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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 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.  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. 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.  The patient has no other known medical issues. 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.1 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. 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.   Differentiation from lichen planus pigmentosus (LPP) should be based primarily on clinical findings, as EDP and LPP are often indistinguishable histologically.  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.7 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. 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) 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 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 eosinophiliaâ€� in 1971.Since that time, additional case reports have been published regarding this rare disease and have been collectively known as “eosinophilic cellulitis.â€� 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 figuresâ€� 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.  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. 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.