Panniculitis

J Am Acad Dermatol. 2006 Dec;55(6):968-74. Epub 2006 Jun 21. Abstract quote

BACKGROUND: Glatiramer acetate has been shown to be effective in reducing the relapse and improving the disability of patients with multiple sclerosis. The most common adverse effects at the injection sites include pain, inflammation, and induration that spontaneously disappear within hours or a few days.

OBJECTIVE: We sought to characterize the histopathologic findings of localized panniculitis induced by glatiramer acetate at the injection sites.

METHODS: Seven patients receiving daily glatiramer acetate injections for treatment of multiple sclerosis developed localized panniculitis at the injection sites. The lesions were histopathologically and immunohistochemically studied.

RESULTS: The lesions consisted of a mostly lobular panniculitis, with lipophagic granuloma, namely histiocytes engulfing the lipids from necrotic adipocytes. In many areas, scattered neutrophils and eosinophils were seen both in the septa and in the fat lobules. Connective tissue septa showed widening and fibrosis in conjunction with many lymphoid follicles, presenting with germinal center formation. Immunohistochemically, the inflammatory infiltrate of the fat lobule consisted of CD68+ histiocytes and suppressor/cytotoxic T lymphocytes. In contrast, the lymphoid follicles in the septa and at the interface between septum and fat lobule were mainly composed of B lymphocytes.

LIMITATIONS: Only one biopsy was performed in each patient and, therefore, it was not possible to study the histopathologic evolution of the panniculitic process.

CONCLUSIONS: Localized panniculitis at the sites of subcutaneous injections of glatiramer acetate for treatment of multiple sclerosis seems to be a rare, but characteristic side effect of this therapy. The histopathologic pattern of these lesions consists of a mostly lobular panniculitis, with histiocytes and T lymphocytes in the fat lobule and thickened septa with scattered lymphoid follicles, which are mostly composed of B lymphocytes.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
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LOCATION OF INFLAMMATION	DISEASE
Predominantly Septal Panniculitis	Acrodermatitis chronica atrophicans Cytophagic histiocytic panniculitis Eosinophilic fasciitis Erythema nodosum Erythema nodosum-like Behcet's disease Factitial panniculitis Infectious panniculitis Gram-positive cocci Leukocytoclastic vasculitis Necrobiosis lipoidica Polyarteritis nodosa Scleroderma/morphea Subcutaneous granuloma annulare Sweet's syndrome Thrombophlebitis
Predominantly Lobular Panniculitis	Alpha-1 antitrypsin deficiency (A1ATD) Arthropod bite Calciphylaxis Crohn's disease Cold panniculitis Connective tissue panniculitis Cytophagic histiocytic panniculitis Dermatomyositis Eosinophilic panniculitis Erythema Induratum (Nodular Vasculitis) Erythema nodosum Erythema nodosum leprosum Erythema nodosum like Behcet disease Factitial panniculitis Gouty panniculitis Infective panniculitis Injection associated panniculitis Lipoatrophy, primary and secondary Lipodermatosclerosis Lipodystrophy syndromes Lipophagic panniculitis Lupus panniculitis Lymphoma Pancreatic panniculitis Poststeroid panniculitis Pseudolymphoma Rheumatoid arthritis-associated panniculitis Ruptured cyst Sclerema neonatorum Sclerosing lipogranuloma Silicone granuloma Subcutaneous fat necrosis of the newborn Subcutaneous sarcoidosis Sweet's syndrome Traumatic fat necrosis Weber-Christian disease Wegener granulomatosis
Predominantly Septal and Lobular	Adult lipophagic atrophic panniculitis A1ATD Arthropod bite Calciphylaxis Chronic lymphedema Crohn's disease Erythema Induratum (Nodular Vasculitis) Erythema nodosum Erythema nodosum-like Behcet disease Factitial panniculitis Infectious panniculitis Leukocytoclastic vasculitis Lipedema Lipodermatosclerosis Lupus panniculitis Lymphoma Necrobiosis lipoidica Postradiation pseudosclerodermatous panniculitis Pseudolymphoma Pyoderma gangrenosum Radiation dermatitis Rheumatoid nodule Ruptured cyst Scar Subcutaneous granuloma annulare Thrombophlebitis

INFLAMMATORY CELL TYPE	DISEASE
Numerous neutrophils	A1ATD Calciphylaxis Crohn's Erythema Induratum (Nodular Vasculitis) Erythema nodosum Erythema nodosum leprosum Factitial Infectious Pancreatic Pyoderma gangrenosum Rheumatoid arthritis Ruptured cyst Sweet's Thrombophlebitis Traumatic
Mostly lymphocytes	Connective tissue disease Dermatomyositis Eosinophilic fasciitis Erythema nodosum-like Behcet disease Lipedema Lipodermatosclerosis Lipoatrophy Lupus Lymphoma Necrobiosis lipoidica Postradiation Pseudolymphoma Scleroderma
Eosinophils in variable number	Adult lipophagic atrophic panniculitis Arthropod Atrophy Cholesterol emboli Cold panniculitis Cytophagic histiocyte panniculitis Eosinophilic fasciitis Erythema nodosum EN-like Behcet disease Hypereosinophilic syndrome Infectious Injection-associated Leukocytoclastic vasculitis Lipophagic panniculitis of childhood Lupus Lymphoma Necrobiosis lipoidica Polyarteritis nodosa Pseudolymphoma Rheumatoid nodules Ruptured cyst Sclerema neonatorum Scleroderma Subcutaneous granuloma annulare Well's syndrome
Lymphohistiocytic infiltrate	A1ATD Cold Connective tissue disease Cytophagic histiocytic panniculitis EN like Behcet's disease Lipodermatosclerosis Necrobiosis lipoidica Nodular vasculitis
Variable plasma cells	Acrodermatitis chronica atrophicans Adult lipophagic atrophic panniculitis Connective tissue disease Crohn's Cytophagic histiocytic panniculitis Dermatomyositis Eosinophilic fasciitis EN leprosum EN-like Behcet's Infectious Lipoatrophy Lipodermatosclerosis Lipophagic panniculitis of childhood Lupus Lymphoma Necrobiosis lipoidica Nodular vasculitis Persistent arthropod Postradiation Pseudolymphoma Radiation Rheumatoid nodule Scar Scleroderma
Predominance of granulomatous inflammation	EN Erythema Induratum (Nodular Vasculitis) Factitial Granuloma annulare Granulomatous mastitis Infection Nodular vasculitis Rheumatoid nodules Ruptured cyst Silicon granuloma Subcutaneous fat necrosi of newborn
Mixed inflammatory infiltrate with granulomas	Crohn's Erythema Induratum (Nodular Vasculitis) EN Factitial Cytophagic histiocytic panniculitis EN like Behcet's Granuloma annulare Infectious Injection associated Lymphoma Ruptured cyst Wegener granulomatosis
Mixed inflammatory infiltrate without granulomas	Arthropod Calciphylaxis Cytophagic histiocytic panniculitis Erythema Induratum (Nodular Vasculitis) EN EN leprosum Factitial Infectious Leukocytoclastic vasculitis Lipoatrophy Polyarteritis nodosa Pancreatic Ruptured cyst Sclerema neonatorum Subcutaneous fat necrosis of newborn Thrombophlebitis Traumatic

FINDING	DISEASE
Intracellular deposition of crystals	Factitial Gout Oxalosis Poststeroid Sclerema neonatorum Subcutaneous fat necrosis of the newborn
Often associated with hemorrhage and siderophages	A1ATD Arthropod Atheromatous emboli Calciphylaxis Cytophagic histiocytic panniculitis Erythema Induratum (Nodular Vasculitis) EN Factitial Infectious Ischemic fasciitis Leukocytoclastic vasculitis Lipodermatosclerosis Polyarteritis nodosa Povidone Radiation Sclerosing lipogranuloma Thrombophleblitis Traumatic
Extensive sclerodermiform changes	Acrodermatitis chronica atrophicans Drug injections Eosinophilic fasciitis Lipodermatosclerosis Lipoatrophy Lupus Necrobiosis lipoidica Paraneoplastic Postirradiation Radiation Scleroderma Sclerosing lipogranuloma
Deposition of mucin	Cold Granuloma annulare Ischemic fasciitis Lichen myxedematosus with subQ involvement Lipedema Lipoatropy Lupus
Focal with fatty tissue without inflammatory changes within same field	A1ATD Arthropod Cold Factitial Injection Polyarteritis nodosa Ruptured cyst
With calcification of subcutis	Calciphylaxis Dermatomyositis Facititial Lupus Necrobiosis lipoidica Oxalosis Pancreatic Scleroderma Sclerosing lipogranuloma Trauma
With calcification of blood vessels	Arteriosclerosis Calciphylaxis Diabetic microaniopathy Oxalosis Thromboangiitis obliterans
With lymphoid follicles	A1ATD Dermatomyositis Erythema Induratum (Nodular Vasculitis) EN Lupus Lymphoma Necrobiosis lipoidica Pseudolymphoma Scleroderma
With fasciitis	Brucellosis Drugs (L-tryptophan, phytonadione) Eosinophilic fasciitis GVH Ischemic fasciitis Lipodermatosclerosis Necrotizing fasciitis Paraneoplastic Scleroderma Toxic oil syndrome
With little inflammation	Calciphylaxis Chronic lymphedema Lipedema Lipodermatosclerosis Oxalosis Pancreatic Poststeroid Scar Sclerema neonatorum Trauma
Reduction in size of lipocytes	Lipoatrophy, primary vs. secondary
Simulators with atypical cells	Arthropod Cytophagic histiocytic panniculitis Ischemic Lipoatrophy Lymphoma Lipedema Radiation Ruptured cysts Sarcoma Silicone granuloma
Macrophages and/or erythrophagocytosis	Cytophagic histiocytic panniculitis Rosai-Dorfman disease Ruptured cyst Infectious
Fibrosis of dermis and subcutis	Chronic lymphedema Scar

NECROSIS	DISEASE
Pallor of adipocytes	Calciphylaxis Coma Coumarin necrosis Diabetic microangiopathy Embolic disease Erythema Induratum (Nodular Vasculitis) Infectious Leukocytoclastic vasculitis Lipodermatosclerosis Lymphoma Polyarteritis nodosa Severe arteriosclerosis Thromboangiitis obliterans
Pseudomembranes	Chronic arterial obstruction Cytophagic histiocytic panniculitis Dermatomyositis EN EN like Behcet's Factitial Infectious Lipodermatosclerosis Lupus Necrobiosis lipoidica Polyarteritis nodosa Rheumatoid arthritis Scleroderma Sclerosing lipogranuloma Thrombophlebitis Traumatic
Pseudocysts	Calciphylaxis Cold Erythema Induratum (Nodular Vasculitis) EN Factitial LCV Lipodermatosclerosis Postradiation Radiation Ruptured cyst Sclerosing lipogranuloma SubQ fat necrosis Trauma
Numerous lipophages	A1ATD Calciphylaxis Cold Erythema Induratum (Nodular Vasculitis) EN like Behcet's Factitial Lipodermatosclerosis Lipophagic panniculitis Lymphoma (angiocentric) Pancreatic Poststeroid Postradiation Sclerema neonatorum Sclerosing lipogranuloma SubQ fat necrosis Trauma
Hyaline material	Dermatomyositis Lipodermatosclerosis Lupus
Ghost cells without vasculitis	Pancreas Sclerema neonatorum Sclerosing lipogranuloma
Intensely basophilic material	Crohn's Factitial Infectious Pancreatic Pyoderma gangrenosum Ruptured cyst
Liquefactive changes	A1ATD Pancreas Rheumatoid arthritis
Necrotizing granulomas	Foreign body Erythema Induratum (Nodular Vasculitis) Infectious Sarcoidosis

CHANGE	DISEASE
Small blood vessels increased in number often showing thick walls	EN Infectious Lipoatrophy Lipodermatosclerosis Nodular vasculitis Rheumatoid nodules Subcutaneous granuloma annulare
Medium sized vessel vasculitis	Crohn's Erythema Induratum (Nodular Vasculitis) EN EN leprosum Infectious Lymphoma Polyarteritis nodosa Thromboangiitis obliterans Thrombophlebitis
Small vessel vasculitis	Dermatomyositis Erythema Induratum (Nodular Vasculitis) EN leprosum EN-like Behcet's Infectious LCV Lupus Necrobiosis lipoidica Polyarteritis nodosa Rheumatoid arthritis Thromboangiitis obliterans Wegener's granulomatosis

DISEASE ASSOCIATIONS	CHARACTERIZATION
GLATIRAMER ACETATE INJECTION
Localized panniculitis secondary to subcutaneous glatiramer acetate injections for the treatment of multiple sclerosis: a clinicopathologic and immunohistochemical study. Soares Almeida LM, Requena L, Kutzner H, Angulo J, de Sa J, Pignatelli J. Department of Dermatology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.	J Am Acad Dermatol. 2006 Dec;55(6):968-74. Epub 2006 Jun 21. Abstract quote BACKGROUND: Glatiramer acetate has been shown to be effective in reducing the relapse and improving the disability of patients with multiple sclerosis. The most common adverse effects at the injection sites include pain, inflammation, and induration that spontaneously disappear within hours or a few days. OBJECTIVE: We sought to characterize the histopathologic findings of localized panniculitis induced by glatiramer acetate at the injection sites. METHODS: Seven patients receiving daily glatiramer acetate injections for treatment of multiple sclerosis developed localized panniculitis at the injection sites. The lesions were histopathologically and immunohistochemically studied. RESULTS: The lesions consisted of a mostly lobular panniculitis, with lipophagic granuloma, namely histiocytes engulfing the lipids from necrotic adipocytes. In many areas, scattered neutrophils and eosinophils were seen both in the septa and in the fat lobules. Connective tissue septa showed widening and fibrosis in conjunction with many lymphoid follicles, presenting with germinal center formation. Immunohistochemically, the inflammatory infiltrate of the fat lobule consisted of CD68+ histiocytes and suppressor/cytotoxic T lymphocytes. In contrast, the lymphoid follicles in the septa and at the interface between septum and fat lobule were mainly composed of B lymphocytes. LIMITATIONS: Only one biopsy was performed in each patient and, therefore, it was not possible to study the histopathologic evolution of the panniculitic process. CONCLUSIONS: Localized panniculitis at the sites of subcutaneous injections of glatiramer acetate for treatment of multiple sclerosis seems to be a rare, but characteristic side effect of this therapy. The histopathologic pattern of these lesions consists of a mostly lobular panniculitis, with histiocytes and T lymphocytes in the fat lobule and thickened septa with scattered lymphoid follicles, which are mostly composed of B lymphocytes.
INTERFERON BETA INJECTIONS
Lobular panniculitis at the site of subcutaneous interferon beta injections for the treatment of multiple sclerosis can histologically mimic pancreatic panniculitis. A study of 12 cases. Ball NJ, Cowan BJ, Hashimoto SA. Department of Pathology, The University of Britsih Columbia and Vancouver General Hospital, Vancouver, British Columbia, Canada.	J Cutan Pathol. 2009 Mar;36(3):331-7. Abstract quote BACKGROUND: Thrombosis, mucinosis and necrosis are well-described complications of subcutaneous interferon beta injections. METHODS: We report 12 incisional biopsies from subcutaneous interferon beta injection sites in 12 multiple sclerosis (MS) patients from a single neurologist's practice. RESULTS: We identified abscesses (two cases) or induration (two cases) in acute clinical lesions and lipoatrophy (eight cases) in chronic lesions (biopsied over a year after symptom onset at injection sites). Biopsies from three acute lesions showed vascular thrombosis, dermal mucinosis, lobular neutrophilic panniculitis, necrosis, calcification and hemosiderin deposition (biopsied 2 weeks to 2 months after symptom onset). Two cases contained sterile abscesses. Five of the eight chronic cases presented as hard, indurated lipoatrophy with livedo reticularis. Their biopsies showed subcutaneous calcification and lipoatrophy. Biopsies from the early calcific suppurative and late calcific atrophic phases histologically resembled the early and late phases of subcutaneous saponification in pancreatic panniculitis. CONCLUSIONS: Reactions at the site of subcutaneous interferon beta injections are common. Lipoatrophy can be clinically identified in 39 of 85 MS patients (46%) receiving subcutaneous interferon beta injections for 1 year or longer in our practice. A reaction to interferon should be considered in the differential diagnosis of biopsies that show features of pancreatic panniculitis.

HISTOLOGICAL VARIANTS	CHARACTERIZATION
GENERAL
Panniculitis: clinical overlap and the significance of biopsy findings. Chopra R, Chhabra S, Thami GP, Punia RP. Laboratory, Histopathology Division, King Fahd Hospital, Hofuf, Al-hassa, Saudi Arabia.	J Cutan Pathol. 2009 Aug 25. Abstract quote Background: Panniculitides are well-recognized clinicopathologic entities but the non-specificity of their clinical and pathological features often troubles the diagnostician. Methods: This study retrospectively evaluates the clinical overlaps and the significance of histological findings among various panniculitides. Results: The clinical evaluation in 55 panniculitides cases suggested the diagnosis of typical erythema nodosum (EN) in 26 cases, atypical EN in 17 cases, atypical nodular vasculitis (NV) in two cases, soft tissue infection in five cases and five cases remained unclassified. Skin biopsy evaluation provided definite panniculitis diagnosis in 53 cases including EN (28 cases), leukocytoclastic vasculitis (seven cases), NV (four cases), superficial thrombophlebitis (ST) (two cases), eosinophillic panniculitis (EP) (three cases), infection-related panniculitis (five cases), and one case each of erythema nodosum leprosum (ENL), lupus panniculitis (LP), pancreatic fat necrosis and acne conglobata with two cases remaining unclassified. Histologically, 'predominantly septal' and 'mixed panniculitis' were the chief inflammatory patterns in EN cases, while mixed panniculitis was seen in most LCV cases and predominantly lobular and mixed panniculitis in NV cases. Conclusions: Biopsy evaluation of a panniculitis lesion is usually significant, and the application of a combination of histologic features rather than of a single biopsy finding or an inflammatory pattern is helpful in the diagnosis of panniculitis.
EDEMATOUS SCARRING VASCULITIC PANNICULITIS
Edematous, scarring vasculitic panniculitis: a new multisystemic disease with malignant potential. Ruiz-Maldonado R, Parrilla FM, Orozco-Covarrubias ML, Ridaura C, Tamayo Sanchez L, Duran McKinster C. Department of Pediatric Dermatology, National Institute of Pediatrics, Mexico City, Mexico.	J Am Acad Dermatol 1995 Jan;32(1):37-44 Abstract quote BACKGROUND: Hydroa vacciniforme (HV) is a disease of unknown origin characterized by erythema, vesicles, necrosis, and varicelliform scars in light-exposed skin. Systemic involvement is absent. A few patients have been reported with "severe HV" with systemic involvement, development of non-Hodgkin's lymphoma, and a poor prognosis. OBJECTIVE: Our purpose was to characterize and differentiate our patients' disease from HV. METHODS: We performed a retrospective clinicopathologic study of 14 children previously diagnosed as having "severe HV." RESULTS: The extension and severity of the cutaneous lesions, fever, wasting, failure to thrive, hepatosplenomegaly, vasculitis, panniculitis, and potential development of lymphoma are features that clearly differentiate edematous scarring vasculitic panniculitis from HV. CONCLUSION: Edematous scarring vasculitic panniculitis is a novel multisystemic disease with malignant potential that is not related to classic HV.
LIPODERMATO-SCLEROSIS
Morphology of lymphatics in human venous crural ulcers with lipodermatosclerosis. Eliska O, Eliskova M. Department of Anatomy, 1st Medical Faculty, Charles University Prague, Czech Republic.	Lymphology 2001 Sep;34(3):111-23 Abstract quote A morphological evaluation of lymphatic vessels of skin leg ulcers was performed in 39 human subjects with longstanding venous insufficiency and lipodermatosclerosis. Light and electron microscopy demonstrated that the superficial fibrin and inflammatory cell layers and intermediate blood capillary layer of the ulcer bed, which were primarily granulation tissue, did not contain lymphatics. Moreover, lymphatic capillaries were present only sporadically in the transition zone from granulation tissue to the deeper collagenous scar layer of the ulcer. In some instances, in the deepest part of the ulcer bed near the crural fascia, there were one or two thicker lymphatic collectors with valves, which were continuations of collectors from the plantar foot region. Lymphatics were present at the border of the ulcer and in lipodermatosclerotic skin, but the endothelium and muscle lining layer were partially destroyed. Lymphatic capillaries were characterized by open interendothelial junctions in conjunction with subendothelial edema. In lipodermatosclerotic skin, the morphologic changes suggest that absorption of interstitial fluid and lymph is markedly disturbed adjacent to the ulcer bed, which likely contributes to both slow healing and high recurrence of skin ulcers associated with longstanding venous insufficiency.
Lipodermatosclerosis: Review of cases evaluated at Mayo Clinic Alison J. Bruce, MBChBa Daniel D. Bennett, MDa Christine M. Lohse, BSb Thom W. Rooke, MDc Mark D. P. Davis, MB, MRCPIa Rochester, Minnesota Copyright	J Am Acad Dermatol 2002;46:187-92 Abstract quote Background: Lipodermatosclerosis describes bound-down, sclerotic skin involving the lower extremities. Objective: Our purpose was to describe the demographic and clinical features of patients with lipodermatosclerosis. Methods: This was a retrospective study of patients presenting to Mayo Clinic between 1976 and 1998 with a diagnosis of lipodermatosclerosis. Results: Of 97 patients, 84 (87%) were women. Mean age was 62 years (range, 25-88 years). Mean body mass index was 34.3 (range, 17.8-71.5). Clinical signs were bilateral involvement in 44 patients (45%), induration localized to a discrete plaque in 49 (51%), erythema in 69 (71%), hyperpigmentation in 57 (59%), ulceration in 13 (13%), concomitant edema in 69 (71%), and varicosities in 55 (57%). Vascular studies performed on 72 patients showed abnormalities in 49: deep venous incompetence in 33 (67%), calf muscle pump abnormality in 19 (39%), abnormal pulsatility in 10 (20%), and obstruction in 1 (2%). Conclusion: Lipodermatosclerosis was associated with female sex, middle age, high body mass index, and venous abnormalities.
POSTIRRADIATION PANNICULITIS
Postirradiation Pseudosclerodermatous Panniculitis Loreto Carrasco, M.D. Carmen Moreno, M.D.; Maria Antonia Pastor, M.D.; Maria Jos� Izquierdo, M.D; Carmen Fari�a, M.D.; Lucia Mart�n, M.D.; Omar P. Sang�eza, M.D.; Luis Requena, M.D. From the Departments of Dermatology (L.C.,A.P.,J.I., C.F.,L.M.,L.R.) and Pathology (C.M.), Fundaci�n Jim�nez D�az, Universidad Aut�noma, Madrid, Spain, and Departments of Dermatology and Pathology (O.P.S.), Wake Forest University, Winston Salem, North Carolina.	Am J Dermatopathol 2001;23:283-287 Abstract quote Pseudosclerodermatous panniculitis is an unusual variant of panniculitis that results as a complication of megavoltage radiotherapy. Four women developed this unusual entity on the anterior chest and abdominal skin after receiving megavoltage therapy for either breast carcinoma or painful bone metastases from breast carcinoma. Histopathologically, the epidermis and dermis of the involved area showed little or no evidence of radiodermatitis. The main findings were confined to the subcutaneous tissue and consisted of thickened, sclerotic septa composed of both thick and thin collagen bundles, and a lobular panniculitis characterized by lipophagic granulomas and scattered lymphocytes and plasma cells. Additionally, one of the cases showed markedly dilated vascular spaces with the appearance of lymphatics in the upper part of the dermis. Pseudosclerodermatous panniculitis after irradiation is an unusual cutaneous complication of megavoltage radiotherapy that should be distinguished from subcutaneous metastatic disease, cellulitis, or connective tissue diseases involving the subcutaneous fat. The differential diagnosis can be established on the basis of the characteristic histopathologic features of postirradiation pseudosclerodermatous panniculitis.
PSEUDO-MEMBRANOUS (LIPOMEMBRANOUS) PANNICULITIS
Lipomembranous (membranocystic) fat necrosis. Clinicopathologic correlation of 38 cases. Snow JL, Su WP. Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.	Am J Dermatopathol 1996 Apr;18(2):151-5 Abstract quote Clinicopathologic correlation of cutaneous biopsy specimens demonstrating typical lipomembranous fat necrosis was performed. Material from 732 biopsies of various subcutaneous inflammatory disorders seen at our institution in the past 5 years was screened for typical lipomembranous (membranocystic) changes in the panniculus, and 39 specimens from 38 patients with these changes were identified. The most common clinical context in which this condition was observed was in chronic sclerotic plaques of the lower legs associated with venous insufficiency (37% of the total cases). All patients were women, and the majority were obese. Typical lipomembranous fat necrosis was also observed in eight cases (21%) of erythema nodosum, three (8%) of morphea or subcutaneous morphea (or both), two (5%) of lupus panniculitis, two (5%) of necrobiosis lipoidica, and in single cases of polyarteritis nodosa, necrotizing vasculitis, and erysipelas. Six cases (16%) had no definite underlying disease. The mean age of all patients was 57 years (range 32-86 years), and 34 patients (89%) were women. Of the five major categories identified, lipomembranes lining macrocysts and microcysts were most prominent in the venous insufficiency- and morphea-related cases and were much less prominent in erythema nodosum, lupus panniculitis, and necrobiosis lipoidica, which generally showed histopathologic findings typical of these disorders. In addition to lining the macrocystic and microcystic cavities formed in the fat lobules, lipomembranes were prominent in areas of septal fibrosis in all cases associated with morphea and necrobiosis lipoidica and in 35% and 25% of venous insufficiency- and erythema nodosum-related cases, respectively. In lupus panniculitis, lipomembranes were most prominent in areas of hyaline necrosis. We conclude that lipomembranous fat necrosis is most likely a nonspecific form of ischemic fat degeneration that may be induced by various clinical entities. This change is most often seen in venous insufficiency-associated chronic sclerotic plaques typically observed in middle-aged obese women, and we propose the term stasis-associated lipomembranous panniculitis (SALP) to describe this most common form of lipomembranous fat necrosis.
Subcutaneous pseudomembranous fat necrosis: new observations Diaz-Cascajo C, Borghi S. Center for Dermatopathology, Freiburg, Germany.	J Cutan Pathol 2002 Jan;29(1):5-10 Abstract quote BACKGROUND: Pseudomembranous fat necrosis is a peculiar manifestation of necrosis of adipose tissue characterized by formation of pseudocystic cavities lined by crenulated membranes. The underlying mechanism for the formation of pseudomembranes is unknown and numerous hypotheses have been proposed. Despite divergent interpretations, most authors consider necrotic fat cells to be the anatomic substrate for the formation of pseudomembranes. METHODS: A total of 341 panniculitides were reviewed for the presence of pseudomembranous fat necrosis. The specific diagnoses were established after correlation of all available clinical and laboratory data with the histopathology. Special attention was given to the time in the evolution of the disease when the biopsy was taken. Additional immunohistochemical studies were performed in 12 cases. RESULTS: Thirty of 341 cases of different types of panniculitides were found to show pseudomembranous fat necrosis, namely: 10 of 15 cases of sclerosing panniculitis (lipodermatosclerosis), 6 of 95 cases of erythema nodosum, 7 of 34 cases of traumatic panniculitis, 1 of 7 cases of lupus panniculitis, 1 of 20 cases of erythema induratum Bazin (nodular vasculitis), 1 of 9 cases of necrobiosis lipoidica, 1 of 4 cases of sclerotic lipogranuloma, 1 of 9 cases of infectious panniculitis (erysipelas), 1 of 2 cases of pancreatic panniculitis, and 1 of 4 cases of subcutaneous sarcoidosis. Pseudomembranous fat necrosis labelled strongly for the histiocytic markers CD68 and lysozyme. CONCLUSIONS: Our series provides data suggesting that pseudomembranous fat necrosis represents a dynamic process that varies according to the evolution of the lesion at the time of the biopsy. In biopsies taken from early foci of panniculitides pseudomembranes show vescicular or picnotic nuclei. Later, pseudomembranes retain their crenulated appearance but lack nuclear elements. Furthermore, we present histopathologic, histochemical, and immunohistochemical evidence that pseudomembranous fat necrosis results from the interaction of residual products of disintegrated fat cells and macrophages. Histiocytic markers such as CD68 and lysozyme may be used as reliable tools in order to detect pseudomembranes in panniculitides.
SEPTAL PANNICULITIS
Mostly septal panniculitis Luis Requena, MD and Evaristo S�nchez Yus, MDb Madrid, Spain	J Am Acad Dermatol 2001;45:163-83 Abstract quote The panniculitides represent a group of heterogeneous inflammatory diseases that involve the subcutaneous fat. The specific diagnosis of these diseases requires histopathologic study because different panniculitides usually show the same clinical appearance, which consists of subcutaneous erythematous nodules on the lower extremities. However, the histopathologic study of panniculitis is difficult because of an inadequate clinicopathologic correlation, and the changing evolutionary nature of the lesions means that biopsy specimens are often taken from late-stage lesions, which results in nonspecific histopathologic findings. In addition, large-scalpel incisional biopsies are required. However, we believe that by obtaining appropriate biopsy specimens and with adequate clinicopathologic correlation, a specific diagnosis may be rendered in most cases of panniculitis. It must be accepted that all panniculitides are somewhat mixed because the inflammatory infiltrate involves both the septa and lobules; however, in general the differential diagnosis between a mostly septal and a mostly lobular panniculitis is straightforward at scanning magnification. Mostly septal panniculitides with vasculitis include leukocytoclastic vasculitis involving the small blood vessels of the septa; superficial thrombophlebitis resulting from inflammation and subsequent thrombosis of large veins of the septa; and cutaneous polyarteritis nodosa, which is a vasculitis involving arteries and arterioles of the septa of subcutaneous fat with few or no systemic manifestations. Often septal panniculitides with no vasculitis are the consequence of dermal inflammatory processes extending to the subcutaneous fat, such as necrobiosis lipoidica, scleroderma, subcutaneous granuloma annulare, rheumatoid nodule, and necrobiotic xanthogranuloma. However, in other cases, the inflammatory process is primarily located in the fibrous septa of the subcutis with or without involvement of the overlying dermis. The most frequently seen septal panniculitis is erythema nodosum, which, in fully developed lesions, is characterized histopathologically by Miescher's radial granulomas in the septa.