the lesions of IP may resemble those of EN, or they
may be larger, more erythematous, and potentially-ulcerated. Fe-
ver and general malaise are common coincident findings 32. Many
possible pathogens can be identified by formal culturing of the
lesions or microscopic examination of biopsy specimens. They
include several bacteria (Streptococcus; Staphyloccus; Pseudomo-
nas; typical and atypical Mycobacteria; Actinomyces; Hemophilus;
Nocardia; Klebsiella; Acinetobacter; and Borrelia); fungi (Sporothrix;
Fonsecaea; Phialophora; Rhinocladiella; Cladophialophora; Madur-
ella; Acremonium; Curvularia; Pseudallescheria; Blastomyces; Histo-
plasma; Cryptococcus; Penicillium; Aspergillus; Fusarium; and Can-
dida); parasitic organisms (Leishmania; Toxoplasma; Spirometra;
and Gnathostoma); and cytomegalovirus 30,33,34.
Histologically, IP manifests with mixed inflammatory infiltrates
which are centered in the subcutaneous lobules. Neutrophils
usually predominate, but they are often admixed with granulomas
and lymphocytes. Morphological vasculitis can be seen that affects
large and small vessels alike, sometimes with fibrinoid changes.
Obviously, histochemical assessment is necessary in all potential
cases of IP, including tissue Gram, periodic acid-Schiff, Gomori
methenamine-silver, acid-fast, and Giemsa stains 30,31.
Principally-lobular panniculitis without vasculitis
Even though EN—a principally-septal process—is the most com-
monly-encountered form of panniculitis overall, the list of lobular
and non-vasculitic panniculitides is numerically more extensive than
that of the septocentric conditions. It encompasses subcutaneous
inflammation associated with pancreatic diseases; α 1-antitrypsin
deficiency; lupus erythematosus & dermatomyositis; atypical lym-
phoid infiltrates; Sweet syndrome; eosinophilic infiltrates; factitial
injuries; exposure to the cold; degenerative conditions of infancy;
prior steroid injections; ischemia; and Rosai-Dorfman disease.
 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272
Pancreatogenic panniculitis
Rarely, patients with pancreatitis (acute or chronic), pancreatic
pseudocysts, or pancreatic neoplasms may develop a singular form
of lobular panniculitis 35–38. Current thinking holds that elevated
plasma levels of lipase and amylase cause these lesions by enzy-
matic alteration of subcuticular adipose tissue. Dhawan et al.
showed that intracellular immunohistochemical labeling for pan-
creatic lipase was present in this disorder 39.
Pancreatogenic panniculitis (PP) typically affects the lower legs
of adults, where several variably-tender reddish nodules appear.
This condition may be seen several weeks before or after the
pancreatic abnormality is recognized. Acinar-cell carcinoma is the
specific tumor type that most often is associated with neoplastic
PP 38. If the underlying glandular disease remits or is extirpated
surgically, the panniculitis usually regresses but may leave residual
foci of organized fat necrosis in the subcutis 35.
Histopathologically, PP shows moderate lobular neutrophilia,
with lesser numbers of lymphocytes and necrosis of adipocytes.
The damaged fat cells contain finely-granular basophilic cyto-
plasmic material, representing calcium “milk” 35,36 (Fig. 9). Overt
foci of dystrophic calcification also are common, as are “ghost-like”
outlines of necrotic fat cells.
Panniculitis in α 1-antitrypsin deficiency
Panniculitis in patients with alpha-1-antitrypsin deficiency
(AATD) is rare, with an estimated prevalence of 0.1% in individuals
who have a marked diminution of functional enzymatic activity
(typically with the PiZZ genotype) 40–45. Clinically, this disorder
presents with tender and ulcerating reddish subcutaneous no-
dules; panniculitis may be the only sign of AATD, or it can be ac-
companied by panacinar emphysema or hepatic dysfunction (or
Fig. 9. The panniculitis of pancreatic disease presents with tender red-brown plaques and nodules (left panel). Histologically, one sees fat necrosis with “ghost” adipocytes
and calcification (right panels).
267
both) as well. The skin lesions remit after intravenous infusions of
exogenous α 1-antitrypsin 45.
Histologically, AATD panniculitis exhibits neutrophilic in-
filtrates in the deep corium and subcuticular adipose lobules, with
zones of fat necrosis (Fig. 10). Septal inflammation is often present
as well 46. Geller & Su 47 noted that neutrophils are also present
between collagen bundles in the reticular dermis in this condition,
with incipient necrobiosis.
Lymphocytic panniculitis in connective tissue disorders & lymphoid
dyscrasia
Patients with systemic or discoid lupus erythematosus (LE) or
dermatomyositis (DM) develop panniculitis (lupus profundus) in a
minority of cases, and it may rarely be the seminal manifestation
of those disorders 48–54. The more common clinical and histolo-
gical findings in those conditions have been reviewed in another
paper in this issue.
The microscopic features of panniculitis in patients with LE or
DM are comparable. They include diffuse lobular infiltrates of
mature lymphocytes with no nuclear atypicality, associated with
multifocal hyalinization of the subcuticular fat 51,52 (Fig. 11).
Another consideration has been described by Magro et al., in
reference to a disorder termed “atypical lobular lymphocytic
panniculitis” (ALLP) 55. The latter condition resembles lupus
profundus histologically, but it shows clonality in genotypic
studies and presumably represents a form of quasi-neoplastic
lymphoproliferation (“lymphoid dyscrasia”) 56. Practically speak-
ing, there would appear to be no compelling reason to look for
T-cell receptor gene rearrangements in all cases of lymphocytic
panniculitis, because the clinical evolution of ALLP has typically
been self-limiting rather than progressive 55,56. As outlined by
268 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272

Fig. 10. Alpha-1-antitrypsin deficiency-related panniculitis causes reddish brown nodules in the subcutis that may ulcerate (left). Microscopically, it is represented by a
predominantly-lobular neutrophilic infiltrate with fat necrosis (right).

Shiau & colleagues, such studies are most appropriate when the
morphological features of a lymphocyte-predominant pannicu-
litis suggest the likely presence of subcutaneous panniculitis-like
T-cell lymphoma or cutaneous γ- δ-cell lymphoma, which are
also clonal proliferations but which feature the presence of vas-
culitis-like foci 57–59.
Cold-induced panniculitis
A form of panniculitis may be seen as an idiosyncratic response to
cold exposure. It is most often encountered in children, or in adults
who spend prolonged periods of time in the cold, affecting skin areas
that are exposed to the environment 60–62. The histological features of
cold panniculitis closely parallel those of LE/DM panniculitis, and
therefore the clinical history is paramount in separating those disorders
from one another. In some cases of cold panniculitis, chronic in-
flammation is particularly dense at the dermal-subcuticular interface 60.
Subcutaneous Sweet Syndrome
Sweet syndrome (acute aseptic neutrophilic dermatosis) has
also been discussed elsewhere in this installment of Seminars. The
dense dermal infiltrate of polymorphonuclear leukocytes which
characterizes that disease may extend into the subcutaneous lo-
bules (and septa) as well, representing a specific form of neu-
trophilic panniculitis. Uncommonly, small-vessel vasculitis in the

Fig. 11. Lupus erythematosus panniculitis (lupus profundus) presents with reddish nodules and depressed sclerotic plaques (left). The histologic image of that disease
features lobular lymphocytic infiltration with hyalinization of the adipose tissue (right).
 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272 269

Fig. 12. Eosinophilic panniculitis is no different clinically from other forms of panniculitis (left), and it has several potential etiologies. This condition is represented by diffuse
lobular infiltration of the subcutis by eosinophils (right).

Fig. 13. Both subcutaneous fat necrosis of the newborn, shown here (left) and sclerema neonatorum are seen in infants. Both disorders feature the presence of crystal-like
inclusions in the subcutis microscopically (right), but they have dissimilar clinical evolutions.

63
subcutis may be present in this condition as well
Eosinophilic Lobular Panniculitis
Diffuse lobulocentric infiltrates of eosinophils in the superficial
adipose tissue (Fig. 12) can be associated with a spectrum of
etiologies. They potentially include drug eruptions; reactions to
arthropod bites; a manifestation of parasitosis (e.g., sparganosis;
gnathostomiasis); Churg-Strauss disease; Shulman syndrome;
Kikuchi disease, hypereosinophilic syndrome, and Kimura
. disease 64–67. Hence, “eosinophilic panniculitis” is a descriptive
term rather than a specific entity.
Factitial panniculitis
Individuals with variants of the Munchhausen syndrome or
other psychological disturbances may surreptitiously inject foreign
materials (various chemicals; food; plant materials; feces; urine)
into the subcutis for secondary emotional gain 68–70. The resulting
lesions, known as factitial panniculitis, can be challenging to
270 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272

Fig. 14. Lipomembranous panniculitis (membranous lipodystrophy; membranocystic fat necrosis) usually affects the lower legs (left). Histologically, it causes microcystic
change in the subcutis (top right), and “feathery” membranous alteration in adipocytes (bottom right).

Fig. 15. The macroscopic appearance of Rosai-Dorfman disease in the subcutis is shown in the left panel, represented by several nodules. Histologically, one sees either
lobular or lobular & septal lymphohistiocytic infiltrates (top right). Constituent histiocytes demonstrate lymphemperipolesis (bottom right).

recognize histopathologically because they present a diverse
group of microscopic appearances. Usually, lobular inflammation
is dominant, often including multinucleated foreign body-type
giant cells, and polarizable material may be present 68.
Panniculitis following exogenous steroid injection
The chemical “carriers” of injectable corticosteroid preparations
may likewise induce a form of panniculitis that shows a micro-
scopic overlap with the factitial type. Sometimes, microscopic
collections of amorphous amphophilic material may be present in
the subcutaneous fat as well 71. Once again, clinical information is
vital to recognizing this condition.
Panniculitides of infancy—subcutaneous fat necrosis & sclerema
neonatorum
Two forms of panniculitis are histologically-singular, because they
feature the presence of crystal-like inclusions within a mixed in-
flammatory infiltrate in the subcutis, potentially also with multinucleated
 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272
giant cells. These conditions—subcutaneous fat necrosis of the newborn
(SFNN) and sclerema neonatorum (SN)—are basically indistinguishable
from one another microscopically (Fig. 13). However, SFNN is seen in full-
term infants who are otherwise healthy, and it is self-limited. On the
other hand, SN occurs in premature, ill babies who develop widespread
sclerosis of the subcutis, and it is usually fatal 72.
Lipomembranous (ischemic) panniculitis
Another form of histologic alteration in lobules of the subcutis
may be seen as an idiopathic condition 73,74, or in the context of
other, more specific illnesses 75. It is typified by a peculiar “feathery”
degeneration within adipocytes, known as lipomembranous change
(Fig. 14), along with the formation of cystic spaces in the fat. In-
flammation is minimal and lymphohistiocytic in character, and septal
fibrosis also may be present 74. This disorder—variously known as
lipomembranous panniculitis (LMP), membranocystic fat necrosis, or
lipomembranous dystrophy—is principally seen in the form of de-
pressed, sclerotic plaques in obese patients with venous insufficiency
of the legs. Because of those associations, an ischemic pathogenesis is
suspected 73,74. The membranocystic changes in LMP are not specific;
as documented by Snow & Su 74, they also may be observed in some
examples of EN, morphea profunda, lupus panniculitis, or sub-
cutaneous necrobiosis lipoidica.
Subcutaneous Rosai-Dorfman disease
The subcutis may be involved primarily or exclusively in pa-
tients who have sinus histiocytosis with massive lymphadeno-
pathy, otherwise known as Rosai-Dorfman disease (RDD) 76–81. It
presents with reddish nodules and plaques that can be seen in any
area of the skin, at any age, and is thought to be the result of
spontaneous immune dysregulation. In 20–25% of cases, cutaneous
disease is unaccompanied by lesions anywhere else 81.
Microscopically, RDD may be exclusively lobular in distribution in
the subcutaneous fat, or it may involve the septa as well (Fig. 15).
Dense lymphohistiocytic infiltrates are present together with zones
of fibrosis. The constituent histiocytes are unique because their cy-
toplasm contains intact lymphocytes (“lymphemperipolesis”); they
are also immunoreactive for S100 protein 76.
References
1. Chan MP. Neutrophilic panniculitis: algorithmic approach to a heterogeneous
group of disorders. Arch Pathol Lab Med 2014;138:1337–1348.
2. Prieto VG, Ivan D. Panniculitis: a diagnostic algorithm. Diagn Histopathol
2009;15:195–202.
3. Segura S, Requena L. Anatomy and histology of normal subcutaneous fat, ne-
crosis of adipocytes, and classification of the panniculitides. Dermatol Clin
2008;26:419–424.
4. Blake T, Manahan M, Rodins K. Erythema nodosum: a review of an uncommon
panniculitis. Dermatol Online J 2014;20(4):22376 [E-publication][PMID:
24746312].
5. Passarini B, Infusino SD. Erythema nodosum. G Ital Dermatol Venereol
2013;148:413–417.
6. Mana J, Marcoval J. Erythema nodosum. Clin Dermatol 2007;25:288–294.
7. Requena L, Sanchez-Yus E. Erythema nodosum. Semin Cutan Med Surg
2007;26:114–125.
8. Ter Poorten MC, Thiers BH. Panniculitis. Dermatol Clin 2002;20:421–433.
9. Requena L, Requena C. Erythema nodosum. Dermatol Online J 2002;8(1):4 [E-
publication][PMID: 12165214].
10. Cribier B, Caille A, Heid E, Grosshans E. Erythema nodosum and associated
diseases: a study of 129 cases. Int J Dermatol 1998;37:667–672.
11. Mossner R, Zimmer L, Berking C, et al. Erythema nodosum-like lesions during
BRAF inhibitor therapy: report on 16 new cases and review of the literature. J
Eur Acad Dermatol Venereol 2015;29:1797–1806.
12. Pielasinki U, Machan S, Camacho D, et al. Postirradiation pseudoscler-
odermatous panniculitis: three new cases with additional histopathologic
features supporting the radiotherapy etiology. Am J Derm 2013;35:129–134.
13. Bielsa I, Ariza A. Deep morphea. Semin Cutan Med Surg 2007;26:90–95.
14. Balabanova M, Obreshkova E. Scleroderma profunda: clinicopathological stu-
dies. Adv Exp Med Biol 1999;455:105–109.
15. Requena L, Sanchez-Yus E. Panniculitis. Part I: mostly-septal panniculitis. J Am
Acad Dermatol 2001;45:163–183.
271
16. Peyri J, Morano A, Marcoval J. Necrobiosis lipoidica. Semin Cutan Med Surg
2007;26:87–89.
17. Rashtak S, Pittelkow MR. Skin involvement in systemic autoimmune diseases.
Curr Dir Autoimmun 2008;10:344–358.
18. White WL, Wieselthier JS, Hitchcock MG. Panniculitis: recent developments
and observations. Semin Cutan Med Surg 1996;15:278–299.
19. Miteva M, Romanelli P, Kirsner RS. Lipodermatosclerosis. Dermatol Ther
2010;23:375–388.
20. Smith PC. The causes of skin damage and leg ulceration in chronic venous
disease. Int J Low Extrem Wounds 2006;5:160–168.
21. Demitsu T, Okada O, Yoneda K, Manabe M. Lipodermatosclerosis: report of
three cases and review of the literature. Dermatology 1999;199:271–273.
22. Uva L, Miguel D, Pinheiro C, Filipe P, Freitas JP. Mucocutaneous manifestations
of Behçet's disease. Acta Reum Port 2013;38:77–90.
23. Ferrara G, Stefanato CM, Gianotti R, Kubba A, Annessi G. Panniculitis with
vasculitis. G Ital Dermatol Venereol 2013;148:387–394.
24. Mascaro Jr JM, Basalga E. Erythema induratum of Bazin. Dermatol Clin
2008;26:439–445.
25. Phelps RG, Shoji T. Update on panniculitis. Mt Sinai J Med 2001;68:262–267.
26. Requena L, Sanchez-Yus E. Panniculitis. Part II: mostly-lobular panniculitis. J Am
Acad Dermatol 2001;45:325–361.
27. Braun-Falco O, Thomas P. The tuberculid concept from the current viewpoint.
Hartarzt 1995;46:383–387.
28. Misago N, Narisawa Y. Erythema induratum (nodular vasculitis) associated
with Crohn's disease: a rare type of metastatic Crohn's disease. Am J Derm
2012;34:325–329.
29. Schneider JW, Jordaan HF. The histopathologic spectrum of erythema in-
duratum of Bazin. Am J Derm 1997;19:323–333.
30. Morrison LK, Rapini R, Willison CB, Tyring S. Infection and panniculitis. Der-
matol Ther 2010;23:328–340.
31. Patterson JW, Brown PC, Broecker AH. Infection-induced panniculitis. J Cutan
Pathol 1989;16:183–193.
32. Delgado-Jimenez Y, Fraga J, Garcia-Diez A. Infective panniculitis. Dermatol Clin
2008;26:471–480.
33. Griffin MP, Tompkins KJ, Ryan MT. Cutaneous sparganosis. Am J Derm
1996;18:70–72.
34. Ollague W. Gnathostomiasis (nodular migratory eosinophilic panniculitis). J Am
Acad Dermatol 1985;13:835–836.
35. Rongioletti F, Caputo V. Pancreatic panniculitis. G Ital Dermatol Venereol
2013;148:419–425.
36. Garcia-Romero D, Vanaclocha F. Pancreatic panniculitis. Dermatol Clin
2008;26:465–470.
37. Martin SK, Agarwal G, Lynch GR. Subcutaneous fat necrosis as the presenting
feature of a pancreatic carcinoma: the challenge of differentiating endocrine
and acinar pancreatic neoplasms. Pancreas 2009;38:219–222.
38. Moro M, Moletta L, Blandamura S, Sperti C. Acinar cell carcinoma of the pan-
creas associated with subcutaneous panniculitis. JOP 2011;12:292–296.
39. Dhawan SS, Jimenez-Acosta F, Poppiti Jr RJ, Barkin JS. Subcutaneous fat necrosis
associated with pancreatitis: histochemical and electron microscopic findings.
Am J Gastroenterol 1990;85:1025–1028.
40. McElvaney NG. Diagnosing alpha-1-antitrypsin deficiency: how to improve the
current algorithm. Eur Respir Rev 2015;24:52–57.
41. Silverman E, Sandhaus R. Clinical practice: alpha-1-antitrypsin deficiency. N
Engl J Med 2009;360:2749–2757.
42. Valverde R, Rosales B, Ortiz-de-Frutos FJ, Rodriguez-Peralto JL, Ortiz-Romero PL.
Alpha-1-antitrypsin deficiency panniculitis. Dermatol Clin, 26; 2008:447–451.
43. Geraminejad P, DeBloom II JR, Walling HW, Sentheimer RD, VanBeek M. Alpha-
1-antitrypsin-associated panniculitis: the MS variant. J Am Acad Dermatol
2004;51:645–655.
44. McBean J, Sable A, Maude J, Robinson-Boston L. Alpha-1-antitrypsin deficiency
panniculitis. Cutis 2003;71:205–209.
45. Smith KC, Pittelkow MR, Su WPD. Panniculitis associated with severe alpha-1-
antitrypsin deficiency: treatment and review of the literature. Arch Dermatol
1987;123:1655–1661.
46. Blanco I, Lipsker D, Lara B, Janciauskiene S. Neutrophilic panniculitis associated
with alpha-1-antitrypsin deficiency: an update. Br J Dermatol 2016;174:753–
762.
47. Geller JD, Su WPD. A subtle clue to the histopathologic diagnosis of early alpha-
1-antitrypsin deficiency panniculitis. J Am Acad Dermatol 1994;31:241–245.
48. Kuhn A, Landmann A. The classification and diagnosis of cutaneous lupus er-
ythematosus. J Autoimmun 2014;48 & 49:14–19.
49. Yu C, Chang C, Zhang J. Immunologic and genetic considerations of cutaneous
lupus erythematosus: a comprehensive review. J Autoimmun 2013;41:34–45.
50. Weingartner JS, Zekek DC, Burkhart CN, Morrell DS. Lupus erythematosus pan-
niculitis in children: report of three cases and review of previously-reported cases.
Pediatr Dermatol, 29; 2012:169–176.
51. Fraga J, Garcia-Diez A. Lupus erythematosus panniculitis. Dermatol Clin, 26;
2008:453–463.
52. Peters MS, Su WPD. Lupus erythematosus panniculitis. Med Clin North Am, 73;
1989:1113–1126.
53. Solans R, Cortes J, Selva A, et al. Panniculitis: a cutaneous manifestation of
dermatomyositis. J Am Acad Dermatol 2002;46(Suppl 5):S148–S150.
54. Chao YY, Yang LJ. Dermatomyositis presenting as panniculitis. Int J Dermatol
2000;39:141–144.
55. Magro CM, Crowson AN, Byrd JC, Soleymani AD, Shendrik I. Atypical lympho-
cytic lobular panniculitis. J Cutan Pathol 2004;31:300–306.
272 M.R. Wick / Seminars in Diagnostic Pathology 34 (2017) 261–272
56. Magro CM, Schaefer JT, Morrison C, Porcu P. Atypical lymphocytic lobular
panniculitis: a clonal subcutaneous T-cell dyscrasia. J Cutan Pathol
2008;35:947–954.
57. Shiau CJ, Abi-Daoud MS, Wong M, Crawford RI. Lymphocytic panniculitis: an
algorithmic approach to lymphocytes in subcutaneous tissue. J Clin Pathol
2015;68:954–962.
58. Magro CM, Wang X. Indolent primary cutaneous gamma-delta T-cell lympho-
ma localized to the subcutaneous panniculus and its association with atypical
lymphocytic lobular panniculitis. Am J Clin Pathol 2012;138:50–56.
59. Guitart J. Subcutaneous lymphoma and related conditions. Dermatol Ther
2010;23:350–355.
60. Quesada-Cortes A, Campos-Munoz L, Diaz-Diaz RM, Casado-Jimenez M. Cold
panniculitis. Dermatol Clin 2008;26:485–489.
61. Lowe LB. Cold panniculitis in children. Am J Dis Child 1968;115:709–713.
62. West SE, McCalmont TH, North JP. Ice-pack dermatosis: a cold-induced der-
matitis with similarities to cold panniculitis and perniosis that histopatholo-
gically resembles lupus. JAMA Dermatol 2013;149:1314–1318.
63. Guhl G, Garcia-Diaz A. Subcutaneous Sweet syndrome. Dermatol Clin
2008;26:541–551.
64. Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and
evolution. J Am Acad Dermatol 1996;34:229–234.
65. Boroni G, Torti S, D’Ospina RM, Pezzini C. Drug-induced panniculitides. G Ital
Dermatol Venereol 2004;149:263–270.
66. Cho KH, Kim YG, Yang SG, Lee DY, Chung JH. Inflammatory nodules of the lower
legs: a clinical and histological analysis of 134 cases in Korea. J Dermatol
1997;24:522–529.
67. Maleki D, Sayyah A, Rahimi-Rad MH, Gholemi N. Kimura's disease with eosi-
nophilic panniculitis, treated with cyclosporine: a case report. Allergy Asthma
Clin Immunol 2010;6:5 [E-publication; PMID 20236545].
68. Sanmartin O, Requena C, Requena L. Factitial panniculitis. Dermatol Clin
2008;26:519–527.
69. Falagas ME, Christopoulou M, Resmarakis ES, Vlastou C. Munchausen's syn-
drome presenting as severe panniculitis. Int J Clin Pr 2004;58:720–722.
70. Oh CC, McKenna DB, McLaren KM, Tidman MJ. Factitious panniculitis mas-
querading as pyoderma gangrenosum. Clin Exp Dermatol 2005;30:253–255.
71. Kwon EJ, Emanuel PO, Gribetz CH, Mudgil AV, Phelps RG. Poststeroid panni-
culitis. J Cutan Pathol 2007;34(Suppl 1):64–67.
72. Grassi S, Borroni RG, Brazzelli V. Panniculitis in children. G Ital Dermatol Ve-
nereol 2013;148:371–385.
73. Akpinar F, Demir E, Apa DD. Membranous lipodystrophy: case report and re-
view of the literature. Bras Dermatol 2015;90(3 Suppl 1):115–117.
74. Snow JL, Su WPD. Lipomembranous (membranocystic) fat necrosis: clin-
icopathologic correlation of 38 cases. Am J Derm 1996;18:151–155.
75. Chun SI, Chung KY. Membranous lipodystrophy: secondary type. J Am Acad
Dermatol 1994;31:601–605.
76. Frater JL, Maddox JS, Obadiah JM, Hurley MY. Cutaneous Rosai-Dorfman dis-
ease: comprehensive review of cases reported in the medical literature since
1990 and presentation of an illustrative case. J Cutan Med Surg 2006;10:281–
290.
77. Coras B, Michel S, Landthaler M, Hohenleutner U. Rosai-Dorfman disease with
cutaneous manifestation (sinus histiocytosis with massive lymphadenopathy).
Eur J Dermatol 2006;16:293–296.
78. Child FJ, Fuller LC, Salisbury J, Higgins EM. Cutaneous Rosai-Dorfman disease.
Clin Exp Dermatol 1998;23:40–42.
79. Van Zander J. Cutaneous Rosai-Dorfman disease. Dermatol Online J 2004;30
(3):12 [E-publication; PMID 15748582].
80. Sagi M, Marcus BS, Gat A, Martinez-de-Morentin H, Sprecher E, Goldberg I. A 60
year old woman with subcutaneous nodules on the thigh. Clin Exp Dermatol
2012;37:448–449.
81. Cook-Norris RH, Hayes BB, Robb C, Boyd AS, Zic JA. Purely cutaneous Rosai-
Dorfman disease. Int J Dermatol 2009;48:439–440.