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subcutaneous panniculitis - like t - cell lymphoma ( sptcl ) is a very rare form of skin lymphoma that is localized primarily to the subcutaneous adipose tissue without palpable involvement of the lymph nodes .
it was first described in 1991 in an 8-case series   but was not recognized as a distinct entity by the world health organization until 2001 .
it is estimated that sptcl accounts for less than 1% of all non - hodgkins lymphomas .
most often it presents as multiple , painless , subcutaneous nodules on the extremities and trunk . in its early phases
, the nodules may resolve without treatment and subsequently new nodules may develop on the same or different skin locations .
diagnosis of sptcl is a challenge , especially during initial contact with physicians when symptoms mimic other , more common conditions , such as benign panniculitis , eczema , dermatitis , psoriasis , cellulites , and other skin and soft tissue infections .  
clinical and systemic symptoms are nonspecific and can include fever , chills , and weight loss ; approximately half of patients develop mild cytopenias .
more serious conditions associated with sptcl include hepatosplenomegaly , mucosal ulcers , serosal effusions , hemophagocytosis syndrome ( hps ) , and pancytopenia , though these are less common [ 3 , 4 ] .    here
we describe a case of a middle - aged woman who presented with recurring fevers of unknown origin and an 8-month history of thigh and leg swelling and rash .
after several in - patient and out - patient visits , she was diagnosed with sptcl based on clinical history and results of surgical pathology .
a 44-year - old morbidly obese female presented to the emergency department with fever of unknown origin ( 101.8f at admission ) and chills for 10 days that were unresponsive to antibiotics ( cephalexin ) .
she had a history of bulimia , depression , anemia , gastritis , hypertension , and rheumatic fever .
she also had chronic skin lesions on the left lower lateral thigh and left upper calf for eight months but reported increased pain in those areas with development of yellow discharge , light bleeding , and numbness over the past 10 days .
the rash showed multiple areas of activity and remission presenting as spreading rings ( figure 1 ) .
numerous visits to dermatologists , plastic surgeons , and infectious disease specialists resulted in multiple failed courses of oral antibiotics .
several skin lesion biopsies resulted in differential diagnoses of lichen simplex chronicus versus   panniculitis versus   prurigo nodularis .
a deep fascia biopsy one month prior was interpreted as granulomatous panniculitis with negative stains for acid - fast bacilli and fungi .   at admission ,
labs were within normal limits with the exception of low wbc ( 3.2  k / ul , normal = 4.810.8  k / ul ) and abnormal liver function tests ( lft ) ( bun = 6  mg / dl , n = 717  mg / dl ; alt = 79  u / l , n = 952  u / l ; ast = 85  u / l , n = 1436  u / l ; alkphos = 164  u / l , n = 37126 
there was progressive worsening of neutropenia ( wbc = 2.4  k / ul ) and lft ( bun = 4  mg / dl ; alt = 116  u / l ; ast = 146  u / l ; alkphos = 212  u / l ) . hepatitis b and c tests were negative .  
results of biopsy of left upper thigh showed interface / lichenoid dermatitis with granulomatous features and lobular fat necrosis . left lower leg biopsy showed similar , but more subtle , results . at this time ,
the pathologist differential diagnoses included collagen vascular disease ( e.g. , lupus erythematosus ) , foreign body reaction / unusual drug eruption , sarcoidosis , and kikuchi 's disease .
culture from biopsy grew pantoea agglomerans . due to clinical presentation and positive culture results ,
three months later , the patient was readmitted with periodic high fever , chills , nausea , night sweats , and vomiting .   
she continued to be neutropenic ( wbc = 2.9 ) with slightly elevated lft ( alt = 57  u / l ; ast = 57  u / l ; alkphos = 149  u / l ) .  
after excisional biopsy from the left lower leg and the left groin area , including a lymph node , she was discharged home on antibiotics .
surgical pathology for the left lower leg was consistent with mild perivascular small lymphocytic infiltrate without specificity . on low - power field , results for the left groin area sample showed extranodal fibroadipose tissue containing a lymphoid infiltrate with a pattern similar to lobular and septal panniculitis ( at 10x magnification ) ( figure 2(a ) ) . on high - power field ( figures 2(b)2(g ) ) , the lymphoid cells were markedly atypical with irregular nuclei .
there were numerous fat cells rimmed by atypical lymphoid cells as well as abundant single - cell necrosis .
the lymph node biopsy revealed a spectrum of small , medium , and some large cells .
immunohistochemical stains for the left groin area sample were positive for cd3 and cd8 but negative for cd4 and cd56 ( figure 2 ) .
the lymph node had preserved architecture , reactive germinal centers , and paracortical hyperplasia with a spectrum of small , medium , and some large cells ; there was no definite involvement by lymphoma . based on surgical pathology results , a diagnosis of sptcl involving extranodal
the surgical pathology results were most consistent with an sptcl phenotype referred to as tcr. the patient was referred to oncology and began chop ( i.e. , cyclophosphamide , adriamycin , vincristine , and prednisone ) therapy regimen .
patient was admitted 5 months later for complicated skin and skin structure infection ( csssi ) of the lower abdomen and mons pubis , right groin , and upper thigh , due to culture - proven mrsa .
the areas that had previously showed signs of sptcl were responding very favorably to chop therapy ( figure 3 ) .
there are two distinct types of sptcl , classified by the t - cell receptor ( tcr ) phenotype and immunophenotypic characteristics .
the first , tcr , is characterized by an indolent , protracted course and is usually cd4 , cd8 , and cd56 .
the second , tcr , is associated with rapid clinical deterioration and coexisting hemophagocytosis syndrome ( hps ) ; it is usually cd4 , cd8 , and cd56 .
currently , the medical community uses the sptcl designation for patients with tcr , whereas tcr is designated as cutaneous gamma / delta positive t - cell lymphoma ( c-tcr ) [ 4 , 6 ] .   for the purposes of the current report , sptcl is being used to denote the umbrella of patients with tcr or c-tcr , while the individual phenotypes are being used to describe the specific phenotypes .  
diagnosis of sptcl is based on pathological examination of skin and subcutaneous tissue , immunohistochemical staining patterns , molecular analysis , and clinical characteristics .
patients with sptcl present with nodules or plaques ; ulcerations may also develop , but this occurs in a significantly larger proportion of patients with the c-tcl phenotype ( 45% versus   6% in tcr ) .
b - symptoms ( e.g. , fever , night sweats , and weight loss ) and cytopenias are common in both phenotypes .
approximately 75% of patients with sptcl have multifocal cutaneous involvement . lesions typically develop on the arms , legs , and/or trunk .
previous to diagnosis of sptcl , the patient we report on had numerous visits to both in - patient units and out - patient clinics where benign panniculitis was the primary diagnosis , a common occurrence in cases of sptcl .  
as described and illustrated by parveen and thompson   and paulli and colleagues , sptcl is characterized histologically by neoplastic lymphoid cells infiltrating mainly the lobular areas of the subcutaneous tissue . in cases of c-tcl ,
lymphocytes exhibit slight atypical features , including hyperchromatic , angulated nuclei , and indistinct cell borders .
admixed benign histiocytes , plasma cells , and neutrophils are present , mimicking benign panniculitis .
scattered mitoses , apoptotic cells , karyorrhectic debris , focal areas of fat necrosis , and rimming of individual fat cells by neoplastic cells are also common in sptcl [ 911 ] .  
rimming of fat cells can be seen in primary and secondary cutaneous lymphomas and in lobular panniculitis .  
some cases of sptcl have features of vague granuloma formation , which is also present in granulomatous panniculitis .
vasculitis has been rarely reported ; angiocentricity and angiodestruction are not features of sptcl . as in our case , multiple
tcr cells are cd8 and usually cd30 and cd56 whereas c-tcl is usually cd8 , cd56 , and cd30 [ 3 , 4 , 13 ] .   in terms of differential diagnosis ,
benign panniculitis usually has aggregates of cd20 b - cells mixed with cd3 cells that are both cd4 and cd8 .
primary cutaneous cd56 natural killer - like t - cell lymphoma is both cd30 and cd56 , and unlike sptcl , is often positive for epstein - barr .   in our case ,
the left groin tissue sample exhibited classic immunophenotyping characteristics of tcr , including abnormal lymphoid cells from extranodal tissues that were cd3 , cd4 , cd8 , and cd56 .
one differential diagnosis that is of particular interest is pfeifer - weber - christian disease ( pwcd ) , which is a rare inflammatory disorder of the subcutaneous adipose tissue .
pwcd is characterized by recurrent subcutaneous inflammatory nodules paired with systemic symptoms , such as fever and malaise .
since pwcd is a diagnosis based on exclusion , and since it can present very similar to sptcl , it is generally thought that some , if not many , described cases of pwcd may indeed be sptcl . furthermore , since cyclosporine is an often - successful form of treatment for pwcd and for tcr , misidentification of the disease becomes more of a possibility .   imaging technology has begun to be utilized in the diagnostic process ; it is also being used for monitoring disease response to therapy .
positron emission tomography ( pet ) scanning may be useful for staging sptcl and also for monitoring treatment responses while a patient is undergoing chemotherapy .
whole body mri is also appropriate for assessing the extent of disease and examining response to treatment .
as described by go and wester , lesions due to tcr initially respond well to treatment with steroids , but more than 70% of responders achieve only short remission periods .
exclusive treatment with radiotherapy in cases of localized skin lesions is highly effective , with reported partial or full response rates of around 80% .
chop - like therapies are the most commonly used initial types of chemotherapy , with overall complete or partial remission rates of 50% .
few cases have reported use of intensive chemotherapy ( e.g. ,   promace - cytabom , macop - b ) or fludarabine - based chemotherapies as initial treatments , although these have been relatively effective with overall remission rates of more than 70% .
numerous types of salvage therapies have been used , though rarely , including all , mini - beam , and eshap . when implemented
high dose chemotherapy is the most effective treatment with more than 90% remission , but is very rarely used . in some cases , autologous bone marrow transplants and stem cell transplants
biologic agents , such as interferon- , have been used for a limited number of cases without strong evidence of effectiveness .
treatment of aggressive cases of sptcl with anthracycline - containing chemotherapy has generally had poor outcomes
. there has been one report of successful use of purine analog fludarabine in combination with mitoxantrone and dexamethasone ( fnd ) for treating a multifocal and aggressive cd8 sptcl ; the patient achieved complete remission after one course of treatment and , after a total of six courses , remained in remission for more than 3 years . additionally , a case of sptcl with hps that was resistant to chop therapy
was reported to achieve complete remission ( with 3-year followup ) after combination chemotherapy using the bfm-90 protocol .
the presence of hps , however , significantly decreases survival rates ; the five - year survival rates for tcr without hps are around 90% , whereas if hps is present the rate falls to less than 50% . on the other hand ,
there is rapid clinical deterioration in c-tcl whether hps is present or not , with a 5-year survival rate of less than 20% in either group [ 3 , 4 ] . even without treatment , metastasis of tcr sptcl is very rare .
metastasis is more common in c-tcl , and metastatic sites have included the lungs , liver , kidneys , cns , and oral mucosa .  
when a patient presents with a long history of panniculitis - like lesions that have been unresponsive to topical and antibiotic therapy and are accompanied by nonspecific clinical symptoms , sptcl should be considered .  
biopsy with a sample deep enough to include subcutaneous tissue is essential ; additionally , high power fields to analyze samples should be used in order to make an accurate differential diagnosis .
immunochemistry should be completed since it is the best way to differentiate between sptcl and other , more common diagnoses , as well as to guide treatment decisions .
delayed diagnosis can lead to worsening of symptoms and higher probability of morbidity , such as severe skin infections .
subcutaneous panniculitis - like t - cell lymphoma ( sptcl ) is a very rare form of skin lymphoma that is localized primarily to the subcutaneous adipose tissue without palpable involvement of the lymph nodes . 
 diagnosis of sptcl is a challenge , especially during its early phases when symptoms mimic other , more common conditions , such as benign panniculitis , eczema , dermatitis , psoriasis and cellulitis . 
 clinical and systemic features are nonspecific and can include fever , chills , and weight loss . further complicating diagnosis is the high number of false negatives provided by biopsy . here 
 we present a case of sptcl that illustrates the full course of the disease , from presentation and multiple misdiagnoses to correct disease recognition and successful treatment . 
 a review of the challenges of diagnosis is provided with recommendations for more accurate and timely recognition of sptcl .