Derm Flashcards
4 causes of pseudoepitheliomatous hyperplasia?
Prurigo nodularis, some deep fungal infections (including Blastomycosis), granular cell tumors, halogenodermas (iododerma, bromoderma).
Carney Complex. AKA (3)?
AKA LAMB syndrome (Lentigenes, Atrial myxomas, Mucocutaneous myxomas, Blue nevi), NAME syndrome (Nevi, Atrial myxomas, Myxoid neurofibroma, Ephelides), or Swiss syndrome. AD condition. The majority (Carney Complex type I) are caused by mutations in the PRKAR1-alpha gene on 17q24, which has been suggested to function as a tumor-suppressor gene. Carney Complex type II involves chromosome 2. 7% of all cardiac myxomas are associated with Carney complex. M=F. Mean age at Dx: 10-20 years.
DDx of Merkel cell carcinoma.
The histologic features of MCC are similar to those of various other tumors, such as metastatic small cell carcinoma, the small round cell tumors, blastic hematologic malignancies of skin/soft tissue, and melanoma. Immunostains can help distinguish them.
Examples of pseudoneoplastic lesions in the skin and their related neoplastic mimes.
Adnexal nevi [adnexal neoplasms]. Lymphoid hyperplasias [lymphomas]. Reactions to Monsel solution [sarcomas; sarcomatoid carcinomas]. Acroangiodermatitis AKA acroangiodermatitis of Mali AKA dermatitis hemostatica AKA Bluefarb-Stewart syndrome AKA pseudo-Kaposi sarcoma [Kaposi sarcoma]. Proliferating scars and posttraumatic spindle cell nodules [sarcomas; sarcomatoid carcinomas]. Intravascular papillary endothelial hyperplasia (Masson lesion) [angiosarcoma]. Pseudocarcinomatous (pseodoepitheliomatous) epithelial (epidermal) hyperplasia [squamous cell carcinoma]. Rudimentary meningocele [angiosarcoma]. Mycobacterial pseudotumors [mesenchymal neoplasms]. Bacillary angiomatosis [hemangiomas]. Other pseodoneoplasms include Der Wulst AKA central facial folliculocentric basaloid proliferation AKA hair follicle “bulges”, pseudosarcomatous fibroepithelial polyps (acrochordons), proliferative noninfectious granulomatous lesions, reactive angioendotheliomatosis, and intravascular histiocytopathy.
Grover disease.
AKA Transient Acantholytic Dermatosis. Is a self-limited, primary, nonfamilial, non-immune-mediated acantholytic skin disorder that manifests are pruritic, discrete, edematous papules and/or a vesiculopapular rash. The term TAD may be misleading, since this entity may be persistent, recurrent and show morphologies other than acantholysis. M:F = 2.4:1. The lesions are mostly on the trunk (99%) and proximal extremities (35%). Grover disease has been found to coexist with numerous other dermatoses in 11% of cases, hematologic malignancies in 8% of cases, and has also been associated with skin cancers. Histologically, the acantholysis seen in Grover disease occurs in a variety of different patterns in small, circumscribed foci, with the patterns occuring singly, or pathognomonically in combination. Patterns of acantholysis seen in Grover disease: pemphigus vulgaris-like (47%), Darier-like (18%), spongiotic (9%), pemphigus foliaceous-like (9%), mixed (9%), and Hailey-Hailey-like (8%). Pathogenesis is unknown, but a strong relationship with heat, sunlight, exercise, and bed confinement places the eccrine apparatus as a primary suspect.
Immunostains in melanocytic neoplasms in dermatopathology: S100, HMB-45, Melan-A/Mart-1, Tyrosinase, Ki-67.
S100: most sensitive marker for melanoma and spindle cell/desmoplastic melanoma. HMB-45: higher specificity for melanoma (primary-metastatic) can help distinguish nevi from melanoma. Melan-A/Mart-1: similar sensitivity and specificity to HMB-45, but with more diffuse and intense staining. Tyrosinase: higher sensitivity than HMB-45 and specificity of 97-100%, sensitivity decreases with increased clinical stage and in metastases. Ki-67: less than 5% of cells in nevi, and 13-30% of cells in malignant melanoma; higher percentages have been noted in Spitz nevi as well.
Lentigo maligna.
The preinvasive/in situ form of melanoma located on chronically sun-damaged skin. The appellation lentigo maligna has been used b/c of the lesion’s clinical resemblance to an actinic/solar lentigo and/or b/c of some authors’ unwillingness to label these lesions as a malignancy per se. Most patients present with a slowly enlarging macule or patch. Areas of partial regression within the lesion are not uncommon. Amelanotic lentigo maligna may develop spontaneously or may arise from a previously treated pigmented lentigo maligna. Histologic features related to chronic sun damage such as epidermal atrophy, increased pigmentation in basal keratinocytes, and prominent solar elastosis are present. The melanocytes are increased in number, and as in solar lentigenes, often are disposed as single cells along the basal layer. Nests of melanocytes may be present, but are unevenly distributed across the lesion. A few melanocytes may permeate superficial epidermal layers; involvement of cutaneous adnexal structures is common. Nuclear atypia is variable and may be subtle.
Lichen planus vs. lichenoid drug eruption?
LDE should be considered in all pts with clinical features of LP. LDE may appear clinically and histologically identical to LP. The drugs MC associated with LDE are ACEIs, thiazides, beta-blockers, gold salts, antimalarial agents, and penicillamine. The mean age of onset is ~60 yo, about 10 years later than idiopathic LP. LDE has a variable latency period of weeks to years that is dependent on multiple factors. Although the pathogenesis of LDE is unclear, offending drugs likely alter epidermal proteins, acting as haptens to induce an immune response. Idiopathic LP is characterized by monomorphic, violaceous, shiny, flat-topped papules and plaques, characteristically with a fine reticulated pattern of white scale (Wickham striae, which is the macroscopic correlate to histologic hypergranulosis). The flexural surfaces of the wrists, anterior lower legs, and mucous membranes are often affected. LDE is often more polymorphic and may include lesions with a more eczematous, scaly appearance, and is also more likely to present with an atypical distribution of lesions, esp truncal or photodistribution, and to resolve with more pronounced hyperpigmentation. Characteristic histologic features of idiopathic LP include a dense band-like lymphocytic infiltrate at the dermal-epidermal junction, damage to the basal layer, colloid bodies (eosinophilic hyaline bodies originating from apoptosed keratinocytes), irregular acanthosis with “saw-toothed” rete ridges, and overlying hypergranulosis. Although no histologic features can reliably distinguish between idiopathic LP and LDE, certain findings such as the presence of eosinophils, plasma cells, focal parakeratosis, and a deeper perivascular infiltrate may support a diagnosis of LDE.
Metastatic Crohn disease.
MCD is an entity characterized by cutaneous, noncaseating granulomas at sites anatomically separate from the GI tract. It is the least common dermatologic manifestation of Crohn disease. In adults, the age of onset of MCD ranges from approximately 29 to 39 years, and the majority of patients have a previous diagnosis of Crohn disease. Twenty percent of patients with MCD may present without classical manifestations of Crohn disease. In these patients, Crohn disease manifests in 2 months to 4 years after the initial presentation of MCD. Cutaneous lesions of MCD may present as papules, plaques, nodules, and ulcerations, which may involve the arms, legs, genitalia, and face. Lesions have also been noted to have predilection for the moist environment of skin folds, including submammary and abdominal creases as well as the perineal and inguinal regions. MCD may present as a solitary lesion or occur in multiple sites and may be painless or tender upon palpation. In the pediatric population, MCD typically presents from the ages of 10 to 14, with about 50% of these patients having concurrent Crohn disease. Of these patients, approximately one-half have active gastrointestinal symptoms. In children who present with MCD lesions without evidence of Crohn disease, subsequent onset of gastrointestinal manifestations occurs from 9 months to 14 years after the initial presentation of MCD. The genitalia appear to be the most common area of involvement in children with MCD; the most common cutaneous manifestation presents as labial, penile, and/or scrotal swelling with or without accompanying erythema. Genital ulcerations have also been reported. MCD presents microscopically as sterile, noncaseating granulomatous inflammation located primarily in the superficial papillary and deep reticular dermis with occasional extension into the subcuticular fat. The granulomas consist of Langerhans giant cells, epithelioid histiocytes, lymphocytes, and occasional plasma cells. The underlying etiology of MCD is currently unknown. It has been suggested that antigens or immune complexes stemming from the GI tract in primary Crohn disease travel through the circulatory system and deposit in the skin, creating perivascular granulomatous features seen on microscopic examination of MCD lesions. Autoimmune cross-reactivity has also been suggested, where antibodies specific to antigens in the GI tract that may be responsible for inflammatory Crohn disease react with skin antigens of similar structure. The differential diagnosis of MCD consists of any granulomatous entities that may involve the skin, including but not limited to cutaneous sarcoidosis, erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, mycobacterial disease, and foreign body reaction.
Painful skin lesions mnemonic (variation 1 of 3).
ANGEL: Angiolipoma, Neuroma, Glomus tumor, Eccrine spiradenoma, Leiomyoma.
Painful skin lesions mnemonic (variation 2 of 3).
LEND AN EGG: Leiomyoma, Eccrine spiradenoma, Neuroma, Dermatofibroma (sometimes), Angiolipoma, Neurilemmoma, Endometrioma, Glomus tumor, Granular cell tumor.
Painful skin lesions mnemonic (variation 3 of 3).
BLUE ANGEL: BLUE rubber bleb nevus, Angiolipoma, Neuroma, Glomus tumor, Eccrine spiradenoma, Leiomyoma.
What is seen histologically in skin and GI biopsies from patients with acute GVHD?
The skin biopsy initially shows epidermal basal vacuolization and focal epidermal apoptosis with lymphoid infiltration. Bullae formation with epidermal separation can extend to erythroderma, and necrosis is observed in later stages. In grade I, there is vacuolization of the basal keratinocytes; in grade II, there are dyskeratotic keratinocytes and basal cell vacuolization; in grade III, there is increased keratinocyte necrosis and focal basal layer clefting; in grade IV, there is necrosis of the entire epidermis and complete separation from the dermis. There are various degrees of lymphocytic infiltration. The microscopic findings of early GVHD are similar to erythema multiforme, while the severe form resembles toxic epidermal necrolysis.
The GI biopsy shows diffuse edema and mucosal swelling followed by variable crypt cell apoptosis (“exploding” crypts) and a mixed chronic and predominantly lymphoplasmacytic infiltrate, and there can be crypt dropout. In grade I, there is increased crypt apoptosis; in grade II, there is apoptosis with crypt abscess; in grade III, there is crypt necrosis; in grade IV, there is total denudation of mucosal areas. The immunosuppressive drug mycophenolate mofetil can cause variable GI mucosal injury patterns, including GVHD-like changes.
In the skin and GI tissue affected by GVHD, the mechanism of apoptosis is likely similar and caused by alloreactive T lymphocytes targeted to alloantigen on recipient tissue.
Erysipelas is caused by (organism). Erysipeloid is caused by (organism).
Erysipelas is caused by S. pyogenes. Erysipeloid is caused by Erysipelothrix rhusiopathiae.
Adiaspiromycosis is caused by (organism).
Adiaspiromycosis is caused by Chrysosporium parvum.
Define the following terms: acantholysis, acanthosis, bulla, epidermolysis, lichenoid interface change, spongiosis, vacuolar interface change.
Acantholysis is disruption of desmosomes that normally join the keratinocytes of the epidermis, resulting in loss of cohesion and rounding up of the affected cells. Acanthosis is an increase in the thickness of the stratum malpighii. A bulla is an intraepidermal or subepidermal cavity. Intraepidermal bullae may be secondary to either spongiosis or acantholysis. Subepidermal bullae are formed from extensive papillary dermal edema. Epidermolysis is a distinctive alteration of the granular layer characterized by perinuclear clear spaces, swollen and irregular keratohyalin granules, and an increase in the thickness of the granular layer. Lichenoid interface change results from destruction of basal keratinocytes. Destruction and dyskeratosis result in “remodeling” of the basement membrane zone. A bandlike lymphocytic infiltrate usually accompanies the keratinocyte changes. Spongiosis is intercellular intraepidermal edema. Vacuolar interface change results from destruction of the basal keratinocytes characterized by the presence of intracytoplasmic vesicles. The vesicles enlarge, and eventually the basal keratinocytes die; as a result, the integrity of the basal zone of the epidermis is lost.
What are the 4 layers of the epidermis?
The stratum corneum is the outermost layer of the epidermis. The fully keratinized cells of this layer are flattened and devoid of nuclei. On acral surfaces, a thin stratum lucidum (clear zone) is present between the stratum corneum and the stratum granulosum. The stratum granulosum is named for the prominent deeply basophilic keratohyalin granules found in flattened keratinocytes. Deep to the stratum granulosum is the stratum spinosum, which is characterized by abundant eosinophilic cytoplasm, ovoid nuclei, and intercellular bridges. The stratum basale (basal cell layer) is the undulating row of cuboidal to columnar cells with minimal cytoplasm and contain proliferating cells for epidermal renewal. The basal cells attach to the basement membrane of the epidermis. The stratum spinosum and the basal cell layer are collectively referred to as the stratum malpighii.
What HPV types (in order of frequency) are seen mostly commonly in the following lesions? Plantar wart, common wart, flat (juvenile) wart, oral squamous papilloma, oral focal epithelial hyperplasia (Heck disease), epidermodysplasia verruciformis, laryngeal papillomas, condyloma acuminatum, cervical LSIL, cervical HSIL, cervical AIS and invasive cervical adenocarcinoma.
Plantar wart: 1, 2. Common wart: 2, 1, 4, (HPV 7 in fish and meat handlers). Flat (juvenile) wart: 3, 10. Oral squamous papilloma: 6, 11. Oral focal epithelial hyperplasia (Heck disease): 13, 32. Epidermodysplasia verruciformis: 2, 3, 10, 5, 8. Laryngeal papillomas: 6, 11. Condyloma acuminatum: 6, 11. Cervical LSIL: 6, 11. Cervical HSIL: 16, 18, 31, 33, 35. Cervical AIS: 18. Invasive cervical adenocarcinoma: HPV 16 and 18 are detected with equal prevalence in most subtypes of cervical adenocarcinoma.
What are Henderson-Patterson bodies?
Henderson-Patterson bodies = molluscum bodies, seen in molluscum contagiosum. They are eosinophilic intracytoplasmic inclusion bodies (accumulated virus particles) in keratinocytes of stratum spinosum and stratum granulosum.
What is myospherulosis?
Myospherulosis, AKA spherulocytosis AKA subcutaneous spherulocystic disease, is an iatrogenic benign mass formed by a foreign body-type granulomatous reaction to lipid-containing material and blood. Clinically, there are solid subcutaneous or dermal nodules. Grossly, is a large saccular cyst-like lesion Histologically, there are saclike structures with fungi-like spherules. The spherules are composed of erythrocytes damaged by endogenous and exogenous fat. The damaged erythrocytes are enclosed by a lipid membrane and later phagocytosed by histiocytes as part of the lipogranulomatous reaction that takes place in adipose tissue. The walls of the spherules are formed due to the physical emulsion phenomenon that occurs between lipid-containing materials and blood. Myospherulosis can be a result of fat necrosis, malignancy such as RCC, endogenous membranocystic degeneration of fat that occurs in lupus, or lipid/petrolatum-based medications being injected or applied to open wounds. It is called MYOspherulosis due to the involvement of skeletal muscle in some patients. It can be mistaken for true fungus, such as Coccidioides, because myospherulosis has parent bodies/pigmented bodies and spherules/endobodies that are similar in size and morphology to Coccidioides; however, myospherulosis has pigmented bodies, while Coccidioides is never pigmented.
What are the 3 main types of multinucleated giant cells?
Foreign body giant cells, Langhans giant cells, and Touton giant cells. All three types are transformed macrophages; mononuclear phagocytes fused under the influence of cytokines. Foreign body giant cells have nuclei that are randomly distributed but often aggregate as centrally located, overlapping nuclei. Langhans giant cells have a peripheral ring-like arrangement of nuclei in an arcuate configuration but no rim of clear cytoplasm. Touton giant cells have a ring of nuclei separating a peripheral clear or foamy rim of cytoplasm from central, more eosinophilic cytoplasm. The peripheral cytoplasm appears clear due to high lipid content. Touton giant cells are seen in lesions with high lipid content, such as xanthomas, xanthogranulomas, and fat necrosis. Touton giant cells can also be seen in dermatofibroma. Other types of multinucleated giant cells include epithelium-derived MGCs, which can be prominent in certain viral infections such as measles (Warthin-Finkeldey cells), RSV, HSV/VZV, and parainfluenza. Also, MCGs derived from neoplastic cells may be formed in a variety of neoplasms.
Does Merkel cell carcinoma stain with TTF-1?
No.
When is SLN biopsy indicated in melanoma, according to ASCO and Society of Surgical Oncology guidelines?
SLN bx is recommended for intermediate-thickness melanomas (Breslow thickness 1-4 mm) of any anatomic site for accurate staging. SLN bx may be indicated for thick melanomas (T4, Breslow thickness >4 mm) for staging and to facilitate regional disease control. Evidence does not support routine SLN bx of thin melanomas (<1 mm) except with high risk features (ulceration, mitotic rate 1/mm^2 or greater, Breslow thickness 0.75-0.99 mm) when benefits of staging outweight risks of the procedure. Complete lymph node dissection is recommended for all patients with a positive SLN bx.
What is a Triton tumor?
A benign Triton tumor is a neuromuscular hamartoma/choristoma. It is a rare developmental lesion of mature skeletal muscle and nerve. Microscopically, is made up of multiple nodules, each 3-5 mm, separated by narrow bands of connective tissue. Nodules are composed of fasicles of striated muscle of varying size with nerve fibers (myelinated or not) within same perimysial fibrous sheath. Stroma may be more cellular with bland spindle cells and resemble fibromatosis. A malignant Triton tumor is made up of both malignant schwannoma cells and malignant rhabdomyoblasts, and is classified as a MPNST with rhabdomyosarcomatous differentiation. The name “triton” was first used in reference to observation of supernumerary limbs containing bone and muscle growing the backs of tritons (a name given to some species of sea snails) after the implantation of the sciatic nerve into the soft tissues of the back.
What is the difference between epidermotropism and exocytosis in dermpath?
Epidermotropism is lymphocytes in epidermis with relative absence of spongiosis: term usually reserved for mycosis fungoides. Exocytosis is lymphocytes in the epidermis with associated spongiosis: term usually used when discussing spongiotic dermatitis.
What are Medlar bodies?
Medlar bodies, also called chromo bodies, are the adaptive tissue form (“sclerotic cells”) of a specific group of dematiaceous fungi that cause chromoblastomycosis. They are round, brown, thick-walled structures that are 4-12 µm in diameter, resembling overlapping copper pennies. They divide by septation, resembling hot-cross buns.
Chromoblastomycosis is also called ___.
Chromoblastomycosis is also known as “Chromomycosis,” “Cladosporiosis,” “Fonseca’s disease,” “Pedroso’s disease,” “Phaeosporotrichosis,” and “Verrucous dermatitis.” It is a long-term fungal infection of the skin and subcutanous tissue (a chronic subcutaneous mycosis). The infection occurs most commonly in tropical or subtropical climates, often in rural areas. It is caused by specific types of dematiaceous fungi which become implanted under the skin, often by thorns or splinters. The term chromoblastomycosis is restricted to the cases in which sclerotic cells/Medlar bodies/chromo bodies (an adaptive tissue form of the fungi) are present in tissue.
What is a BLK in dermpath? What is the clinical presentation and epidemiology?
Benign lichenoid keratosis, also called lichenoid benign keratosis, lichen planus-like keratosis (LPLK), solitary lichen planus, and involuting lichenoid plaque. BLKs are usually solitary, discrete, slightly raised lesions of short duration, measuring 3-10 mm in diameter. The sudden appearance of the lesion is often a striking feature. Lesions are violaceous or pink, often with a rusty tinge. There may be a thin, overlying scale. There is a predilection for the arms and presternal area of middle-aged and elderly women. Lesions are sometimes mildly pruritic or “burning.” Clinically, BLK is usually misdiagnosed as a BCC or Bowen’s disease. BLK is a heterogeneous condition which usually represents the attempted cell-mediated immune rejection of any of several different types of epidermal lesion, most often solar lentigo.
Benign lichenoid keratosis (BLK)/Lichen planus-like keratosis (LPLK) histologic appearance.
There is a florid lichenoid reaction pattern with numerous apoptotic keratinocytes in the basal layer and accompanying mild vacuolar change. The infiltrate is usually quite dense and often includes a few plasma cells, eosinophils, and even neutrophils in addition to the lymphocytes and macrophages. The infiltrate may obscure the dermo-epidermal interface. Pigment incontinence may be prominent. This is so in the late (regressed, atrophic) stage; epidermal atrophy and papillary dermal fibrosis are also present. There may be mild atypia of keratinocytes but this is never as marked as it is in a lichenoid solar keratosis. There is often mild hyperkeratosis and focal parakeratosis. The presence of parakeratosis allows a distinction to be made with lichen planus. Hypergranulosis is not as pronounced as in lichen planus. A contiguous solar lentigo or large cell acanthoma is sometimes seen.
A small subset of cases of the polyostotic form of fibrous dysplasia (~3%) occurs along with endocrine abnormalities and coast of Maine cafe-au-lait spots, a triad called ___ syndrome.
A small subset of cases of the polyostotic form of fibrous dysplasia (~3%) occurs along with endocrine abnormalities and coast of Maine cafe-au-lait spots, a triad called McCune-Albright syndrome.
Kaposi sarcoma overview.
Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy–related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma–like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. KS remains one of the most common AIDS-defining malignancies.
Kaposi sarcoma pathogenesis.
With the advent of genomic technologies, proliferating KS spindle tumor cells are now known to be of endothelial origin, confirming former studies that used histochemistry and ultrastructural findings. Circulating blood mononuclear and endothelial “progenitor cells” are believed to be the source of early KS lesions. Infection with HHV8 reprograms the host’s blood endothelial cells so that they resemble lymphatic endothelium, upregulating several lymphatic-associated genes such as lymphatic vessel endothelial receptor 1 (LYVE1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR3). However, HHV8 infection alone appears to be insufficient for the development of KS. Kaposi sarcoma progression relies also on some degree of host immune dysfunction and the local inflammatory milieu. Kaposi sarcoma growth involves the upregulation of many key HHV8 gene products, such as the latency-associated nuclear antigen (LANA-1 or LNA-1). Like other herpesviruses, HHV8 remains latent within cells and has developed a variety of mechanisms to evade the host immune system.
For the 4 types of Kaposi sarcoma, list the epidemiology, clinical distribution, and behavior.
Classical type: Mainly males aged 40-70 years, of Mediterranean or Jewish Ashkenazi origin. Skin of the lower extremities, but mucosal and visceral lesions may develop. Indolent. African type: Middle-aged black adults and children from equatorial Africa. Multiple localized skin tumors, involving lower extremities and/or lymph nodes. Progressive; lymphadenopathic form is aggressive. AIDS-associated type: Mainly homosexual males and IVDUs aged 20-50 years; now equally affects women and children in Africa. Disseminated mucocutaneous and visceral involvement. Aggressive; lesions may regress or flare with initiation of antiretroviral therapy. Iatrogenic type: Immunosuppressed persons of any age from autoimmune disease, drugs, or transplantation. Localized mucocutaneous or disseminated KS, with possible visceral lesions. Variable; may regress after immunosuppression is discontinued.
Histologic appearance of Kaposi sarcoma.
Early patch-stage KS is characterized by abnormal vessels lined by thin endothelial cells dissecting the dermis. Ramifying proliferating vessels often surround larger ectatic vessels and skin adnexa, producing the so-called promontory sign. This sign is not pathognomonic for KS, as it has also been described in other vascular lesions including benign vascular tumors and angiosarcoma. Sparse chronic inflammatory cells, extravasated red blood cells, and hemosiderin-laden macrophages are frequently present in patch KS lesions. These early histologic changes may be inconspicuous, and for that reason can be easily missed on biopsy. Plaque-stage KS lesions are characterized by a proliferation of both spindle cells and vessels, which in the skin involve most of the dermis, and sometimes even the subcutis. Well-developed KS tumors consist of several fascicles of these spindle-shaped tumor cells, often admixed with a variable chronic inflammatory infiltrate composed of lymphocytes, plasma cells, and dendritic cells. Kaposi sarcoma lesions also contain several hemosiderin-laden macrophages. Iron staining may help distinguish KS from similar-appearing interstitial granuloma annulare lesions that lack iron. In cross section, KS nodules display a sievelike appearance caused by the transection of spindle cells with intervening slitlike spaces. Eosinophilic and PAS–positive hyaline globules are a common finding in advanced KS lesions. These globules may be located within lesional cells or extracellularly. Typical KS lesions are devoid of marked cellular pleomorphism, necrosis, or a significant number of mitotic figures. In rare instances, AIDS-KS lesions may harbor concomitant pathologic findings, usually an opportunistic pathogen (eg, cryptococcosis, mycobacterial granulomas, or molluscum contagiosum).
What are pre-Kaposi sarcoma lesions and anaplastic Kaposi sarcoma?
These are at the two opposite ends of the spectrum of Kaposi sarcoma. Pre-KS lesions are also referred to as an “in situ” form of KS. These pre-KS lesions are characterized by groups of abnormal capillary-like vessels admixed with an inflammatory infiltrate, similar to patch-stage KS lesions. They are associated with lymphangiogenesis arising in the setting of chronic lymphedema. On the other end of the spectrum is anaplastic KS, sometimes referred to as pleomorphic KS. Anaplastic KS is an infiltrative, solid proliferation of spindle cells without vascular spaces, seen mainly in AIDS involving acral sites. This aggressive variant displays a greater degree of cellular and nuclear atypia, high mitotic index (eg, 5 to 20 mitoses per 10 high-power fields), and occasional necrosis.
IHC for Kaposi sarcoma.
Kaposi sarcoma lesional cells stain positively with the endothelial markers factor VIII–related antigen, CD31 (PECAM-1), and CD34. CD34 tends to show stronger expression than CD31 in advanced-stage lesions of KS. KS spindle cells also express several lymphatic specific markers such as D2-40 (which binds to the podoplanin antigen), LYVE-1 (a homologue of the CD44 glycoprotein receptor for hyaluronan), VEGFR-3 (the receptor for vascular endothelial growth factor C), and Prox-1. Bcl-2 also shows positivity in KS, related to the tumor’s mechanisms of resisting apoptosis. The identification and localization of HHV8 within KS lesional cells by using LNA-1 (also called LANA-1) is the most diagnostically helpful immunostaining technique available to differentiate KS from its mimics. LNA-1 immunoreactivity in KS cells appears as stippled nuclear staining. However, HHV8 is not entirely limited to KS and has been detected in some angiosarcomas, hemangiomas, and dermatofibromas. LNA-1 IHC is favored over PCR detection of HHV8 in the evaluation of problematic vascular proliferations because contaminating mononuclear inflammatory cells may also harbor this herpesvirus, especially in HIV-positive patients.
Histologic differential diagnosis for the patch, plaque, and nodular stages of Kaposi sarcoma.
Clinical history, such as HIV infection or status post transplant, may strongly support the diagnosis of KS. The differential diagnosis of patch-stage KS includes targetoid hemosiderotic hemangioma, fibrous histiocytoma, and interstitial granuloma annulare. The differential diagnosis of plaque-stage KS includes tufted angioma, targetoid hemosiderotic hemangioma, microvenular hemangioma, and acroangiodermatitis (“pseudo-Kaposi sarcoma”). The differential diagnosis of nodular KS includes bacillary angiomatosis, other vascular tumors (eg, spindle cell hemangioma and Kaposiform hemangioendothelioma), fibrohistiocytic tumors (eg, cellular, angiomatoid, and atypical variants of fibrous histiocytoma, and dermatofibrosarcoma protuberans), resolving dermal fasciitis, spindle cell melanoma, and several other spindle cell mesenchymal neoplasms (eg, cutaneous leiomyosarcoma).
What are nonmalignant medical conditions associated with reactive eosinophilia?
Allergic reactions (drug reactions, asthma), parasitic infections (strongyloidiasis), schistosomiasis, filariasis, toxocariasis), metabolic abnormalities (adrenal insufficiency), humoral immunodeficiency (hyperimmunoglobulin E syndrome (Job syndrome), Wiskott-Aldrich syndrome, hyperimmunoglobulin M syndrome, immunoglobulin A deficiency), pulmonary eosinophilias (eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), allergic bronchopulmonary aspergillosis, chronic and acute idiopathic eosinophilic pneumonias), autoimmune blistering skin diseases (dermatitis herpetiformis, bullous pemphigoid).
How can angiolymphoid hyperplasia with eosinophilia be distinguished from Kimura lymphadenopathy?
ALHE can have a striking histologic similarity to KL. ALHE is present mostly in Caucasians and can be confused with early stage KL. ALHE more often affects females and is seen in soft tissues and superficial dermis forming clusters of eosinophilic cells. ALHE typically presents as cutaneous papules rather than a mass lesion, and histology reveals non-nodal collections of eosinophils with hypertrophic endothelial cells that protrude and occlude vascular lumina in a tombstone pattern. Lymphadenopathy, which is an essential feature in KL, is not frequently seen in ALHE.
Several named syndromes are associated with eosinophilia and eosinophilic infiltration of specific organs: eosinophilic cellulitis (__ syndrome), eosinophilic pneumonia (__ syndrome), eosinophilic fasciitis (__ syndrome), and eosinophilic vasculitis (__ syndrome).
Several named syndromes are associated with eosinophilia and eosinophilic infiltration of specific organs: eosinophilic cellulitis (Well syndrome), eosinophilic pneumonia (Loeffler syndrome), eosinophilic fasciitis (Shulman syndrome), and eosinophilic vasculitis (Churg-Strauss syndrome).
What are some entities that cause a sinus pattern of nonneoplastic proliferation in lymph node?
Sinus histiocytosis, a nonspecific reaction to numerous lymph node stimuli. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Lymphangiogram effect. Whipple disease. Hemophagocytic syndrome. Dermatopathic lymphadenitis.
What is a white sponge nevus?
AKA Cannon disease AKA familial white folded mucosal dysplasia AKA hereditary leukokeratosis. An AD disease with incomplete penetrance and variable expressivity. Prominent parakeratosis, acanthosis, and spongiosis of nonkeratinized squamous mucosa. Rete are blunted. Inflammation is usually not present. Pathognomonic: Pap stain of exfoliative cytology shows a characteristic perinuclear eosinophilic condensation of keratin tonofilaments. Most commonly intraoral, with buccal mucosa most common intraoral site. DDx: hereditary benign intraepithelial dyskeratosis, leukoedema, oral hairy leukoplakia.
What is hairy leukoplakia AKA oral hairy leukoplakia?
An EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression. Micro: Marked acanthosis and parakeratosis. Epithelial hyperplasia with elongation of rete ridges. Viral cytopathic effect (balloon cells) in spinous layer. Candida can be seen in superficial keratin - coinfection is a common finding in OHL. Very little if any inflammation. No dysplasia. DDx: Frictional keratosis. Hyperplastic candidiasis. Leukoplakia. Lichen planus.
Is oral hairy leukoplakia an AIDS-defining illness?
No. OHL is an EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males but seen in transplant patients as well. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression.
What is herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause. Transmission is direct contact, usually oral-fecal route.
What virus is the most common cause of herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause, but other coxsackie viruses usually associated include A1 to A6, A8, A10, or A22.
What is hand, foot, and mouth disease?
A common viral illness of infants and children, which causes fever and blister eruptions of mouth and/or skin. Caused by virus belonging to Enterovirus group. Transmission is by direct contact. Virus is found in secretions, including saliva, nose and throat secretions, blister fluid, and stools.
What is Heck disease?
AKA focal epithelial hyperplasia AKA multifocal epithelial hyperplasia. A benign, virus-induced epithelial proliferation of oral mucosa associated with HPV types 13 and 32. Majority of cases are in children. Micro: Prominent acanthosis and elongated broad rete ridges (since the thickened epithelium extends upward, elongated rete are at same depth as adjacent normal rete ridges). May see papillary surface. Mitosoid cells (represents ballooning and nuclear degeneration; represents an altered nucleus resembling a mitosis in an otherwise normal stratified squamous epithelium; can be seen throughout epithelium); do not misinterpret mitosoid cells as atypia. Koilocytic change in superficial keratinocytes can be seen. No dyskeratosis and/or atypia. DDx: Papilloma. Condyloma acuminatum. Oral verruca vulgaris.
What HPV types cause Heck disease (focal epithelial hyperplasia/multifocal epithelial hyperplasia)?
HPV types 13 and 32.
What sites are affected in pemphigus vulgaris?
PV is an autoimmune mucocutaneous disease characterized by intraepithelial blistering. Etiology is circulating autoantibodies to desmoglein 1 and 3 adhesion molecules of squamous epithelium, which inhibit cell-cell adhesion resulting in acantholysis and blister formation. Mucous membranes: oral, nasal, esophagus, larynx, nasopharynx, conjunctivae, genitalia, anal mucosa. Cutaneous sites are mostly on intertriginous areas, trunk, head, and neck. Mucosal PV may be the only manifestation of disease or may precede cutaneous PV by an average of 5 months. >90% of patients will have oral involvement during disease course.
What is the etiology of pemphigus vulgaris?
PV is an autoimmune mucocutaneous disease characterized by intraepithelial blistering. Etiology is circulating autoantibodies to desmoglein 1 and 3 adhesion molecules of squamous epithelium, which inhibit cell-cell adhesion resulting in acantholysis and blister formation (suprabasal bullae formation with intraepithelial clefting).
What is the characteristic direct immunofluorescence finding in pemphigus vulgaris?
Homogenous staining (“fishnet” pattern) of IgG in intercellular desmosomal areas at all levels of the epidermis.
What sites are affected in mucous membrane pemphigoid AKA cicatricial pemphigoid?
MMP is a chronic, blistering mucocutaneous autoimmune disease generally presenting in 6th or 7th decade and M:F=1:2. Oral cavity is frequently affected, with gingival involvement seen in >60%. Ocular lesions occur in ~40% of patients with oral MMP. Upper aerodigestive tract can also be affected. Micro shows subepithelial clefting, intact basal cells, and a sparse inflammatory cell infiltrate in superficial lamina propria.
What is the characteristic direct immunofluorescence finding in mucous membrane pemphigoid (cicatricial pemphigoid)?
Micro shows subepithelial clefting, intact basal cells, and a sparse inflammatory cell infiltrate in superficial lamina propria. Direct immunofluorescence shows a continuous linear band of IgG and C3 at basement membrane zone (can also see IgM and IgA).
What is seen in direct immunofluorescence of lichen planus?
DIF is not specific or diagnostic. May show linear or granular deposits of fibrin or fibrinogen. Deposits of C3, IgM, IgG, and IgA occasionally seen.
What is Riga-Fede disease?
AKA traumatic ulcer, traumatic ulcer with stromal eosinophilia, eosinophilic granuloma of tongue, traumatic granuloma, atypical histiocytic granuloma. It is a chronic traumatic ulceration of oral mucosa with unique histopathologic features. Riga-Fede disease specifically refers to trauma to the soft tissue (ventral tongue or inner lower lip) in newborns or infants from natal or neonatal teeth. In children, traumatic ulcer is often due to thermal or electrical burns or parafunctional habits. In adults, traumatic ulcer is often due to fractured and/or malposed teeth or parafunctional habits. Micro: Ulcer bed composed of granulation tissue with mixed inflammatory cell infiltrate of lymphocytes, histiocytes, neutrophils, and occasionally plasma cells. Inflammation including scattered eosinophils extends into underlying muscle.
What oral lesions are associated with pseudoepitheliomatous hyperplasia?
Granular cell tumor. Hyperplastic candidiasis. Inflammatory papillary hyperplasia. Median rhomboid glossitis. Necrotizing sialometaplasia. Mucosal ulcers (traumatic ulcers, aphthous ulcers, herpetic ulcers, nonhealing extraction sockets). Although PEH can have rete deeply extending into lamina propria, anastamosing of rete, and keratin pearl formation, there will be no or very little cytologic atypia, and while mitotic figures can be present, they will not be atypical.
