Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis

doi:10.4236/mps.2012.24024

Paper Menu >>

Journal Menu >>

Modern Plastic Surgery, 2012, 2, 99-102

http://dx.doi.org/10.4236/mps.2012.24024 Published Online October 2012 (http://www.SciRP.org/journal/mps) 99

Primary Cutaneous Diffuse Large B-Cell Lymphoma

(Leg Type) Presenting as Necrotising Fasciitis

Niall M. McInerney*, Kieran T. Power, Alan J. Hussey

Department of Plastic and Reconstructive Surgery, Galway University Hopsital, Galway, Ireland.

Email: *[email protected]

Received April 27th, 2012; revised May 25th, 2012; accepted June 21st, 2012

ABSTRACT

Necrotising fasciitis is a rare rapidly progressive, life threatening, soft tissue infection which spreads along fascial

planes. We present a patient who was diagnosed with a primary cutaneous Diffuse Large B-Cell Lymphoma (leg type)

following initial presentation as probable necrotising fasciitis. Presentation was of a painful swollen leg, septic shock

and MRI findings consistent with the clinical sig ns. Diagnosis of ne crotisin g fasciitis remains ch allen ging and it is o ften

missed in the early stages. Early fascial biopsy and histopathological analysis is useful in cases where the diagnosis is

unclear. We feel that this case highlights these important issues and will benefit others in their management of similar

cases in the future.

Keywords: Cutaneous; Lymphoma; Necrotising; Fasciitis

1. Introduction

Necrotising fasciitis is a rare rapidly progressive, life

threatening, soft tissue infection which spreads along

fascial planes [1]. If left untreated it is invariably fatal. A

high index of clinical suspicion is therefore warranted.

There has been a 5-fold increase in incidence over the

past decade, with increasing age being an important risk

factor [2]. It can be caused by group A Streptococcal

infection often incombinatio n with Staphlococcus Aureu s.

It may also be polymicrobial with several aerobic and

anaerobic organisms implicated, including Bacteroides,

Clostridium, Pep tostrep tococcus , Enterobacteriaceae, co-

liforms, Proteus, Pseudomonas, and Klebsiella. Presen-

tation can occur anywhere in the body but the lower limb

is most commonly affected, varying from 32% - 58%

[3,4]. Diagnosis remains challenging and it is often

missed in the early stages. Early fascial biopsy and his-

topathological analysis is useful in cases where the diag-

nosis is unclear. Magnetic Resonanace Imaging (MRI)

may also be useful as it can differentiate between necro-

tising fasciitis and cellulites [5 ].

2. Case Report

A 82-year-old male who was referred a local district gen-

eral hospital with a two week history of pain, redness,

swelling and bruising of his left medial thigh; (Figure 1).

He had failed to respond to standard intravenous antibi-

otic therapy for a presumed diagnosis of cellulitis. Upon

presentation the thigh was very swollen and tense. There

was no ulceration or other skin lesion noted.

Clinically he was in septic shock. His inflammatory

markers were noted to be elevated (WCC 13.3, CRP 202),

with a deteriorating renal function and markedly elevated

lactate levels. Blood gas analysis showed a metaboloic

acidosis. The patient was transferred to the intensive care

unit (ICU) and commenced on intravenous Clindamycin,

Ciprofloxacin and Vancomycin. Tissue for culture failed

to isolate any organism.

MRI scan on the day of admission demonstrated skin

and subcutaneous thickening with oedema of the poste-

rior compartment crossing the fascial planes to the ante-

rior compartment (Figure 1). The muscles of the medial

compartment of the upper leg were preserved but grossly

oedematous (Figure 2). These findings in conjunction

with the history were highly suggestive of a severe in-

flammatory process.

After resuscitation the patient underwent urgent surgi-

cal debridement under general anaesthesia. The intraop-

erative findings revealed overlying necrotic skin and fas-

cia in the medial compartment of the thigh. There was

thrombosis of cutaneous vessels. The underlying muscles

were necrotic and there was extensive, purulent appear-

ing exudate. Samples were sent for histology and micro-

biology. A presumptive diagnosis of necrotising fasciitis

was made.

The patient was returned to ICU where he continued to

*Corresponding a uthor.

Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis

100

Figure 1. Axial MRI image of left thigh showing gross oe-

dema of the posterior compartment crosssing the fascial

planes into the anterior compartment.

Figure 2. Saggital MRI image of the left thigh showing skin

thickening of the left medial thigh with adductor oede ma.

be administered with intravenous antibiotics. He also

required haemodialysis and inotropic support. Further

debridements were undertaken on the third and fifth day.

A negative pressure dressing was applied. Although there

was no clinical evidence of infection, haematological

indices including CRP (325), WBC (21.4) and lactate

dehydrogenase (22 (normal 0.05 - 2.20)) continued to

deteriorate. A Computed Tomography (CT) scan of tho-

rax, abdomen and pelvis showed no other occult sepsis.

On day 15 the wounds were covered with split thickness

skin graft (Figure 3).

A diagnosis of primary cutaneous large B-cell lym-

(a) (b)

(c)

Figure 3. (a) Day 2 wound debridement: wound internally

packed with bethadine soaked gauze. (b), (c) Day 14 wound

debridement and split thickness skin grafting. Note a clean

wound with healthy skin edges and significant amount of

muscle resected. Note the extension of the lymphoma over

the patella.

phoma of the leg (PCLBCL-leg) was made after histo-

logical analysis of the fascia and attached adipose tissue

showed diffuse infiltration by atypical lymphoid cells

(Figure 4). The proliferation of lymphoid cells shows

so-called starry-sky appearance with the pres ence of large

histiocytes phagocyting nuclear debris. Mitotic figures

were also present. The atypical lymphoid cells showed

CD20 and BCL6 positivity.

He was referred to the haematology service, but he

continued to deteriorate in ITU and died before chemo-

therapy was commenced.

3. Discussion

Necrotising fasciitis typically presents with early signs of

hot overlying skin, intense erythema, small serous bullae,

and firm induration signifying underlying fascial in-

volvement but may appear as mild cellulites [6]. Connec-

tive tissue and fat is broken down by hyaluronidase and

lipases released by bacteria which allows rapid spread of

infection along fascial planes. Aggressive debridement is

the fundamental principle in the treatment of necrotising

Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis 101

(a) (b)

(c)

Figure 4. (a) Adipose tissue shows diffuse infiltraion by

lymphoid cells (×10); (b) Atypical lymphoblasts and im-

munoblasts predominate the picture with several mitotic

figures and apoptotic bodies (×40); (c) CD20 immunohisto-

chemistry shows strong positivity confirming B-cell origin

of the lesion.

fasciitis [7]. The va lue of obtaining a fresh frozen b iopsy

is evident not only in terms of improved diagnosis but

also survival [8,9].

Various B-cell lymphomas can present primarily in the

skin without evidence of extracutaneous disease [10].

Primary cutaneous large B-cell lymphomas [PCLBCLs] are

responsible for the majority of these [11]. These lypm-

homas are divided into three main subtypes; primary cu-

taneous marginal zone B-cell lymphoma (PCMZL), pri-

mary cutaneous follicle center-cell lymphomas (PCFCCLs)

and primary cutaneous large B-cell lymphoma of the leg

(PCLBCL-leg). PCLBCL-leg differs by being rapidly

progressive, having a poorer prognosis, higher age of

onset, and expressing bcl-2 protein in the vast majority of

cases [10,12]. The neoplastic B cells also express the

B-cell-associated antigen CD20. PCLBCL-leg develop

extracutaneous disease more frequently and patients have

a 5-year survival of 52% compared with 94% with

PCFCCL [13].

PCLPBL commonly presents with one or both legs

exhibiting a rapidly growing red or bluish tumour (Is it

cutaneous or subcutaneous?). An elevated serum lactate

deydrogenase has been identified in 11.7% of cases [14].

Approximately 25% of patients will develop extracuta-

neous disease at a mean time of 22 months while rarely

lesions may present in a primary location other than the

leg and carry a better prognosis [13,15].

Radiotherapy, chemotherapy and immunotherapy are

the mainstays of treatment [17]. Regimens typically in-

clude an anti-CD20 antibody (rituximab) in comination

with the antracycline based chemotherapy regimen

CHOP (r-CHOP) [15,17,18]. Radiotherapy may also be

considered particularly in presentations of a solitary

small skin tumour. Relapse rates following radiation

have been reported as 58% with extracutaneous progres-

sion rates of 30% [17]. Surgical excision is highly effec-

tive in PCMZL and PCFCCL with a similar efficacy to

radiotherapy, however its efficacy is not well described

in PCLPBL [19].

This case highlights the need for urgent tissue diagno-

sis even when you think the diag nosis is obvio us. Had an

earlier tissue diagnosis been made Initial treatment of

this patient with radiation and/or r-CHOP may have im-

proved his prognosis. The presence of a raised lactate

should also lead one to suspect cutaneous lymphoma. We

therefore recommend that urgent tissue biopsy be per-

formed in all cases of presumed necrotising fasciitis.

REFERENCES

[1] E. J. Whallett, J. H. Stevenson and A. D. Wilmshurst,

“Necrotising Fasciitis of the Extremity,” Journal of Plas-

tic, Reconstructive & Aesthetic Surgery, Vol. 63, No. 5,

2010, pp. e469-e473. doi:10.1016/j.bjps.2009.09.011

[2] R. Kaul, A. McGeer, D. E. Low, et al., “Population-

Based Surveillance for Group a Streptococcal Necrotizing

Fasciitis: Clinical Features, Prognostic Indicators, and

Microbiologic Analysis of Seventy-Seven Cases. Ontario

Group A Streptococcal Study,” American Journal of Me-

dicine, Vol. 103, No. 1, 1997, pp. 18-24.

doi:10.1016/S0002-9343(97)00160-5

[3] D. A. Anaya and E. P. Dellinger, “Necrotizing Soft-Tis-

sue Infection: Diagnosis and Management,” Clinical In-

fectious Diseases, Vol. 44, No. 5, 2007, pp. 705-710.

doi:10.1086/511638

[4] B. J. Childers, L. D. Potyondy, R. Nachreiner, et al., “Ne-

crotizing Fasciitis: A Fourteen-Year Retrospective Study

of 163 Consecutive Patients,” The American Journal of

Surgery, Vol. 68, No. 2, 2002, pp. 109-116.

[5] A. Rahmouni, O. Chosidow, D. Mathieu, et al., “MR

Imaging in Acute Infectious Cellulites,” Radiology, Vol.

192, No. 2, 1994, pp. 493-496.

[6] J. D. Urschel, “Necrotiz ing Soft Tissue Infections,” Post-

graduate Medical Journal, Vol. 75, No. 889, 1999, pp.

645-649. doi:10.1136/pgmj.75.889.645

[7] C. H. Wong, A. K. Yam, A. B. Tan, et al., “Approach to

Debridement in Necrotizing Fasciitis,” The American

Journal of Surgery, Vol. 196, No. 3, 2008, pp. e19-e24.

Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis

102

doi:10.1016/j.amjsurg.2007.08.076

[8] I. Stamenkovic and P. D. Lew, “Early Recognition of

Potentially Fatal Necrotizing Fasciitis. The Use of Fro-

zen-Section Biopsy,” The New England Journal of Medi-

cine, Vol. 310, No. 26, 1984, pp. 1689-1693.

doi:10.1056/NEJM198406283102601

[9] J. Majeski and E. Majeski, “Necrotizing Fasciitis: Im-

proved Survival with Early Recognition by Tissue Biopsy

and Aggressive Surgical Treatment,” Southern Medical

Journal, Vol. 90, No. 11, 1997, pp. 1065-1068.

doi:10.1097/00007611-199711000-00001

[10] R. Willemze, H. Kerl, W. Sterry, et al., “EORTC Classi-

fication for Primary Cutaneous Lymphomas: A Proposal

from the Cutaneous Lymphoma Study Group of the

European Organization for Research and Treatment of

Cancer,” Blood, Vol. 90, No. 1, 1997, pp. 354-371.

[11] P. Isaacson and A. Norton, “Cutaneous Lymphomas,” In:

P. G. Isaacson and N. A. Wright, Eds., Extranodal Lym-

phomas, Churchill Livingstone, London, 1994, p. 172.

[12] F. A. Geelen, M. H. Vermeer, C. J. Meijer, et al., “Bcl-2

Protein Expression in Primary Cutaneous Large B-Cell

Lymphoma is Site-Related,” Journal of Clinical Oncol-

ogy, Vol. 16, No. 6, 1998, pp. 2080-2085.

[13] F. Grange, M. W. Bekkenk, J. Wechsler, et al., “Prognos-

tic Factors in Primary Cutaneous Large B-Cell Lympho-

mas: A European Multicenter Study,” Journal of Clinical

Oncology, Vol. 19, No. 16, 2001, pp. 3602-3610.

[14] F. Grange, M. Beylot-Barry, P. Courville, et al., “Primary

Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type:

Clinicopathologic Features and Prognostic Analysis in 60

Cases,” Archives of Dermatology, Vol. 143, No. 9, 2007,

pp. 1144-1150. doi:10.1001/archderm.143.9.1144

[15] R. Willemze, E. S. Jaffe, G. Burg, et al., “WHO-EORTC

Classification for Cutaneous Lymphomas,” Blood, Vol.

105, No. 10, 2005, pp. 3768-3785.

doi:10.1182/blood-2004-09-3502

[16] P. L. Zinzani, P. Quaglino, N. Pimpinelli, et al., “Prog-

nostic Factors in Primary Cutaneous B-Cell Lymphoma:

the Italian Study Group for Cutaneous Lymphomas,”

Journal of Clinical Oncology, Vol. 24, No. 9, 2006, pp.

1376-1382. doi:10.1200/JCO.2005.03.6285

[17] N. J. Senff, E. M. Noordijk, Y. H. Kim, et al., “European

Organization for Research and Treatment of Cancer and

International Society for Cutaneous Lymphoma Consen-

sus Recommendations for the Management of Cutaneous

B-Cell Lymphomas,” Blood, Vol. 112, No. 5, 2008, pp.

1600-1609. doi:10.1182/blood-2008-04-152850

[18] B. Dreno, “Standard and New Treatments in Cutaneous

B-Cell Lymphomas,” Journal of Cutaneous Pathology,

Vol. 33, No. S1, 2006, pp. 47-51.

doi:10.1111/j.0303-6987.2006.00544.x

[19] P. Golling, A. Cozzio, R. Dummer, et al., “Primary Cu-

taneous B-Cell Lymphomas—Clinicopathological, Prog-

nostic and Therapeutic Characterisation of 54 Cases ac-

cording to the WHO-EORTC Classification and the

ISCL/EORTC TNM Classification System for Primary

Cutaneous Lymphomas Other than Mycosis Fungoides

and Sezary Syndrome,” Leuk Lymphoma, Vol. 49, No. 6,

2008, pp. 1094-1103. doi:10.1080/10428190802064925