Answers to Image of the Month 2020, 2021, 2022 and 2023
Case contributed by Dr Savera Gupta and Dr Vidya Kharkar
Cutaneous gouty tophi
On biopsy, it shows multiple well demarcated dermal deposits of fluffy, amphophilic, amorphous material, which at places are surrounded by thin rim of histiocytes and few multinucleated giant cells.
Additional comments: When tophi are suspected, it is preferable to use absolute ethanol or ethanol based fixative (example: Carnoy fluid) instead of formalin. This is because formalin is aqueous based which dissolves the urate crystals and the characteristic morphology of closely packed (like bundles or sheaves) refractile needle shaped brownish crystals is lost, leaving only amphophilic amorphous deposits (as seen in this case). The presence of granulomatous reaction with histiocytes and giant cells surrounding the deposits is a common finding. At times, secondary calcification and ossification may take place in urate crystals, especially in long standing cases. Calcium deposits can be easily recognized (and differentiated from urate crystals) as amorphous, uniformly staining basophilic material imparting a deep blue color on routine H & E stain.
Case contributed by Dr Mithilesh Chandra
Lupus miliaris disseminatus faciei (LMDF) with epidermal cyst
LMDF is a chronic granulomatous disorder presenting as skin-coloured to yellowish-brown papules and pustules that leave behind pock-like scars, predominantly distributed on the centrofacial area, including the periorbital region. Atypical feature includes presence of nodulo-cystic lesions.
On biopsy, epidermis shows follicular plugging. Dermis shows an epidermal cyst with lamellated keratin. The cyst wall in the lower part is replaced and surrounded by dense granulomatous infiltrate composed of lympho-histiocytes, Langhans' and foreign body giant cells along with prominent areas of caseous necrosis. The presence of caseous necrosis is typical of LMDF and is not seen in ruptured epidermal cysts. LMDF with co-existing epidermal cyst has been rarely described in literature and it is hypothesized that rupture of cyst may be related to appearance of LMDF.
Case contributed by Dr Mithilesh Chandra
Inverted follicular keratosis with cutaneous horn
Inverted follicular keratosis is a benign tumor of the follicular infundibulum, regarded as a variant of seborrheic keratosis or verruca vulgaris. It presents as a solitary nodular or filiform lesion on the head and neck.
On biopsy, it is an endophytic tumor with finger-like projections of the tumor cells extending into the dermis. The tumor cells are composed of basaloid cells at the periphery and large keratinizing cells towards the center. It has keratoacanthoma- like pattern with marginal buttress formation. The characteristic feature is the presence of squamous eddies formed by concentric layers of squamous cells in a whorled pattern.Overlying the tumor, there is extensive vertically oriented hyperkeratosis and parakeratosis. The dermis contains chronic inflammatory infiltrate with melanin pigment.
Case contributed by Dr Mithilesh Chandra
Aneurysmal dermatofibroma
Aneurysmal dermatofibroma is a distinct clinicopathological variant of dermatofibroma. Clinically it presents as a bluish-black papule or nodule on the limbs of young to middle-aged adults. It may be associated with pain or rapid growth due to spontaneous hemorrhage.
On biopsy, the epidermis is acanthotic with basal layer hyperpigmentation. A subepidermal grenz zone is present. Dermis shows a relatively circumscribed tumor composed of spindle shaped fibroblasts and epithelioid histiocytes arranged in a storiform pattern. There are large areas of hemorrhage and multiple blood filled spaces varying from narrow clefts to large cavernous-like pseudovascular spaces not lined by endothelial cells. Prominent hemosiderin deposits, both intracellular and extracellular are also noted. Collagen trapping is seen at the periphery of the lesion. The tumor is also extending into subcutaneous fat.
Differential diagnoses include spindle cell hemangioendothelioma, Kaposi sarcoma and angiosarcoma. Spindle cell hemangioendothelioma is composed of true cavernous vascular spaces, papillary intraluminal structures and solid spindle cell areas. Kaposi sarcoma demonstrates slit-like blood-filled spaces formed by spindle endothelial cells with minimal atypia, hemorrhage and plasma cells. Angiosarcoma shows atypical plump endothelial cells with frequent mitoses and multilayering that dissect the collagen bundles.
Case contributed by Dr Mithilesh Chandra
Porphyria cutanea tarda
Porphyria cutanea tarda is the commonest of all porphyrias characterized by fragility and blistering of sun-exposed skin. It is usually acquired and does not cause acute attacks. It results from deficiency of the enzyme uroporphyrinogen decarboxylase.
On biopsy, it shows a cell-poor subepidermal blister with hardly any inflammation. There is preservation of dermal papillae in the floor of the bulla- termed as "festooning". Hyaline material (PAS positive and diastase resistant) is deposited in the dermal blood vessels.
Differential diagnoses include other examples of cell-poor subepidermal blister such as pseudoporphyria, epidermolysis bullosa (inherited), epidermolysis bullosa acquisita (non-inflammatory type) and cell-poor bullous pemphigoid.
Case contributed by Dr Mithilesh Chandra
Proliferating trichilemmal cyst
Proliferating trichilemmal cyst or tumor arises from the isthmic region of the hair follicle, often in a pre-existing trichilemmal cyst. It commonly presents as a rapidly growing nodule on the scalp.
On biopsy, the cyst is lined by stratified squamous epithelium showing trichilemmal keratinization without keratohyaline granules and having proliferating papillary projections extending into the cavity. There is no atypia of cells. The keratin is compact at most places with areas of calcification.
Case contributed by Dr Mithilesh Chandra
Pityriasis lichenoides chronica
Pityriasis lichenoides chronica presents as reddish brown papules with adherent mica-like scales that resolve with hypopigmentation. The lesions are usually distributed on the trunk, thighs and arms.
On biopsy, the epidermis shows acanthosis, focal parakeratosis, spongiosis with exocytosis of lymphocytes and vacuolar degeneration of basal layer. There is superficial perivascular infiltrate of lympho-histiocytes in the dermis along with pigment incontinence and extravasated erythrocytes.
Case contributed by Dr Mithilesh Chandra
Microvenular hemangioma
Microvenular hemangioma is an uncommon benign vascular tumor that occurs on the trunk, extremities or head and neck of young adults and rarely children. It often presents as a solitary erythematous to violaceous nodule or plaque.
On biopsy, it is comprised of collection of thin-walled, often branching blood vessels with narrow lumens that dissect through collagen bundles and also infiltrate adnexal structures. The vessels are lined by a single layer of benign looking endothelial cells plumper than normal and a prominent pericyte layer. The collagen is sclerotic.
Differential diagnosis includes Kaposi sarcoma, which shows irregularly anastomosing vascular channels surrounding pre-existing vessels along with interlacing bundles of spindle cells and lymphoplasmacytic infiltrate. Nuclear pleomorphism is variable and mitotic figures may be seen.
Case contributed by Dr Mithilesh Chandra
Palisaded neutrophilic and granulomatous dermatitis
Palisaded neutrophilic and granulomatous dermatitis (PNGD) presents as erythematous papules or plaques with crusting or central umbilication distributed mainly on the extensors of the extremities. Reactive granulomatous dermatitis is a recently proposed unifying term that encompasses PNGD, interstitial granulomatous dermatitis and interstitial granulomatous drug reaction, with overlapping clinical and histological features and similar systemic associations.
On biopsy, epidermis shows acanthosis. There is mixed dermal infiltrate with abundant neutrophils, karyorrhectic debris and some eosinophils along with palisading histiocytes surrounding areas of degenerated collagen. Foci of fibrinoid necrosis are present but there is no frank vasculitis or mucin deposition.
Case contributed by Dr Mithilesh Chandra
Syringocystadenocarcinoma papilliferum in situ
Syringocystadenocarcinoma papilliferum in situ (SCACPIS) is a rare cutaneous tumor of apocrine origin that usually arises in a pre-existing lesion of syringocystadenoma papilliferum (SCAP). It commonly presents on the scalp. A multi-step progression from nevus sebaceous to invasive syringocystadenocarcinoma papilliferum (SCACP) with intermediate stages of SCAP and SCACPIS has been proposed.
On biopsy, it shows verrucous epidermal hyperplasia with hyperkeratosis and hypergranulosis. Epidermal invaginations lined by a double cell layer are seen projecting into the dermis. The inner layer is composed of columnar cells with decapitation and the outer layer is of cuboidal cells with papillary projections and vascular plasma cell rich stroma. Several foci are showing papillary projections lined by multilayered epithelium with atypical cells and few mitotic figures. The overlying squamous epithelium is also showing marked atypia. However, no evidence of dermal invasion is seen.
Case contributed by Dr Mithilesh Chandra
Seborrheic inclusion cyst
Seborrheic inclusion cyst is a rare variant of epidermoid cyst that shows seborrheic keratosis-like changes in the cyst wall.
On biopsy, it shows epidermoid cyst lined with mature squamous epithelium with granular layer and laminated keratin. There are multiple areas of epithelial proliferation in the cyst lining. These cells are predominantly basaloid in nature with areas of squamous differentiation. Multiple pseudohorn cysts are seen. There is no atypia of cells.
Case contributed by Dr Mithilesh Chandra
Warty dyskeratoma
Warty dyskeratoma usually presents as a solitary papule or nodule with an umbilicated centre on the head and neck.
On biopsy, it shows a cup-shaped invagination extending into the dermis. The central depression is filled with keratinous plug. The underlying epidermis shows suprabasal clefting with numerous acantholytic and dyskeratotic cells in the cleft. Villi or dermal papillae covered by single layer of basal cells can be seen protruding into the cleft.
Case contributed by Dr Mithilesh Chandra
Reactive perforating collagenosis
Reactive perforating collagenosis (RPC) presents as pruritic skin-colored umbilicated papules with central keratotic plug distributed on the extensors of extremities and the face. It is characterized by transepidermal elimination of altered collagen. On biopsy, the central plug is composed of parakeratotic debris, degenerate collagen and inflammatory cells. The epidermis deep to the plug is thinned and traversed focally by vertically oriented collagen fibers. On either side of the cup-shaped deformity, the epidermis is hyperkeratotic and acanthotic. The superficial dermis shows neutrophils and lymphohistiocytes.
Case contributed by Dr Mithilesh Chandra
Xanthelasma palpebrarum
Xanthelasma palpebrarum is a type of planar xanthoma characterized by yellowish plaques on the eyelids. Lipid levels are normal in 50% of the patients. On biopsy, there are small aggregates of foam cells in the upper dermis. There is no fibrosis and no other inflammatory cells present.
Case contributed by Dr Mithilesh Chandra
Necrotic erythema nodosum leprosum
Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that may complicate the course of multibacillary leprosy. It generally occurs during anti-leprosy treatment and presents with multiple evanescent tender nodules associated with constitutional symptoms. Some of the clinical variants include pustular, bullous, ulcerative/ necrotic, erythema multiforme-like and haemorrhagic forms.
On biopsy, the epidermis is focally ulcerated with neutrophilic microabscesses in the stratum spinosum. There is papillary dermal edema and moderate to dense infiltrate of neutrophils admixed with foamy histiocytes and lymphocytes throughout the dermis with some spillover in the fat lobules. The blood vessels show neutrophils infiltrating into their walls, fibrinoid necrosis, endothelial swelling and red blood cell extravasation.
Differential diagnosis includes Sweet's syndrome, which lacks foamy histiocytes and true vasculitis, though dilated blood vessels and endothelial swelling may be noted.
Case contributed by Dr Divya Kannan and Dr Sudheer Arava
Inflammatory linear verrucous epidermal nevus (ILVEN)
ILVEN presents as linear intensely pruritic hyperkeratotic erythematous papules that coalesce to form plaques along the lines of Blaschko, usually in the first few years of life.
On biopsy, there are sharply demarcated alternating zones of orthohyperkeratosis and parakeratosis in a horizontal direction overlying psoriasiform hyperplasia of the epidermis. The granular layer is absent beneath the parakeratotic zones and thickened beneath the orthokeratotic zones of hyperkeratosis. The rete ridges are elongated and thickened. Mild spongiosis is also present. Upper dermis shows moderate perivascular lymphocytic infiltrate.
Differential diagnosis includes linear psoriasis, which shows confluent parakeratosis and thinned rete ridges.
Case contributed by Dr Mithilesh Chandra
Composite tumor composed of syringocystadenoma papilliferum and tubular apocrine adenoma
Composite or complex adnexal tumors exhibit histological features of two or three different tumours in a single cutaneous lesion. Syringocystadenoma papilliferum (SCAP) and tubular apocrine adenoma (TAA) are benign apocrine tumours that may coexist, often in a background of nevus sebaceous.
On biopsy, the tumor in the upper portion shows acanthotic epidermis giving rise to cystic invaginations lined by double-layered epithelium, composed of inner columnar cells showing decapitation secretion and outer cuboidal cells. The cystic spaces contain papillary projections and the stroma is rich in plasma cells. In the lower portion, there are round to oval shaped tubules lined by double-layered or multilayered epithelium in a paucicellular dense stroma. The inner layer comprises of cuboidal cells showing decapitation and the outer layer is of flattened myoepithelial cells. Overall histological features are suggestive of SCAP in the upper part and TAA in the lower part of the lesion.
Case contributed by Dr Divya Kannan and Dr Sudheer Arava
Verruciform xanthoma
Verruciform xanthoma presents as an asymptomatic, usually solitary warty plaque in the oral cavity, vulva, scrotum, penis and perianal skin.
On biopsy, it has verruca- like appearance on low magnification. It shows marked hyperkeratosis, parakeratosis with rounded rather than flattened nuclei and acanthosis. There is prominent exocytosis of neutrophils in the upper layers of epidermis and parakeratotic scale. The papillary dermis contains numerous foamy histiocytes with variable infiltrate of lymphocytes, plasma cells, neutrophils and eosinophils. It is better termed as xanthomatous verrucous acanthoma.
Case contributed by Dr Mithilesh Chandra
Pityriasis rubra pilaris
Pityriasis rubra pilaris (PRP) is a papulosquamous dermatosis characterised by erythematous hyperkeratotic perifollicular papules which coalesce into plaques. Typically islands of sparing are present.
On biopsy, it shows hyperkeratosis with follicular plugging. There is alternating orthokeratosis and parakeratosis in both horizontal and vertical directions forming a checkerboard pattern. Epidermis exhibits psoriasiform hyperplasia with broad rete ridges and thick suprapapillary plates and focal hypergranulosis. Mild perivascular lymphocytic inflammation is present in the superficial dermis.
PRP requires distinction from psoriasis which it can mimic both clinically and histopathologically. Features favouring psoriasis include confluent parakeratosis, presence of neutrophils forming Munro's microabscesses and spongiform pustule of Kogoj, hypogranulosis, elongated rete ridges with thinning of suprapapillary plates and tortuous congested vessels in the dermal papillae.
Case contributed by Dr Mithilesh Chandra
Granular cell tumor
Granular cell tumor is of neural derivation. It is usually solitary, smaller than 3 cm, and located in the dermis or subcutis and less frequently in the submucosa, smooth muscle, or striated muscle. It is also found in the internal organs, particularly in the upper aerodigestive tract. Multiple tumors occur in 10% of cases, either as an isolated condition or associated with Noonan and LEOPARD syndrome. Benign and malignant counterparts are known; the latter are rare, comprising fewer than 2% of all granular cell tumors. Most patients are middle-aged, with a peak incidence in the fourth to sixth decade of life. A slight female predominance exists. It is firm and round but with rather indefinite margins and sessile or pedunculated.
On biopsy, the tumor is composed of irregularly arranged sheets and nests of large polyhedral cells with a small central vesicular nucleus and abundant fine to coarsely granular eosinophilic cytoplasm. Large cytoplasmic globules surrounded by a clear halo (pustulo-ovoid bodies of Milian) are present. When these are extruded from cells and phagocytosed by histiocytes, they are termed angulate bodies. The cytoplasmic granules are PAS positive and diastase resistant. Cells infiltrate between collagen bundles and displace them. They surround the appendages and may extend into the arrector pili muscle. The tumor usually expresses S100 protein.
Case contributed by Dr Mithilesh Chandra
Dermal nerve sheath myxoma
Nerve sheath myxoma is a rare benign tumor derived from Schwann cells of peripheral nerves. It presents as a slow growing soft painless nodule on the limbs in young adults.
On biopsy, it is a well-circumscribed dermal tumor with multilobulated growth pattern. The lobules separated by delicate fibrous septae contain spindle, stellate to round cells lying in abundant myxoid stroma. The cells have scant eosinophilic cytoplasm with thin bipolar or multipolar processes. There is no nuclear atypia or mitotic figures. The tumor cells are strongly positive for S-100 protein on immunohistochemistry.
Differential diagnosis includes neurothekeoma, which is a multinodular benign tumor composed of epithelioid to slightly spindle cells. It has several variants- cellular, myxoid and mixed. It is characteristically S-100 negative and is therefore regarded as a distinct entity from nerve sheath myxoma.
Case contributed by Dr Mithilesh Chandra
Chondroid syringoma
Chondroid syringoma or cutaneous mixed tumor is a benign tumor of the sweat glands. Morphologically it is identical to pleomorphic adenoma / benign mixed tumor of the salivary gland. It is most often seen in middle aged men, commonly on the nose, followed by cheek and upper lip.
On biopsy, it shows a well circumscribed, lobulated mass centered in deep dermis or subcutaneous fat, with a prominent chondroid or myxoid stroma enveloping benign bland appearing epithelial and myoepithelial cells that form secondary structures which include glands and ducts, cysts, reticular lace-like network, keratinous cysts and foci of squamous differentiation. Other cells present include plasmacytoid, low cuboidal, spindle, clear cell, cells with follicular, pilomatrical differentiation and mature adipocytes. Though typically chondromyxoid, the background may be focally hyaline. Calcification / ossification may occur. Mitoses are sparse, necrosis is absent.
Case contributed by Dr Mithilesh Chandra
Glomus tumor
Glomus tumor occurs as a solitary bluish-purple painful nodule on the extremities, mainly on the fingers and toes in adults. Glomuvenous malformation or glomangioma is an inherited vascular anomaly that may present as multifocal bluish lesions or as solitary plaque.
On biopsy, it shows well-circumscribed encapsulated tumor in the lower dermis extending to the subcutis. The tumor is composed of sheets of glomus cells out of proportion to surrounding few blood vessels. Glomus cells are round monomorphic cuboidal cells with eosinophilic cytoplasm and darkly staining round to oval central nuclei. Tumor cells and vessels are embedded in fibrous stroma.
Glomangioma is characterized by enlarged and convoluted vascular channels and thin layers of glomus cells. Glomangiomyoma, in addition, shows prominent smooth muscle cells.
Case contributed by Dr Shruti Sharma
Digital papillary adenocarcinoma
Digital papillary adenocarcinoma is an aggressive tumor of the eccrine sweat glands often located on the distal extremities, particularly fingers or toes. It presents as a slow growing painless mass.
On biopsy, it showed flattened epidermis, grenz zone and a poorly circumscribed tumor filling the dermis. The tumor was composed of multiple variably dilated and interconnected duct like structures characteristically lined by two cell layers: inner lined by cuboidal to columnar cells and outer myoepithelial cells. Focal areas of multi-layering and papillary infoldings, mild to moderate atypia and frequent mitotic figures were seen.
Immunohistochemistry revealed diffuse positivity for pancytokeratin and S-100 in the tumor cells and smooth muscle actin in myoepithelial cells. There was a high proliferative activity with proliferation index of approximately 40% with Ki- 67.
Differential diagnoses comprise of tubular papillary adenoma, apocrine cystadenoma, microcystic adnexal carcinoma, hidradenoma and hidradenocarcinoma with glandular differentiation and areas of micropapillary growth.
Case contributed by Dr Mithilesh Chandra
Hailey-Hailey disease
Hailey-Hailey disease is an autosomal dominant disorder of keratinocyte adhesion, characterized by blisters and erosions most prominently in the flexures and sites of friction.
On biopsy, it shows hyperkeratosis, parakeratosis, crust formation and acanthosis. There are foci of broad suprabasilar clefting with numerous acantholytic cells lining the clefts and lying within them. Typically the acantholysis is incomplete, with cells retaining their connections, giving a 'dilapidated brick wall' appearance. Dyskeratosis is minimal. The adnexal epithelium is spared.
Differential diagnoses include Hailey-Hailey variant of Grover's disease, which has only a narrow vesicle involving no more than a few rete ridges, in contrast to the broad lesions of Hailey-Hailey disease. Pemphigus vulgaris is distinguished by less degree of acantholysis, involvement of adnexal structures and positive immunofluorescence. Darier's disease shows prominent dyskeratotic cells in the form of corps ronds and grains but less marked acantholysis.
Case contributed by Dr Mithilesh Chandra
Keratoacanthoma
Keratoacanthoma is a rapidly evolving skin tumor recently reclassified as well-differentiated squamous cell carcinoma. It occurs as a firm round skin-coloured or reddish nodule with a central horny plug on the centrofacial area. It typically resolves spontaneously.
On biopsy, it is an exo-endophytic lesion with an invaginating mass of keratinizing well-differentiated squamous epithelium at the bottom and sides. The central keratin filled crater enlarges as the lesion evolves. Peripheral epidermal lipping is also seen. The proliferating keratinocytes in the lower layers show mild atypia and mature towards the centre. The mature cells have abundant eosinophilic glassy cytoplasm. There is mixed inflammatory infiltrate in the surrounding dermis. The tumor does not extend beyond the level of the sweat glands.
Case contributed by Dr Mithilesh Chandra
Leiomyosarcoma
Cutaneous leiomyosarcoma is a rare smooth muscle tumor that may arise in the dermis or subcutaneous tissue and shows a predilection for extensor surfaces of the extremities.
On biopsy, the epidermis is thinned out with flattening of the rete ridges. The dermis shows a cellular lesion composed of plump spindle-shaped cells arranged in interlacing fascicles and having cigar-shaped nuclei with blunt ends and fibrillary eosinophilic cytoplasm. Mitotic figures are also seen. The tumor cells were positive for smooth muscle actin.
Differential diagnoses include other spindle cell tumors including spindle cell carcinoma, desmoplastic melanoma, dermatofibrosarcoma protuberans, fibrosarcoma, atypical fibroxanthoma and malignant peripheral nerve sheath tumor, which can be ruled out using a panel of immunohistochemical markers.
Case contributed by Dr Mithilesh Chandra
Follicular hybrid cyst
Follicular hybrid cyst arises from the combination of various parts of the pilosebaceous unit: infundibulum, isthmus and inferior portion. The most frequent combination described is that of infundibular and trichilemmal cysts, with predominant distribution on the head and neck region. The other combinations include infundibular cyst with pilomatricoma, trichilemmal cyst with pilomatricoma and eruptive vellus hair cyst with steatocystoma. Lichenoid interface dermatitis in the lining of follicular cysts is uncommon. It may be focal or diffuse, often in the absence of lichenoid inflammation of the overlying epidermis.
On biopsy, the uppermost portion of the cyst shows well-formed granular layer and loosely laminated keratin consistent with infundibular cyst, with sharp transition to the lower portion composed of large pale staining keratinocytes, absence of granular layer and compact keratin, suggestive of trichilemmal cyst. There is vacuolar degeneration of the basal layer of the cyst epithelium, numerous colloid bodies and lichenoid infiltrate.
Case contributed by Dr Mithilesh Chandra
Sebaceoma
Sebaceoma presents as a solitary skin-colored or yellowish nodule on the head and neck in the elderly.
On biopsy, it is a well-circumscribed uni- or multilobular tumor with smooth borders, which may extend to the deep dermis. The tumor comprises of nodules of immature germinative cells (>50% of the tumor cells) that have basaloid cytoplasm, central vesicular nuclei and occasionally contain lipid vacuoles. The criteria of 50% is not strict and is used to differentiate it from sebaceous adenoma. More mature and well-differentiated vacuolated sebocytes are noted focally. Though there can be mild atypia, necrosis and atypical mitosis are absent.
Sebaceous carcinoma is distinguished from sebaceoma by infiltrative growth pattern, tumor necrosis, cytological atypia, nuclear pleomorphism and atypical mitosis. Other differentials include basaloid tumors like trichoblastoma and basal cell carcinoma. Basal cell carcinoma shows apoptotic cells, peripheral palisading, peritumoral clefting and stromal mucin.
Case contributed by Dr Mithilesh Chandra
Proliferating trichilemmal tumor
Proliferating trichilemmal tumor arises from the isthmic region of the hair follicle, often in a pre-existent trichilemmal cyst. It presents as a rapidly growing large nodule commonly on the scalp.
On biopsy, it shows a well-circumscribed lobular proliferation of squamous cells with some peripheral palisading. There are central areas of trichilemmal keratinization, which correspond to abrupt transition from stratum spinosum to stratum corneum with no intervening granular layer. The tumor may be solid or solid-cystic. Vacuolated cells, focal necrosis, mild cellular atypia and squamous eddies may also be present. Malignant change is rare and is characterized by extensive cellular atypia and invasion of adjacent structures.
Case contributed by Dr Mithilesh Chandra
Piloleiomyoma
Piloleiomyoma is a benign tumor of smooth muscle derived from the arrector pili muscle. It generally presents as multiple firm reddish-brown painful nodules on the extremities and trunk.
On biopsy, it is a circumscribed non-encapsulated dermal tumor with an overlying uninvolved grenz zone of papillary dermis. The tumor is composed of bundles of smooth muscle arranged in interlacing and whorled pattern. The cells have abundant eosinophilic cytoplasm and elongated nuclei with blunt ends. There is no nuclear atypia or mitotic activity.
Differential diagnoses include smooth muscle hamartoma, which shows discrete bundles of smooth muscle oriented in various directions with collagen interspersed between the smooth muscle bundles. In angioleiomyoma, interlacing smooth muscle bundles are present between numerous vascular channels which are thick walled and merge with the fascicles.
Case contributed by Dr Mithilesh Chandra
Morpheaform basal cell carcinoma
Morpheaform basal cell carcinoma (BCC) accounts for 5% of all BCCs. It classically presents as a pink to ivory-white shiny smooth indurated plaque with ill-defined borders. Ulceration is uncommon and very superficial when it occurs. It is an aggressive subtype with high recurrence rates.
On biopsy, it is poorly circumscribed and composed of thin strands and nests of basaloid cells with limited peripheral palisading and retraction artifacts. The surrounding stroma is dense and sclerotic. Widespread invasion into the reticular dermis and subcutaneous fat is seen.
Differential diagnoses include desmoplastic trichoepithelioma and microcystic adnexal carcinoma. Desmoplastic trichoepithelioma differs from morpheaform BCC by its symmetry and keratin horn cyst formation and absence of peripheral palisading, necrosis, retraction artifact and mitotic activity. CK20 positive Merkel cells are identified in most desmoplastic trichoepitheliomas but only in a small percentage of BCCs. Microcystic adnexal carcinoma is poorly circumscribed and deeply infiltrating. It can be distinguished from morpheaform BCC based on ductal differentiation and intracytoplasmic lumen formation.
Case contributed by Dr Mithilesh Chandra
Sebaceous carcinoma
Sebaceous carcinoma is a malignant tumor with sebaceous differentiation that is usually seen in elderly individuals. It is divided into periocular and extraocular subtypes. The tumor presents as a rapidly enlarging yellowish to pink papule or nodule that may show ulceration. Lesions occurring outside the head and neck region are strongly associated with Muir-Torre syndrome.
On biopsy, the epidermis is ulcerated. The tumor is connected to the overlying epidermis and is arranged as lobules separated by fibrovascular stroma. It is composed of admixture of predominant population of atypical basaloid cells with vesicular nuclei and prominent nucleoli and sparsely distributed mature sebocytes with vacuolated cytoplasm. There is marked cytological atypia, frequent mitoses and areas of necrosis. Tumor cells are seen infiltrating into the deeper dermis. There is dense chronic inflammatory infiltrate comprising of lymphocytes, plasma cells and few eosinophils.
Sebaceous carcinoma is differentiated from sebaceous adenoma and sebaceoma by presence of infiltrative margins, cytological and nuclear atypia, numerous atypical mitoses and necrosis. Another differential includes basal cell carcinoma with sebaceous differentiation, which will show basaloid cells with peripheral palisading, retraction artefacts, myxoid stroma and focal differentiation towards mature sebocytes.
Case contributed by Dr Mithilesh Chandra
Re-epithelialized subepidermal blister with eosinophils, likely to be bullous pemphigoid.
The diagnosis can be confirmed on direct immunofluorescence (DIF)
Bullous pemphigoid is an autoimmune vesiculobullous disease that characteristically shows a subepidermal blister with eosinophils. However, there can be histological variations that can produce diagnostic confusion. One of these is bullous pemphigoid presenting as an intraepidermal blister. This occurs due to re-epithelialization that starts as early as 48 hours after wound formation at the blister edge. As the blisters in bullous pemphigoid are tense and last for a long time, a pseudointraepidermal cleft is formed due to epidermal reparative process. Therefore, blisters less than 48 hours old should be biopsied to accurately identify the plane of cleavage. The clue in identifying re-epithelialization is that the keratinocytes of the spinous layer are arranged parallel to the skin surface rather than being vertically oriented beneath a true intraepidermal blister. Recuts are helpful in showing foci of subepidermal clefting. Presence of numerous eosinophils in the blister cavity and within the papillary dermis favour the diagnosis of bullous pemphigoid.
Diagnosis of bullous pemphigoid can be confirmed on DIF, which demonstrates linear deposits of IgG and/ or C3 at dermo-epidermal junction. Other tests that can be done are IIF on human salt split skin, BP180 and BP 230 ELISA and immunoblot, depending on their availability.
Differential diagnosis includes pemphigus vulgaris, which shows an intraepidermal blister with acantholytic cells, latter finding was absent in this case.
Case contributed by Dr Mithilesh Chandra
Angiosarcoma
Angiosarcoma is a malignant vascular tumor that usually occurs in three settings: idiopathic on the head and neck in the elderly males, associated with chronic lymphedema, and post-irradiation. Presentation in children as in this case is extremely uncommon and has been associated with xeroderma pigmentosum, Aicardi syndrome and radiation therapy. Clinically, it presents as rapidly growing dusky blue or red nodules or even hemorrhagic blisters. Pediatric tumors differ from those in adults in that they are more common in females, occur on the lower extremity and tend to be small and unifocal.
On biopsy, it is a poorly circumscribed dermal tumor with infiltration into the subcutaneous fat. Both angiomatous and solid areas are seen. In the angiomatous areas, irregular anastomosing vascular channels dissect between the collagen bundles and around appendages. These vascular channels are lined by crowded, plump, atypical endothelial cells with enlarged hyperchromatic nuclei and prominent nucleoli. Epithelioid morphology of tumor cells is prominent, which distinguishes pediatric angiosarcoma from the adult form. Atypical mitotic figures and focal areas of hemorrhage are also noted.
Case contributed by Dr. Mithilesh Chandra
Trichotillomania
Trichotillomania is an impulse control disorder characterized by compulsive hair pulling which results in a sense of relief. It occurs in two forms: in children as a habit akin to nail biting and in adult women with some form of psychological stress. It produces a bizarre pattern of incomplete hair loss with hair broken at various distances from clinically normal scalp of crown and occipital regions. Other hair bearing sites like eyebrows, eyelashes may also be affected.
On biopsy, there are an increased number of catagen hairs showing apoptotic keratinocytes. Dilated follicular infundibula contain pigmented casts and keratin plugs. Some hair follicles appear small and distorted with irregular thickness (trichomalacia). There is only minimal perifollicular inflammation.
Differential diagnosis includes alopecia areata, which shows telogen follicles, small anagen follicles, prominent peribulbar inflammatory infiltrate and some pigment casts.
Case contributed by Dr. Mithilesh Chandra
Secondary syphilis, granulomatous
Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis, and is usually associated with tertiary stage disease. Clinically, it presents commonly as reddish-brown papules and nodules or may be seen as an evolutionary histopathologic change in older lesions (more than 4 weeks duration) of varied initial presentation. There is frequent sparing of the palms and soles in this variant.
On biopsy, the epidermis is focally ulcerated with ulcer bed showing dense neutrophilic infiltrate. There are epithelioid cell granulomas along with increased numbers of plasma cells and lymphocytes in the superficial and deep dermis. The inflammatory infiltrate is arranged in a T-shape pattern with close apposition to dermo-epidermal junction along the papillary dermal vessels and extends into the reticular dermis along adnexal structures. Vascular proliferation and endothelial cell swelling are noted. Palisading granulomas as seen in granuloma annulare, perineural granulomas resembling leprosy and sarcoidal granulomas are rarely described. As Warthin-Starry stain is often negative in these cases, immunoperoxidase staining to demonstrate Treponema pallidum should be performed as it is more sensitive and also to be correlated with serologic studies.
Case contributed by Dr. Mithilesh Chandra
Rheumatoid nodule
Rheumatoid nodules occur as asymptomatic, firm, dome-shaped, skin colored nodules on the extensor aspect of forearms and elbows, knuckles, knees and feet. They are common in patients with severe rheumatoid arthritis and are associated with a high titer of rheumatoid factor. Accelerated rheumatoid nodulosis is characterized by rapid onset of painful rheumatoid-like nodules on the hands and feet in association with methotrexate therapy.
On biopsy, changes arelocated in the subcutaneous fat and deep dermis. There are central areas of collagen degeneration admixed with fibrinoid material, which appear intensely eosinophilic and amorphous. Necrobiotic foci are surrounded by a palisade of histiocytes, occasional giant cells, lymphocytes, neutrophils and plasma cells (red granulomas). The stroma shows proliferation of blood vessels. Long standing cases demonstrate fibrosis and cystic degeneration.
Differential diagnosis is subcutaneous granuloma annulare, which shows foci of degenerate collagen with mucin deposition and therefore appears basophilic (blue granulomas). Surrounding the degenerated foci are histiocytic palisades. Stromal fibrosis and fibrin are uncommon.
Case contributed by Dr. Mithilesh Chandra
Hidradenoma papilliferum
Hidradenoma papilliferum is a benign adnexal tumor that originates from apocrine sweat glands of anogenital region in middle-aged females. Rarely, ectopic forms have been described, as in this case, particularly on the head and neck, the eyelid and external ear, where modified apocrine glands are found normally. The tumor presents as a slow-growing asymptomatic erythematous papule or nodule.
On biopsy, the epidermis is ulcerated. The tumor forms a well-demarcated nodule in the dermis comprising of papillary processes with arborizing trabecular pattern, that project into cystic spaces. The epithelial lining is double layered, composed of inner myoepithelial cells and outer tall columnar cells, showing decapitation secretion. Larger fronds have a fibrous core.
Differential diagnoses include syringocystadenoma papilliferum and tubular apocrine adenoma. Syringocystadenoma papilliferum appears as an invagination from the overlying epidermis into the underlying dermis. The papillae are lined by hyperplastic stratified squamous epithelium superficially and double layered lining with decapitation in the deeper parts. The fibrovascular cores of papillary processes contain abundant plasma cells. Tubular apocrine adenoma is composed of lobules of tubular structures, which have inner lining of cells showing decapitation and outer cuboidal cells. The stroma consists of fibrous tissue with hardly any inflammatory cells.
Case contributed by Dr. Mithilesh Chandra
Oral histoplasmosis
Histoplasmosis mostly occurs as an asymptomatic pulmonary infection in immunocompetent individuals, with primary mucocutaneous disease being uncommon. Oral involvement in histoplasmosis is seen in two-thirds of patients with disseminated disease, particularly in severely immunosuppressed patients such as those with advanced HIV infection, and may be the initial manifestation of systemic disease. Very rarely oral lesions may be the only presenting feature. It can affect any site in the oral cavity, common ones include tongue, hard and soft palate, gingiva, and buccal mucosa. Oral lesions can present as nodules, plaques, ulcers, or fungating growth. Differential diagnoses include tuberculosis, syphilis, mucosal leishmaniasis and squamous cell carcinoma.
On biopsy, there is dense diffuse inflammatory infiltrate composed of histiocytes, lymphocytes, and few plasma cells in the lamina propria. Numerous 2–4 µm sized round to oval yeasts surrounded by a characteristic halo are seen predominantly within the cytoplasm of histiocytes and some extracellularly. The organisms were highlighted with Periodic Acid-Schiff stain.
Although of identical size, Leishman-Donovan bodies demonstrate a rounded structure, the nucleus and a smaller darker bar-like structure, the kinetoplast, overall morphology resembling a diya.
Case contributed by Dr. Mithilesh Chandra
Aneurysmal dermatofibroma
Aneurysmal dermatofibroma is a distinct clinicopathological variant of dermatofibroma. Clinically it presents as a bluish-black papule or nodule on the limbs of young to middle-aged adults. It may be associated with pain or rapid growth due to spontaneous hemorrhage. Local recurrence is seen in 19% of the cases.
On biopsy, epidermis is acanthotic with basal layer hyperpigmentation. A subepidermal grenz zone is present, beneath which there are multiple blood filled spaces varying from narrow clefts to large cavernous-like pseudovascular spaces which are not lined by endothelial cells. The vascular channels are surrounded by histiocytes which contain hemosiderin, foam cells and fibroblasts. Solid areas with usual morphology of dermatofibroma are invariably present.
Differential diagnoses include spindle cell hemangioendothelioma, Kaposi sarcoma and angiosarcoma. Spindle cell hemangioendothelioma is composed of true cavernous vascular spaces, papillary intraluminal structures and solid spindle cell areas. Kaposi sarcoma demonstrates slit-like blood-filled spaces formed by spindle endothelial cells with minimal atypia, hemorrhage and plasma cells. Angiosarcoma shows atypical plump endothelial cells with frequent mitoses and multilayering that dissect the collagen bundles.
Case contributed by Dr. Mithilesh Chandra
Superficial acral fibromyxoma
Superficial acral fibromyxoma is a benign soft tissue neoplasm with predilection for subungual or periungual regions of fingers and toes. It occurs in young to middle-aged adults as a small slow growing usually asymptomatic nodule.
On biopsy, it shows a well-circumscribed dermal tumor composed of bland proliferation of spindle and stellate shaped cells with random, loose storiform or fascicular growth patterns. The cells are embedded within a myxoid or myxo-collagenous stroma, often with prominent small vascular channels and increased mast cells. Mitotic figures are rare and mild nuclear atypia may be present. On IHC, tumor cells are positive for CD34, epithelial membrane antigen (EMA) and CD99. Histopathologic differential diagnoses include myxoid dermatofibrosarcoma protuberans (DFSP), low grade fibromyxoid sarcoma and nodular fasciitis.
Myxoid DFSP is distinguishable by retention of tight storiform architecture peripherally and in the subcutis, more infiltrative growth pattern and lack of reactivity for EMA. Low-grade fibromyxoid sarcoma is composed of monomorphic spindle cells without atypia in an alternating myxoid and collagenous stroma. IHC is non-specific except for MUC4 positivity. Nodular fasciitis reveals plump spindle cells in a loose myxoid to collagenous stroma, with a feathery appearance. Scattered lymphocytes, histiocytes, osteoclast type giant cells with areas of erythrocyte extravasation are often present. IHC shows diffuse positivity for smooth muscle actin.
Case contributed by Dr. Mithilesh Chandra
Apocrine hidrocystoma
Apocrine hidrocystoma represents cystic dilatation of apocrine glands. It presents as a solitary or occasionally multiple skin-colored to greyish-blue dome-shaped translucent nodules distributed lateral to the outer canthus of the eye. Multiple lesions may occur in Schopf-Schulz-Passarge syndrome. Clinically the lesions are indistinguishable from eccrine hidrocystomas. On biopsy, the cyst may be unilocular or multilocular with a lining of columnar epithelium and peripheral flattened layer of elongated myoepithelial cells. Characteristically, there is pinching off (decapitation) of the cytoplasm of luminal border of lining cells, typical of apocrine secretory activity, which differentiates it from eccrine hidrocystoma. The secretions in the cysts may be coagulated and stained using PAS stain.
Case contributed by Dr. Mithilesh Chandra
Tufted angioma
Tufted angioma is a benign vascular tumor that usually presents during infancy and childhood. Onset in adulthood is uncommon, with less than 10% of the cases developing after 5th decade. The clinical presentation is diverse, most often being a solitary dusky red to purplish ill-defined indurated plaque on the neck and upper trunk. It may sometimes be painful and associated with hyperhidrosis and hypertrichosis. Linear, annular, multifocal and eruptive variants are less common. On biopsy, there are multiple well-circumscribed compact lobules throughout the dermis, which are composed of tightly packed capillaries with oval to spindle shaped cells, giving a characteristic cannonball appearance. Some lobules bulge into the dilated lymphatic channels at the periphery. There is no cellular atypia. It is differentiated from Kaposi sarcoma by the absence of interlacing sheets of spindle cells, slit-like irregular and jagged vascular spaces and inflammatory infiltrate rich in plasma cells.
Case contributed by Dr. Mithilesh Chandra
Nail lichen planus with foreign body granulomatous reaction to intramatricial triamcinolone acetonide injection
Intralesional triamcinolone acetonide injection is associated with early and delayed adverse effects. Early effects include pain, bruising, infection, bleeding, allergic contact dermatitis, impaired wound healing and sterile abscess. Delayed side-effects comprise of subcutaneous lipoatrophy, hypo or depigmentation, telangiectasias, hypertrichosis and acneiform eruption. Dermal deposition of triamcinolone with foreign body granulomatous reaction has been described in keloids, nodulocystic acne and alopecia areata. On biopsy, epidermis shows saw-toothing of rete ridges with focal interface dermatitis. Mid and deep dermis demonstrate nodular collections of histiocytes, foreign body type multinucleated giant cells and some lymphocytes. The cytoplasm of giant cells contains finely granular basophilic material and irregular clefts at places. The basophilic material is also present interstitially between the collagen fibers.
Case contributed by Dr. Mithilesh Chandra
Langerhans cell histiocytosis (LCH)
Skin is the second most commonly involved organ after bone in LCH, affecting 30-60% of the cases and being the only site involved in 10%. The most characteristic cutaneous lesion in children consists of papulosquamous lesions with greasy scales affecting the scalp and flexures, resembling seborrhoeic dermatitis. Other morphologies include nodules, vesicles, bullae, pustules, petechiae and purpura. Nails, oral and genital mucosa may also be involved. In adults, ulceration of the flexures and ano-genital region is common. On biopsy, there are clusters of large ovoid cells, 15–25 µm in diameter, with abundant eosinophilic cytoplasm and a nucleus which is indented or reniform and sometimes eccentric – ‘coffee-bean’ nucleus. These cells are found immediately beneath the epidermis and often assume a periappendageal distribution. Focally, the cells invade the epidermis, forming small aggregates. The inflammatory infiltrate in the dermis comprises of eosinophils, neutrophils, lymphocytes and multinucleated giant cells. Immunohistochemical markers for Langerhans cells include CD1a, S100 protein and langerin (CD207). Electron microscopy shows Birbeck granules, which are tennis racquet-shaped organelles.
Case contributed by Dr. Mithilesh Chandra
Secondary syphilis (granulomatous variant)
Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis. Clinically it presents commonly as reddish-brown papules and nodules or may be seen as an evolutionary histopathologic change in older lesions (more than 4 weeks duration) of varied initial presentation. There is frequent sparing of the palms and soles in this variant.
On biopsy, there are epithelioid cell granulomas along with increased numbers of plasma cells and lymphocytes in the superficial and deep dermis. The inflammatory infiltrate is often arranged in a T-shape pattern with close apposition to dermo-epidermal junction along the papillary dermal vessels and extending into the reticular dermis along adnexal structures. Vascular proliferation and endothelial swelling are common. Palisading granulomas as seen in granuloma annulare, perineural granulomas resembling leprosy and sarcoidal granulomas are rarely seen. Warthin-Starry stain is often negative in these cases; immunoperoxidase staining to demonstrate Treponema pallidum is more sensitive. The biopsy findings should be correlated with serologic studies.
Case contributed by Dr. Mithilesh Chandra
Eccrine poroma
Eccrine poroma is derived from intraepidermal portion of the eccrine duct, that is acrosyringium. Although traditionally considered as eccrine, some poromas may demonstrate apocrine differentiation. It presents as an erythematous moist exophytic nodule, usually on the palms and soles, though head and neck may sometimes be involved. Occasionally, lesions can be pigmented.
On biopsy, it is a circumscribed tumor composed of broad columns of uniform basaloid cuboidal cells extending into the dermis from the undersurface of the epidermis. The cells are smaller than and well delineated from the adjacent normal keratinocytes. They are PAS positive and diastase sensitive. Ducts and small cysts are seen within the tumor columns. The stroma is richly vascular with telangiectatic vessels. Melanin may be seen in pigmented lesions. Sebaceous and pilar differentiation may be noted in poromas of apocrine origin.
Case contributed by Dr. Manoj Singh and Dr. M. Ramam
Talon noir (intracorneal hemorrhage)
Talon noir or black heel presents as recent onset asymptomatic closely aggregated bluish-black macules on thenar eminence at the base of the thumb. It commonly occurs in golfers, weightlifters and tennis players, resulting from shear-stress rupture of papillary dermal capillaries. A similar presentation can also occur on the soles in athletes. Its importance lies in its resemblance to acral lentiginous melanoma or melanocytic nevus.
Dermoscopy shows homogenous reddish pigmented globules of hemorrhage, which may be arranged along the crests, giving a parallel appearance mimicking acral melanoma. Paring the affected area reveals blood in the stratum corneum and removes the pigment completely.
On biopsy, the findings are limited to the stratum corneum which shows intracorneal hemorrhage. Depending on how old the hemorrhage is, there can be extravasated red blood cells or amorphous yellow-orange stained material in rounded collections. This material is positive for benzidine, suggesting that it is derived from hemoglobin but negative for Perls' stain for hemosiderin.
Case contributed by Dr. Geeti Khullar and Dr. Shruti Sharma
Verrucous hemangioma
Verrucous hemangioma is a vascular malformation that develops at birth or in childhood and grows proportionately with age. The lesions predominantly occur on the lower limbs as linear bluish- red plaques or nodules that are initially soft and over time become verrucous. On biopsy, there is hyperkeratosis, irregular acanthosis and papillomatosis. Markedly dilated small and large vascular channels are present in the superficial and deep dermis and even the subcutaneous fat. The vessels may be thrombosed. Angiokeratoma is a close differential diagnosis characterized by similar epidermal findings and ectasia of superficial dermal vessels only.
Case contributed by Dr. Meenakshi Batrani
Extramammary Paget's disease, acantholytic type, with colonization of eccrine glands
Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. Extramammary Paget's disease (EMPD) is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, ulcerations and lichenification. Unlike mammary Paget’s disease, where 93-100% of cases are associated with underlying in-situ or invasive ductal carcinoma, the extramammary form is associated with an underlying in situ or invasive neoplasm in a much smaller proportion of cases. Approximately 25% of cases have a primary cutaneous adnexal carcinoma, mostly of apocrine type, but sometimes derived from periurethral, eccrine, perianal, or Bartholin's glands. An additional 10% to 15% of EMPD patients have an internal carcinoma involving the bladder, rectum, cervix, prostate, or urethra.
On biopsy, the tumor cells of EMPD (Paget’s cells) have abundant pale cytoplasm with a prominent, large vesicular nucleus. The vacuolated cytoplasm also stains with PAS, mucicarmine and Alcian blue. In most cases, the tumor cells are located in a nested and single-cell pattern, within the epidermis. Less common patterns observed are (i) glandular; (ii) acantholytic-like; (iii) upper nest; (iv) tall nest; (v) budding; and (vi) sheet-like. The tumor cells in the early lesions are arranged mainly in lower epidermis; later, the epithelium of the cutaneous adnexal structures and the entire thickness of the epidermis become involved. In the advanced stage, tumor cells can invade the dermis and may metastasize via the lymphatic system.
The main differential diagnostic considerations include melanoma and squamous cell carcinoma in situ (Bowen’s disease). The tumor cells of primary vulvar EMPD show immunoreactivity for low molecular weight keratins such as CK7, CEA, GCDFP, EMA, and negative for CK20 and CDX2, S-100 protein and HMB-45. Pagetoid Bowen’s disease is distinguished by expression of high molecular weight keratins, p16, and p63. Pagetoid melanoma is distinguished by expression of S-100 and HMB45. Vulvar Paget disease of colorectal origin expresses CK20, CDX2, and CEA; vulvar Paget disease of urothelial origin may express CK20, uroplakin, and thrombomodulin.
Case contributed by Dr. Meenakshi Batrani
Scabies
Multiple sections are sometimes required to find diagnostic intracorneal eggs, larvae, mites, mite parts, and excreta (scybala). Pink pigtails (egg fragments or castings) attached to the stratum corneum are also a useful clue of scabies infestation. The mite or mite parts are seen only if a burrow is biopsied, while in papulo-vesicular lesions, which are the most common presentation, the mite is not seen. Other features on histopathology include spongiosis and eosinophilic exocytosis, which are common to many arthropod bite reaction, but are suggestive of scabies in the relevant clinical setting, and should also prompt an examination of multiple step sections which increases the chances of finding the mite or its parts.