Transcript Slides for residents

Dr F.Iraji
Case 1
 An 84 year old white male with newly diagnosed
basaloid squamous cell carcinoma of the right
mandibular gingiva was referred to our clinic by
otolaryngology for 6-12 month history of right sided
facial induration and erythema. The patient denied
any pain or pruritus, but endorsed a sensation of
tightness of the right face. He had no prior history of
radiation therapy.
Clinical History
 On physical exam, the right side of his face was faintly
erythematous, with firm woody induration extending
from temple to jaw line and just medial to the
nasolabial fold. A sclerotic focus was noted centrally
on the right cheek. Asymmetry was observed between
the right and left face, most prominent infraorbitally
and at the nasolabial fold. Assessment of cranial
nerve VII was unremarkable. A tissue biopsy was
performed.
Histopathology
 revealed an abundance of vascular channels in the
dermis that stained positive for CD31 (endothelial cell
marker), lymphatic vessel endothelial hyaluronan
receptor-1 (LYVE 1), and D2-40 (lymphatic endothelial
cell marker); and negative for human herpes virus 8
(HHV 8). Ten percent of the endothelial cells stained
positive for Ki67. No squamous cell carcinoma was
identified.
Cutaneous angiosarcoma
 Clinical presentation and histopathology:
Angiosarcoma is a rare high-grade malignant tumor
derived from vascular and lymphoid endothelium.
Cutaneous angiosarcoma is most often reported on the face
and scalp in elderly patients, or in association with chronic
lymphedema or prior radiation. Over 50% of cutaneous
angiosarcomas are located on the head and neck,
 Early disease is usually benign-appearing, often described
as bruise-like and poorly defined. As lesions progress,
induration, nodularity, edema, bleeding, and ulceration
may occur. The variable and subtle clinical findings
contribute to later patient presentation and diagnosis, by
which time patients may develop advanced disease.
Histology
 reveals atypical endothelial cells lining anastomosing
and infiltrative vascular spaces in the dermis. Cellular
pleomorphism and mitoses are variable, and less welldifferentiated patterns with poorly-formed vascular
channels or sheets of endothelial cells are commonly
encountered. Cells express positivity with CD31, CD34,
von Willebrand factor, Ulex europaeus 1 agglutinin,
and vascular endothelial growth factor (VEGF)
immunohistochemical stains, but not HHV 8.
Prognosis
 Cutaneous angiosarcoma is an aggressive tumor with
several factors contributing to an overall poor prognosis.
There is a high rate of disease recurrence, related in part to
delays in initial diagnosis, prevalence of multifocal disease,
and difficulty defining clinical and surgical margins.
Metastatic rate is also high, with early metastases to the
lung and pleural cavity, lymph nodes, liver, bone, and other
soft-tissues. Despite aggressive treatment with surgical
excision plus adjuvant radiation, local recurrence and/or
metastases are found in most patients.
.
Prognosis
 Specific factors impacting survival have been debated in
the literature. Many studies agree that large tumor size
(greater than 5 cm) is the most consistent indicator of
poorer prognosis. Other studies argue that histologic
grade, including epithelioid morphology, mitoses,
necrosis, and depth of invasion, is a more significant
predictor of survival. Anatomic site, older age of patient,
medical co-morbidities, and presence of metastases at
presentation may also impact survival, though the
significance of these factors is unclear. Most patients
succumb to the disease within 2 years of diagnosis. The 5
year survival rate for cutaneous angiosarcoma is 10-35%,
compared with 50-60% for other soft-tissue sarcomas
Treatment
 Treatment of cutaneous angiosarcoma is difficult, with
most recommendations evolving from case series.
Tumors may be multifocal, extend well beyond clinical
margins, and have satellite lesions that complicate
therapy. For local disease, wide surgical resection of
the primary cutaneous lesion, as well as utilization of
frozen tissue sections to define clear margins is
employed. Unfortunately, due to the nature of the
tumor, margins are often positive despite extensive
surgical resection, and patients may need repeated
surgeries for remaining disease
Treatment
 . Regardless, studies have demonstrated a high
percentage of patients with residual sarcoma following
numerous resections. Wide surgical excision is
especially complicated on the head and neck, and
post-operatively, patients risk significant mutilation,
with functional and cosmetic sequelae. Cure is rare
with surgery alone; for this reason, radiation with wide
treatment field is utilized as adjuvant therapy
following excision for local disease
control. Radiation as monotherapy is not curative,
but may be used as palliation for extensive nonresectable disease.
Treatment
 Adjuvant chemotherapy following surgery and radiation
has been described with mixed results. Neoadjuvant
chemotherapy may be employed to reduce the size of the
primary tumor in an attempt to improve cosmetic and
functional outcomes following surgery, however studies
have demonstrated recurrence rates of over 50%, and
suggest that neoadjuvant therapy does not significantly
affect survival or recurrence rates. It is not clear if
chemotherapy for metastatic disease improves overall
survival; its use is limited by patient co-morbidities and
toxicity. VEGF monoclonal antibodies (bevacizumab)
and tyrosine kinase inhibitors (sorafenib) have been
studied in trials for the treatment of cutaneous
angiosarcoma with promising results.
Case 2
 A 67-year-old caucasian man with no medical
problems presented with multiple sores on his
bilateral lower extremities and few on trunk, arms and
genitalia Patient denies fever, chills, night sweats
fatigue weight loss, hemoptysis, hematuria,
hematochezia, abdominal pain. Patient denies
history of inflammatory bowel disease or
malignancy. Patient denies any recent travel or new
medications.
Physical Exam
 The patient's lower extremities had multiple ulcers
with erythematous raised borders, few with satellite
pustules and multiple erythematous, indurated
plaques with central ulcerations, + odor.
The glans penis had ulcerative, erythematous plaques
resembling a balanitis.
The upper extremities had violaceous, indurated
plaques with central crusting.
Case 2
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Laboratory Data
CBC, LFTs, BUN/Cr, SPEP, ANA, RF, ANCA, ESR, CRP-normal
Imaging
CT of chest/abdomen/pelvis with and without contrast-normal
Microbiology
No fungus or mycobacterium isolated.
Histopathology
Punch biopsy specimen revealed ulcer with a heavy underlying
neutrophilic and granulomatous infiltrate. Deep dermis with
fibrosis, lobular proliferation of capillaries. Special stains (PAS,
GMS, Fite, Afb, Gram) negative.
Pyoderma gangrenosum (PG)
 has been described in association with a wide variety of
disorders, including Crohn’s disease, arthritis, rheumatologic
and hematologic conditions, HIV infection, sarcoidosis,
hereditary hypogammaglobulinemia, iatrogenic immune
suppression, malignancy. Pathogenesis is unknown, but
autoimmune mechanisms including immune complex-mediated
neutrophilic vascular reactions have been suggested. The
differential diagnosis includes Wegener’s granulomatosis,
polyarteritis nodosa, lymphoma, sporotrichosis and
antiphospholipid syndrome.Â
  PG is a global disease. It most commonly affects women
between 20 and 50 years of age. Fifty percent of patients have an
underlying systemic disease. Approximately 4% of cases of PG
occur in infants and children.
Pyoderma gangrenosum (PG)
 Major clinical forms of PG include bullous, pustular,
superficial, granulomatous and ulcerative and, in our case,
disseminated. The initial lesion is frequently a pustule on
an erythematous to violaceous base, an erythematous
nodule or a bulla. The characteristic lesion is an ulcer
with a necrotic undermined border. The base can be
purulent or vegetative.Â
 Skin biopsy specimens typically reveal necrosis, ulceration,
and abscess formation with a dense neutrophilic infiltrate.
 The differential diagnosis depends on the form and stage
of the disease. Broad categories include infection,
lymphoma, panniculitis, vasculitis, Sweet’s syndrome,
Behcet’s disease, malignancy.
Treatment
 First line therapy for disseminated disease is systemic
corticosteroids or cyclosporine or a combination of the
two. Experimental therapies include thalidomide,
mycophenolate mofetil, tacrolimus, dapsone,
azathioprine, infliximab, intravenous
immunoglobulins, granulocyte and monocyte
adsorption apheresis, plasmapheresis,
cyclophosphamide
Case 3
 32 year old white female at 25 weeks of gestation presents
with itchy rash on abdomen and lower extremities for 1
month. She complains of intense pruritus. She has similar
but milder rash in two previous pregnancies. At that time,
she was diagnosed as eczema and rash was controlled with
triamcinolone cream. Â The patient has no other known
medical issues.Â
 Physical exam
 Erythematous edematous patches and plaques on the
abdomen and erythematous patch with irregular border in
left lower extremity were found. Erythematous round
papules with hemorrhagic crusts were scattered in lower
extremities.
Histopathology
 Histology (H&E) showed interface dermatitis with
numerous eosinophils (see figure 3-5). DIF shows
linear deposits of C3 at the dermoepidermal junction.
Pemphigoid gestationis
 Pemphigoid gestationis is a rare vesiculobullous disease of pregnancy
and the most important to exclude.1 Pemphigoid gestationis is also
called gestational pemphigoid or herpes gestationis. It is intensely
pruritic and develops in late pregnancy or immediate postpartum
period. The incidence of the disease is estimated 1 in 50,000 in North
America, 1 in 40,000 in the UK. The disease is distributed worldwide.
 Pemphigoid gestationis usually presents during the second (34% of
patients) or third trimester (34% of patients) of pregnancy although
the onset could occur during the first trimester (18% of patients) and
during the postpartum period (14%).2 The abrupt onset of intensely
pruritic urticarial lesions are typically located on the abdomen, in 50%
of cases almost always involve the umbilicus. 3This could rapidly
progresses to a generalized pemphigoid-like eruption. But the face,
mucous membranes, palms and soles are usually spared. Although the
clinical presentation and course may be variable, it generally improves
in the third trimester and flare at the time of delivery (in 50-75% of
patients).
Pemphigoid gestationis
 Most disease spontaneously remits over weeks to months
after delivery without treatment. The disease could recur
with oral contraceptives usage and menstruation. Patients
with a history of pemphigoid gestationis seems to be at
increased risk for the subsequent development of Graves
disease.4 Newborns can develop urticarial-like or vesicular
skin lesions due to the passive transfer of IgG1 antibodies
from the mother to the fetus. These skin lesions resolve
within days to weeks as the antibodies are slowly
catabolized. Additionally, there is an increased risk of
prematurity and small-for-gestational-age neonates. No
increased fetal morbidity or mortality has been reported.5
Pathophysiology
 The pathogenically relevant auto-antigen has been identified as a
180 kDa transmembrane hemidesmosomal protein (BPAG2).
This protein has N-terminal end which is embedded within the
intracellular component of the hemidesmosome and C-terminal
end extracellularly. The extracellular section contains a series of
collagenous components interspersed by non-collagenous (NC)
domains. The reactivity of the autoantibodies is directed against
the N-terminal 45 amino acids of the 16th non-collagenous
domain (NC16A), which is located next to the cell membrane.
The autoantibodies (The anti-BPAG2) antibodies are IgG1
subclass and fix complement via the classical complement
pathway in the skin. Consecutively chemoattraction of
eosinophils and degranulation follows, resulting in tissue
damage and blister formation.1Â
Diagnosis and Treatments
 The most important and useful tools to confirm a
clinical diagnosis of pemphigoid gestationis are
histopathologic tests: subepidermal vesicle and a
perivascular infiltrate of lymphocytes and eosinophils
along the dermal-epidermal junction. The gold
standard of a diagnosis of the disease is the finding of
C3 with or without IgG in a linear band along the
dermal-epidermal junction. In salt-split skin
specimens, antibody deposition is located along the
bottom of the epidermal fragment.
Diagnosis and Treatments
 Due to rarity of the disease, there are no therapeutic
trials. In mild disease, potent topical corticosteroids,
emollients with antihistamines could be used although
there is general consensus of ineffectiveness of topical
steroid and antihistamines. Systemic corticosteroids
could be used for blistering disease (0.5-1mg/kg/day
prednisone) until a good clinical response is achieved.
Then prednisone can be tapered and maintained at
the lowest effective dose.
Case 4
 A full term 1 day old white male from an uncomplicated
pregnancy in a healthy mother was transferred to the
neonatal intensive care unit for vesicles, blisters and
desquamation of the hands and feet present at birth. The
mother denied a history of herpes simplex virus and there
was no family history of any blistering disorders.
 The infant was otherwise healthy appearing and showed no
signs of extramucocutaneous disease. Over the next several
days, the patient began to develop additional blisters in
areas of friction and minimal trauma including oral
mucosa.
Case 4
 An attempt was made to induce microvesicles on an area of
normal appearing skin on the chest. This area was immediately
biopsied for H&E as well as by electron microscopy.
Unfortunately, the H&E did not contain microvesicles and was
notable only for occasional vesicles within cells of the basal layer.
Electron microscopy also did not contain microvesicles, but did
show hemidesmosomes, anchoring filaments, and
tonofilaments.
 Repeat biopsy was sent for immunofluorescent mapping studies,
which again revealed vesicles within the basal layer. It was
notable for the presence of type IV collagen, type VII collagen,
keratin 14, laminin 332, alpha 6 integrin, beta 4 integrin, type
XVII collagen, and plectin.
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Diagnosis:
 Epidermolysis bullosa (EB) is a group of genetic
diseases characterized by blistering following friction
or minor trauma (1,2). These are broadly classified into
3 subtypes based on the location of the split during
blister formation:
EB simplex (EBS)-separation within the basal
keratinocytes
junctional EB (JEB)- separation of the basal layer of
the epidermis from the basement membrane
dystrophic EB (DEB)- separation of the basement
membrane from the dermis
Diagnosis:
 The electron microscopic images demonstrate a
relatively normal appearance of anchoring fibrils,
formed by type VII collagen, which are usually absent
in severe forms of DEB (1). On the other hand, changes
in the basal layer are somewhat suggestive of EBS,
however, EBS rarely has mucosal involvement (2).
Overall, due to his clinical appearance, the presence of
mucosal involvement, and the presence of anchoring
fibrils, JEB, the subtype with the worst prognosis, is
favored as the diagnosis
Diagnosis:
 In addition to the many described mutations known to
cause EB, it can be due to sporadic mutations, as well as
novel mutations. EB can be the result of deficiencies in the
number or function of proteins or a complete absence.
Additional genetic workup is pending on this patient, but
currently his genetic defect remains unknown. The gold
standard for diagnosis of EB remains to be electron
microscopy, as was done for this patient, but due to the
expense, inconvenience, lengthy tissue preparation, and
lack of availability, immunofluorescent microscopy is
becoming an increasingly popular alternative .
Diagnosis:
 At this time the primary treatment for all forms of EB
is supportive, but research into improved therapies is
ongoing. A recent small study demonstrated
improvement in ulcer healing through the use of
gentian violet . Encouraging results have been found
in several patients with the recessive form of DEB who
received stem cell transplants, but at this time it
remains a very risky and experimental therapy . In the
future, induced pluripotent stem cells may serve as a
method to allow gradual replacement of abnormal
skin with fully competent dermal fibroblasts and
keratinocytes .
Diagnosis:
 Many patients with genetic disorders such as EB have small
islands of normal cells due to mosaicism, with mutationed
clones that have recovered function of the disease-causing
gene in very localized patches. Current research has shown
promising results in conversion of keratinocytes and
fibroblasts into stem cells which can then be expanded and
differentiated back into skin.
 Differential Diagnosis includes other types of EB, other
genodermatoses, autoimmune bullous diseases, and
infections such as HSV, staph scalded skin, and bullous
impetigo
Case 5
 A 57 year old Haitian American female presents with a 6-month
history of asymptomatic bluish-grey patches on her anterior
neck and inferior to her eyes. She has no similar lesions
elsewhere and is otherwise healthy. Apart from Vaseline, she
does not apply any other products to her face or neck. She takes
no prescribed or alternative medications apart from a standard
multivitamin.
 On exam, bluish-grey hyperpigmented patches are apparent on
her anterior neck and inferior to her eyes. The patches parallel
her skin folds, with sparing of the central fold.
 A skin biopsy is performed. Histopathology reveals a vacuolar
interface dermatitis with prominent pigment incontinence and
pigment-laden melanophages in the upper dermis.
Erythema dyschromicum perstans
 Erythema dyschromicum perstans (EDP) was first described by
Ramirez in El Salvador in 1957. It is an asymptomatic, chronic,
slowly progressive cutaneous eruption that most common affects
dark skinned Latin Americans. The disorder has no systemic
manifestations. The etiology of EDP, although unclear, is likely
related to a cell mediated immune reaction. No triggering factor
has been consistently identified, although various pesticides,
fungicide, and medications have been reported to cause the
disorder. Clinically, EDP is characterized by slate-grey to bluebrown macules, arranged symmetrically on the trunk, neck, and
proximal extremities.
 As observed in this case, EDP affects the neck in approximately
two thirds of patients; a number of cases have also documented
periorbital involvement.
Erythema dyschromicum perstans
 Histologic features include vacuolar degeneration of the basal
layer, colloid bodies, pigment incontinence, prominent dermal
melanophages, and a perivascular mononuclear cell infiltrate in
the upper dermis.The differential diagnosis in the case includes
lichen planus pigmentosus, pigmented contact dermatitis
(Riehl’s melanosis), and idiopathic guttate macular
hyperpigmentation. Â Â Differentiation from lichen planus
pigmentosus (LPP) should be based primarily on clinical
findings, as EDP and LPP are often indistinguishable
histologically. Â Clinical features of LPP that can help in
differentiating it from EDP include: presence of associated
pruritus, associated dark-brown papules, asymmetric and sunexposed distribution of lesions, and mucosal involvement.
Erythema dyschromicum perstans
 The clinical appearance of idiopathic eruptive macular
hyperpigmentation can be very similar to EDP. However,
the vast majority of patients described with this disorder
are children or teenagers. Lesions of idiopathic eruptive
macular hyperpigmentation often spontaneously remit
over months to years.7 The histologic features of idiopathic
eruptive macular hyperpigmentation include basilar
keratinocyte hyperpigmentation and prominent dermal
melanophages.7Â Importantly, no visible basal layer
damage or lichenoid infiltrate is observed.7 This key
feature is often helpful in distinguishing idiopathic
eruptive macular hyperpigmentation from EDP.Â
Erythema dyschromicum perstans
 Pigmented contact dermatitis is a variant of contact dermatitis, often
secondary to fragrances or other cosmetic products.Clinically, as
opposed to EDP, pigmented contact dermatitis often has a brown
reticulated pattern and mild associated pruritus.8 Importantly, in this
condition, the typical manifestations of contact dermatitis
(inflammation, edema, spongiosis) are often absent. Basal liquefactive
degeneration and pigment incontinence are the predominant
histologic findings
 In patients with lesions that are clinically and histologically consistent
with EDP, especially in the distribution observed in our patient, it is
essential to obtain a careful history to identify a possible culprit
allergen. Ramirez, who originally described EDP, postulated that EDP
may be a manifestation of pigmented allergic contact dermatitis. In a
large case controlled study of 39 plantation workers in Panama with
typical lesions of EDP, 34 patients were found to have a pesticide
allergy to chlorothalonil, compared to 0 out of 41 control patients.In
this case, a triggering factor could not be identified.
Case 6
 A 40 y/o white female with past medical history of
dystonia and fibromyalgia who has been injecting
benadryl subcutaneously for the past four years for her
dystonia developed indurated plaques with ulcerations
over the injection sites over the past month. She
reports that she has pain over these sites. She states
that other than the chronic pain from her
fibromyalgia, she also has some mild intermittent
chest pain in the morning and at night,
Physical exam
 The patient has indurated plaques with ulcerations and necrosis
over the mid thighs where the patient reports injecting herself
with benadryl (fig 1 and 2)
 Laboratory studies
 The patient’s CBC, ANA, P-ANCA, C-ANCA, rheumatoid
factor, SSA, SSB. RNP and anti-smith , complement levels and
urinalysis were within normal limits. Her hepatitis panels were
also within normal limits. The patients ASO titers were high at
241 but the patient had no symptoms of an URI. Her liver
function tests were mildly elevated (ALT:121 (H), AST: 42(H),
ALP :100 and gGTP:137 (H)). Her PT, PTT, INR, Protein C, S ,
factor V, and VIII , lupus anticoagulant and cryoglobulins were
within normal limits. Tissue fungal and bacterial cultures were
negative.
Differential Diagnosis
 The differential diagnosis for this patient included
ulcerated morphea vs factitious disorder vs vasulapathy vs
vasulitis vs calciphilaxis. A punch biopsy was done in order
to differentiate between these possibilities.
 Histopathology
 Histology showed a dense fibrocollagenous tissue with a
neutrophilic infiltrate, ischemic changes (myxoid
degeneration)underlying septolobular lymphohistocytic
and foamy macrophage rich reaction with deep dermal
thrombi formation and an area of deep vasculitis
Polyarterosis Nodosa (PAN)Â vs
Nicolau syndrome
 Polyaterosis Nodosa (PAN) is a vasculitis affecting
medium sized vessels that can present as ulcers on the
lower extremities. There are approximately 4-16
million cases per million and the average age of onset
is 40-60 years of age. PAN can be limited to cutaneous
disease in 10% of cases. It can be triggered by a
streptococcus infection or HBV. Treatment of the
disease is usually with systemic corticosteroids
(1mg/kg/day) tapered over 6 months . For refractory
cases cyclophosphamide can be added. In this case,
although the patients ASO titers were mildly elevated
the patient was asymptomatic for a URI.
(PAN) vs Nicolau syndrome
 A more likely possibility in this patient is Nicolau
syndrome, which has been characterized in patients
that perform subcutaneous injections of diclofenac,
penicillin and cyanocoblamin. However, classically this
lesion displays vasculoapathy but no vasculitis (4,5).
The patient was instructed to follow up with neurology
to enquire whether subcutaneous benadryl could be
discontinued. The patient was also instructed on local
wound care. Upon discontinuation of the
subcutaneous injections of benadryl no new lesions
have developed and the older lesions are healing.
Case 7
 A 57-year old African American man with hypertension,
hepatitis C, and a remote history of IV drug abuse presented
with an acute onset pruritic erythematous outbreak over his
trunk and extremities. He was seen in the ED and evaluated, but
was told to be seen by dermatology for a consult to rule out
erythema multiforme. He denies any concurrent fevers, chills,
nausea, or vomiting or any other constitutional symptom. The
only new medication was lisinopril/HCTZ. He has no family
history of hypertension, diabetes or cancer. Social history reveals
history of smoking two-pack per day cigarette use and denies
alcohol use. On initial evaluation, a recommendation of holding
his new medication was made with topical steroid use, followed
by a biopsy. On re-evaluation, the patient was re-biopsied and
given a prednisone taper.
Case 7
 Physical Exam
 The patient had multiple annular erythematous plaques with fine scaly
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borders at the rim and centrally resolving regions of post-inflammatory
hyperpigmentation .
Laboratory Data
Hepatitis C quant was measured at 2,191,111 IU/mL with genotype 1a.
Hepatitis B quant was <300 IU/mL.
Histopathology
H&E revealed reveals marked spongiosis , eosinophils at the
dermoepidermal junction, and an underlying superficial perivascular
and interstitial infiltrate (Figure 4) composed of some lymphocytes
and histiocytes, but also numerous eosinophils . Several flame figures
are present . Neither fungal microorganisms nor basement membrane
changes are seen with interpretation of PAS histochemical stain.
Eosinophilic cellulitis (Well’s
syndrome
 George C. Wells described four cases of “granulomatous
dermatitis with eosinophilia� in 1971.Since that time,
additional case reports have been published regarding this rare
disease and have been collectively known as “eosinophilic
cellulitis.� This entity has been described as a cellulitis
because clinically, the erythema can resemble infective bacterial
cellulitis. However, other clinical presentations have also been
described, such as localized patches following Blaschko’s
lines, semicircular to annular plaques, urticarial, nodular,
papulo-nodular, and vesiculating lesions. Due to such varying
clinical presentations, the diagnosis of eosinophilic cellulitis is
often one of exclusion. Though it was originally associated with
peripheral eosinophilia, approximately 50% of eosinophilic
cellulitis cases do not have blood eosinophilia.
Eosinophilic cellulitis (Well’s
syndrome
 The histology of eosinophilic cellulitis reveals an
edematous dermis with diffuse inflammation, mixed with
focally dense infiltrations of histiocytes and eosinophils
within palisading microgranulomata. These collections
often have eosinophilic material adherent to collagen
which form “flame figures� that are scattered
throughout the dermis. The presence of flame figures are
not specific (not pathognomonic), nor diagnostic, but have
been often described in the classic histological
presentation of Well’s syndrome. Histology may also
show perivascular infiltrate of eosinophils with mixed
lymphocytes without evidence of vasculitis.
Treatments:
 Causes of eosinophilic cellulitis have included an
iatrogenic likelihood, arthropod assault, parasitic or
viral infections. For most patients, the cause is
unknown. Given its oft clinical appearance of
erythematous plaques, an active infection should be
ruled out. However, once an infection is deemed to be
unlikely, the mainstay of treatment should include oral
corticosteroids. Others have mentioned the use of
sulfone (such as dapsone), minocycline (oral
antibiotic), chloroquine.(oral antimicrobial that
reduce eosinophilic chemotaxis
Case 8
 A 47 year old African American woman presented with a
30-year history of multiple flesh-colored papules on her
face. She had no lesions elsewhere on her body. The patient
noted pruritus at the site but the lesions otherwise were
asymptomatic. She reported no history of trauma to the
area. Her medical history was significant for hypertension
and schizophrenia. Patient has been using oral Doxycycline
100mg twice daily, topical tretinoin cream every night
without improvement.
 Physical examination revealed many flesh colored
subcutaneous nodules on bilateral temples, cheeks and
jawlines, ranging in size from 2-8 mm in diameter.
Case 8
 Punch biopsy of a representative papule on the temple
was performed and the specimen was stained with
hematoxylin-eosin. Histologic examination showed
stratified squamous epithelial-lined follicular
infundibular cyst containing hair shafts that were
consistent with vellus hair cyst. No hyphae were
visualized on PAS and gram stain was negative for
bacteria.
Eruptive vellus hair cysts
 Eruptive vellus hair cysts (EVCH), a term introduced in 1977 by
Esterly et al. refers to small, distinct cystic papules with a smooth
or centrally umbilicated surface. On physical examination, these
uncommon developmental anomalies of vellus hair follicles are
typically flesh colored or yellow and firm and can extrude a
creamy, sticky substance on trauma or manipulation . They range
in size from 2 to 3mm in diameter and range in number from a
single lesion to hundreds . EVHC occur predominantly over the
anterior chest, axillae, extremities but can also rarely present on
the face, neck, groin . Age of onset varies from 2 to 64 years but
the lesions typically appear during adulthood This case is rare in
regards to age of onset, and location, face. The facial variant is
distinct in that there is no spontaneous involution and the
lesions are often slate-colored or slightly brownish-blue.
Eruptive vellus hair cysts
 Histopathologic examination revealed hyperkeratosis with cystic
structures in the mid-dermis lined by several layers of squamous
epithelial cells (4) that contained laminated keratinous material
and vellus hair shafts (2). These cystic structures arise from the
infundibulum of a hair follicle and contain multiple vellus hairs
(4). The etiology of EVHC is unknown. Some cysts exhibit an
autosomal dominant inheritance (2). A congenital pattern
associated with congenital pachyonychia or ectodermal dysplasia
has also been observed (2). Acquired or adult-onset EVHC may
be caused by follicular keratinocyte proliferation or
differentiation secondary to unknown factors, possibly trauma or
scratching. We performed a literature search for a link between
our patient's medications (ventolin, amlodipine, triamterene,
hydrochlorothiazide, risperidone) and EVHC; no link was
identified.
Eruptive vellus hair cysts
 The differential diagnosis of EVHC includes keratosis
pilaris, acneiform eruptions, folliculitis, molloscum
contagiosum, perforating dermatitis as well as milia,
pilomatricoma and steatocystoma multiplex. Cysts
should also be considered in this differential: dermoid
cysts, infundibular cysts, trichilemmal cysts.
Eruptive vellus hair cysts
 Spontaneous involution has been noted in many cases
of EVHC; thus treatment is usually unnecessary .
However, the facial variant may require treatment
because there is no spontaneous involution and
patients often have cosmetic concerns . Effective
treatment options include topical and systemic
retinoids, chemical peeling with lactic acid 12%,
washing with an abrading sponge followed by
application of urea 10% cream (6), and laser treatment
with CO2 laser or ebrium: YAG laser.
Eruptive vellus hair cysts
 Surgical options include incision and drainage,
curettage and cauterization, and needle evacuation .
EVHC are usually located deep within the skin, and
total vaporization with laser or surgical manipulation
confers a high risk of scarring and recurrence . The
combination of CO2 laser and lateral manual pressure
extraction has been reported to produce a good
cosmetic 92 result . In our case, this patient responded
well with incisions and needle evacuations
Case 9
 A 9-year-old Caucasian female with no significant past
medical history was brought in by her mother for a lesion
on the left leg. Patients mother states that this lesion has
been present for many years and was diagnosed by an
outside physician as a hemangioma. In the past, the lesion
was treated with topical steroids, injected with steroids and
also treated with pulsed dye laser (PDL), all with no
significant improvement. Following PDL treatment, the
lesion crusted but then recurred.
On physical exam, a 5.5 cm x 6.0 cm, tan, indurated plaque
with foci of papules with serosanguinous crust and purple
induration was noted inferomedial to the left knee.
Differential Diagnosis
 The appearance was atypical for a hemangioma. The
differential diagnosis included angiokeratoma vs.
lymphangioma.
 was technically imperfect.
Histopathology
 Punch Biopsy - On low magnification, below serous crust and
hyperkeratosis, a focally acanthotic epidermis is seen with ectatic
vessels predominantly in the papillary and superficial dermis. One of
these vessels appears to be contained within a collarette formed by two
rete ridges. Lumina are devoid of erythrocytes, and adjacent to some of
these vessels, a dense stromal infiltrate is noted. Smooth muscle
bundles are also noted in the mid-dermis. Higher magnification reveals
that the vessels are lined by a single layer of plump endothelial cells
and some of the ectatic vessels contain erythrocytes and some pale
pink, proteinaceous fluid. The stromal infiltrate is predominantly
lymphocytic. Cells lining the vessel wall were positive for vascular
markers, CD31 and CD34, and stained with the anti-lymphatic
antibody, D2-40. D2-40 is a monoclonal antibody against human
podoplanin which is a transmembrane mucoprotein expressed on the
surface of lymphatic endothelial cells.1 Staining with another marker
for lymphatics, LYVE-1 (lymphatic vessel endothelial hyaluronan
receptor)2
Lymphangioma circumscriptum
 Lymphangiomas are relatively rare and represent only 4% of all
vascular tumors. In children, 26% of benign vascular tumors are
classified as lymphangiomas.3 Within the category of
lymphangiomas, there are four different types – cavernous
lymphangioma, cystic hygroma, lymphangioma circumscriptum,
and progressive lymphangioma. Cavernous lymphangiomas
present as soft, fluctuant, large, diffuse, subcutaneous masses on
the head and neck, especially the oral cavity, at birth or within
the first two years of life. Cystic hygromas, a finding in Turner
syndrome (45, XO), are usually more circumscribed and found in
areas with loose connective tissue like the neck, axillae and
groin. Histologically, in both cavernous lymphangioma and
cystic hygroma, the lymphatic spaces are in the deep dermis and
subcutis. As the name suggests, cystic hygromas have multiple,
cystically dilated lymphatic spaces.
Lymphangioma circumscriptum
 Progressive lymphangioma or benign
lymphangioendothelioma presents as an
erythematous, well-circumscribed macule or plaque
on the limb of a middle-aged or elderly patient.
Histologically, irregular, thin-walled vessels dissecting
collagen in the superficial to deeper dermis are seen
without the mitoses and atypia that would be
suggestive of an angiosarcoma. Hemosiderin
deposition in the presence of lymphocytes and plasma
cells that is found in patch-stage Kaposiâ sarcoma is
also absent in benign lymphangioendothelioma.
Lymphangioma circumscriptum
 Lymphangioma circumscriptum is the most common type of
cutaneous lymphangioma, and in its classic form, presents as a >
1 cm collection of clear, rarely bloody, fluid-filled vesicles that
resemble frog spawn, on the proximal limbs or limb girdle of an
infant. The localized variant is usually < 1 cm and has variable
location and age at presentation. In contrast, similar lesions
occurring in adults in the context of chronic lymphedema or
radiotherapy are referred to as lymphangiectasia. Lesions of
cutaneous metastasis (carcinoma telangiectoides) may also
resemble lymphangioma circumscriptum clinically.
Dermatoscopic examination of lymphangioma circumscriptum
shows light brown lacunae with some redness, contingent on the
degree of extravasation. Whimster has described the postulated
pathogenesis of lymphangioma circumscriptum as defective
subcutaneous lymphatic cisterns that upon contraction dilate
superficial lymphatics, and result in vesicle formation.
Lymphangioma circumscriptum
 Histologically, below a hyperkeratotic and acanthotic epidermis,
multiple lymphatic vessels containing clear fluid and rarely
erythrocytes are found in the papillary and superficial dermis
with an adjacent lymphocytic infiltrate in the stroma.
Importantly, infantile lesions may have a large-caliber lymphatic
vessel in the subcutis that may require ligation to prevent
recurrence.4 In spite of deeper pathology, there is no connection
to the normal lymphatics and no lymphedema.6 Treatment
indications are cosmesis, persistent lymphatic drainage,
ulceration, and recurrent cellulitis. Malignant transformations
are rare and reported cases describe squamous cell carcinoma in
genital lesions.lymphangiosarcoma post-radiation of
lymphangioma circumscriptum, and a Dabska tumor (papillary
intralymphatic angioendothelioma)
Lymphangioma circumscriptum
 Challenged by local recurrence, treatment modalities for
lymphangioma circumscriptum include surgical excision,
cryosurgery, radiotherapy (with risk of malignant
transformation), laser therapy (pulsed dye, diode, carbon
dioxide, argon), intense pulsed light, suction-assisted lipectomy,
sclerotherapy, and palliative radiofrequency coagulation.
Ultrasonography and magnetic resonance imaging may be useful
in assessing the depth of involvement prior to selecting a
treatment modality. Surgical excision has the lowest recurrence
rate (17%), and is the definitive treatment of choice, especially
after the failure of other modalities, such as pulsed dye laser, to
provide symptomatic relief.Excision down to deep fascia, at the
expense of large defects and extensive scarring, and frozensection examination may further reduce recurrence rates.
Case 10
 A 32 year old Caucasian man, veteran, in previous good
health was evaluated in the clinic for a multiple year history
of painful blisters after minimal trauma, progressively
worsening. The condition was not present during his
childhood. The patient denied any constitutional
symptoms, no dysphagia, odynophagia, and no visual
abnormalities. He had no family history of blistering
disorders.
 Physical examination
 Few tense fluid and blood-filled bullae were noted over his
extremities . Areas of prior bullae healed with resultant
overlying scarring with milia formation .
Case 10
 Laboratory/Radiographic data
 During the course of his workup a pan-CT scan was
within normal limits.
 Histopathology
 Sub-epidermal split with few scattered lymphocytes
and subtle pigment incontinence Direct
immunofluorescence on salt-split skin revealed linear
IgG and C3 on the dermal side of the split.
Epidermolysis bullosa acquisita
 Epidermolysis bullosa acquisita (EBA) is a rare acquired
immunobullous disorder in which the target antigen is collagen VII.
Age of onset tends to be in adulthood, though some cases have been
described to arise in children. Its clinical spectrum is still being
defined. Though it is not hereditary, it shares clinical exam findings to
recessive dystrophic epidermolysis bullosa with non-inflammatory (at
least classically) mechanobullous skin fragility which leads to
sometimes hemorrhagic tense bullae. The natural course of the disease
leads to scar formation with milia. Lesions can appear at any
mucocutaneous surface but regions of repetitive trauma are most
susceptible, such as extensor surfaces. Some clinical features, especially
early in the course or in less severe disease, will have overlap with other
immunobullous dermatoses, making diagnosis challenging. It can
clinically mimic bullous pemphigoid (BP), bullous systemic lupus
erythematosus, mucous membrane pemphigoid, or linear IgA bullous
dermatosis.
Epidermolysis bullosa acquisita
 If suspicion for EBA exists, then a biopsy for direct
immunofluorescence is warranted with, if possible,
serology used for indirect immunofluorescence on
salt-split skin (SSS). The use of SSS helps to delineate
between BP and EBA. BP targets (BPAG180 and
BPAG230) are above the lamina lucida, whereas
collagen VII is located below the lamina lucida. Hence,
immunofluorescence on SSS will reveal a linear
staining pattern of IgG at the epidermal side for BP.
On the other hand, the staining is at the dermal side
for EBA.
Epidermolysis bullosa acquisita
 Due to its rarity, treatment choices have not been well studied.
However, responses have been attained and described through
the use of immunosuppressive therapy commonly used in
dermatology, including corticosteroids, mycophenolate mofetil,
cyclosporine, azathioprine, dapsone, cyclophosphamide, and
rituximab. In a recent review, Ishii et al. advocates the use of oral
steroids (0.5-1.0 mg/kg/day) with or without adjuvant use of
colchicine (50-100 mg daily) and/or dapsone (100-300 mg daily)
in patients with mild disease. For more moderate disease, one
can continue the above with a higher dose of colchicine at 100200 mg daily. For intractable disease, the authors advocate the
use of the higher oral steroid dose with colchicine with another
immunosuppressive agent, namely cyclosporine (3-60
mg/kg/day), plasmapheresis, IVIG, or rituximab.
Case 11
 A 78 y/o WM presented to the clinic with blisters on his
trunk. He states that the lesions were pruritic. He has
never had any oral or genital lesions. He had been
previously healthy and had been treated with high dose
prednisone in the past for this disease. He had most
recently been given IM steroids. The patient reports that
these treatments did help the lesions. However, he still
experienced breakthrough lesions. He is otherwise healthy
with no fevers, chills or night sweats.
 Physical exam
 Patient has annular, scaly plaques with peripheral pustules
with some crusting on the trunk.
Case 11
 Laboratory studies
 The patients CBC, CMP and SPEP were within normal limits.
The differential diagnosis for this patient included bullous
pempigoid, pemphigus, linear IgA and subcorneal pustular
dermatoses. A punch biopsy was done in order to differentiate
between these possibilities.
 Histopathology of first biopsy
 The histology showed midepidermal and a suprabasal
acantholoytic dermatitis that was compatible with pemphigus or
Hailey-Hailey . Clinically the presentation was inconsistent with
Hailey-Hailey disease so the patient was diagnosed with a variant
of pemphigus. However the IF was negative which is unusual for
pemphigus. This could have been because the patient had been
medically treated. It was felt that overall the pathology and the
clinical presentation fit best with an atypical pemphigus vulgaris
Atypical pemphigus vulgaris
 The patient was initially given topical clobetasol ointment,
which did not help control his disease. On the one month
f/u he was started on 10mg prednisone. This dose of
prednisone had to eventually be increased to 30mg because
the patient continued to flare. Imuran was eventually
added to his regimen. However this was only marginally
effective and the patient could not tolerate this medication
secondary to nausea. He was eventually transitioned to
500mg of Cellcept twice a day. This regimen provided
reasonable control of his disease for eight months after
which the patient had a flare of his disease at which point
another biopsy was performed.
.
Histopathology of second biopsy
 The histology again showed a suprabasal acantholytic dermatitis.
However on this biopsy there were intracorneal pustules . These
pustules contained neutrophils with a scattered focus of grampositive cocci . In the dermis there was a perivascular infiltrate
with lymphocytes, histiocytes, neutrophils and eosinophils. The
IF was again negative. Overall, this histology was consistent with
pemphigus vulgaris, Hailey-Hailey disease, a drug reaction,
infection or subcorneal pustular dermatoses. The presence of the
subcorneal pustule and bacteria made it possible that impetigo
could explain the histological presentation. However the
collection of bacteria was extremely focal and could not explain
the clinical presentation. In light of this and the negative IF the
patient was diagnosed with an atypical IgA pemphigus.
Patient course
 The patient was started on dapsone 25mg BID. This
was eventually increased to 75mg BID with good
response. The patient stated that the response
occurred within a week. Of note no monoclonal
antibodies were diagnosed on SPEP. Â However
recently the patient flared with his disease. However
there has been a question of compliance with this
regimen
Discussion
 There are four types of pemphigus. Pemphigus vulgaris, pemphigus foliaceus
and pemphigus vegetans have been well described in the literature. Another
form of pemphigus is the IgA pemphigus subgroup, which falls in the
differential of subcorneal pustular dermatoses. Patients present with pustules
that form annular plaques with crusts on the trunk, particularly on the axilla
and groin. Histologically, this disease is characterized by subcorneal pustules of
neutrophils in the epidermis with sparse acantholysis. IgA pemphigus can be
subdivided into SPD (subcorneal pustular dermatoses) and the IEN
(intraepidermal neutrophil) subtypes. The IF for this disease is positive at most
50% of the time. The SPD subtype is characterized by IgA antibodies directed
against the upper epidermis, while the IEN subtype has antibodies throughout
the entire epidermis. The IgA antibodies for SPD are directed against
desmocollin 1 while the antibodies for the IEN subtype have not been
characterized. If the IF profile is negative, the patient is usually diagnosed with
Sneddon-Wilkinson disease. However, recently there have been a few cases
of IgA pemphigus with IgG and IgA antibodies to desmoglein 1 and 3.
Discussion
 In some of these cases, the biopsy showed more
pronounced acantholysis and the IF was negative.
However, with the use of ELISA, workers were able to
show that some of these cases had IgA and IgG
antibodies to desmoglein 1 and/or 3. These cases are
very rare and some of them have associated
malignancies (e.g.: adenocarcinoma of the pancreas)
especially for the subtype with antibodies to
desmoglein 1. In the literature, these patients have
been treated with steroids and dapsone. Those that
have been treated with dapsone have had good
response.Â
Discussion
 When H.E had presented, his initial biopsy was most
consistent with pemphigus vulgaris. However, he had
relatively poor responses with frequent flares on
treatments that are effective against pemphigus vulgaris. A
subsequent biopsy showed subcorneal pustules of
neutrophils. Although this biopsy was associated with
some bacteria and a negative IF, he was diagnosed as
having IgA pemphigus. The patient was started on dapsone
with good response. This case illustrates the need for
frequent follow up for patients with bullous dermatoses
and the need to do repeat biopsies and reevaluate these
patients particularly if they are not responding to therapy.
Case 12
 A 71 yo presented to her PCP c/o fatigue and SOB of 3
months duration and a 30 lb weight loss during the
previous month. At the time of presentation, the she was
noted to have an ataxic gait and sluggish speech. The pt
was admitted directly to the hospital r/o CVA. The CVA
work-up was negative.No skin findings were noted at this
time.Three days later, dermatology was consulted
secondary to several bullae at the Bil UE.Skin biopsies and
peripheral blood flow cytometry were performed.
 Physical Exam At the Bil UE there was evidence of
hemorrhagic bullae w/ a violaceous, erythematous base.
Histopathology
 Upon microscopic examination of H&E sections at low
magnification, there was evidence of partial thickness epidermal
necrosis, a grenz zone, and a superficial and deep lymphocytic
infiltrate. A widespread, cellular infiltrate effaced the adnexa.
Upon inspection of H&E sections at increased magnification,
cells with a pale-blue cytoplasm and fine, dispersed (vesicular)
chromatin were noted. Special stains of the skin biopsy
specimen and the peripheral blood flow cytometry
demonstrated CD3/ CD20/ CDCD34 negative, CD33/ CD117
positive, and myeloperoxidase-partially positive cells.
 Follow-up
 The pt was treated with all-trans retinoic acid (ATRA) and
anthracycline-based chemotherapy. The bullous lesions resolved
in 5 to 7 days.
Acute Promyelocytic Leukemia
(APL)
 patients with APL had a 100% mortality rate. APL is a subtype of
Acute Myelogenous Leukemia (AML). It is also known as AML
with t(15;17)(q22;q12).Studies have shown its pathogenesis to be
secondary to a chromosomal translocation involving the retinoic
acid receptor alpha (RAR alpha) gene on chromosome 17 with
the promyelocytic leukemia gene (PML) on chromosome 15.It is
thought that this translocation leads to proliferation of
promyelocytic granulocytes. However, additional mutations are
likely to be required. APL is distinguished by an overt
coagulopathy at diagnosis that is 2nd to expression of tissue
factor by abnormal promyelocytes.Treatment with all-trans
retinoic acid (ATRA) allows DNA transcription and
differentiation of the immature leukemic promyelocytes into
mature granulocytes; therefore, reprograming the leukemic
promyelocytes into normally functioning cells.