Answers to Image of the Month 2019
Case contributed by Dr. Mithilesh Chandra
Bowen's disease with secondary localized cutaneous amyloid
Bowen’s disease is a clinical expression of squamous cell carcinoma in situ of the skin. It presents as an asymptomatic well-defined erythematous scaly plaque, which expands centrifugally. Verrucous, nodular and pigmented variants occur. Though it has a predilection for sun-exposed areas, lesions may also develop on the trunk, vulva and nail bed.
On biopsy, it shows full-thickness involvement of the epidermis by atypical keratinocytes. This is associated with disorderly maturation of the epidermis, mitoses at different levels and dyskeratotic cells. There is loss of granular layer with overlying parakeratosis and hyperkeratosis. The papillary dermis in this case showed amorphous deposits of eosinophilic material, which demonstrated positive staining with Congo red. Secondary localized cutaneous amyloid can occur in various skin lesions of epithelial origin including basal cell carcinoma, Bowen's disease, squamous cell carcinoma, seborrheic keratosis, actinic keratosis and disseminated superficial actinic porokeratosis. It has been proposed that protein from apoptotic tumour cells is converted into amyloid in dermal fibroblasts or macrophages. Positive staining for cytokeratin 5 confirms the origin of amyloid from keratinocytes.
Case contributed by Dr. Shruti Sharma
Blue nevus
Blue nevus is usually a blue-black or deep blue, dome-shaped papule found most commonly on the extremities. Clinical variants include eruptive, agminate, plaque, target, amelanotic, linear, satellite, disseminated and familial forms. Excisional biopsy should be performed to rule out melanoma. On biopsy, it is composed of spindle‐shaped, dendritic melanocytes admixed with ovoid or fusiform, elongated melanocytes, located in the interstices of dermal collagen of the upper and mid-dermis. Nevus cells can extend into the lower dermis along appendages or in the perivascular and perineural areas. The dendritic melanocytes do not show significant mitotic activity or atypical cytology. An admixture of melanophages with intracytoplasmic coarse melanin granules, is often seen. Dendritic melanocytes stain positively for S-100, HMB‐45 and Melan- A. Histological variants include cellular, epithelioid and deep penetrating types.
Case contributed by Dr. Mithilesh Chandra
Pityriasis lichenoides et varioliformis acuta
Pityriasis lichenoides et varioliformis acuta develops in crops and appears polymorphic. Constitutional symptoms such as fever, malaise and arthralgia may precede or accompany the onset of lesions. Trunk, thighs and upper arms are mainly affected. The initial lesion is a pink papule that undergoes central vesiculation and haemorrhagic necrosis. Lesions heal with varioliform scarring. On biopsy, epidermis shows spongiosis and parakeratosis with neutrophilic crust. Interface dermatitis is prominent comprising of basal cell vacuolization and necrotic keratinocytes. Extensive epidermal necrosis is seen in severe ulcerative cases. Lymphocytes and erythrocytes extend into the epidermis. Dense wedge-shaped lymphocytic infiltrate is present upto the deep dermis. Endothelial swelling of blood vessels, extravasation of erythrocytes and occasionally fibrinoid necrosis are seen.
Case contributed by Dr. Mithilesh Chandra
Lucio phenomenon
Lucio phenomenon is a rare manifestation of lepra reaction seen in primitive, non-nodular form of diffuse lepromatous leprosy of Lucio and Latapi, commonly found in Mexico and Central America. Clinically it presents as purpuric lesions, hemorrhagic bullae and painful necrotic ulcers with irregular, jagged and angulated margins. Differentiation from necrotic erythema nodosum leprosum may be difficult, with reported cases of overlap between the two entities.
On biopsy, it shows an intraepidermal blister. There is endothelial cell proliferation, neutrophilic infiltrate and nuclear debris within and surrounding the vessel walls and marked red blood cell extravasation, features suggestive of leukocytoclastic vasculitis. Some of the vessels in the papillary dermis are thrombosed. There are sheets of foamy histiocytes present in the dermis. Modified Ziehl-Neelsen stain showed numerous acid fast bacilli in the endothelial cells.
Case contributed by Dr. Mithilesh Chandra
Erythema elevatum diutinum
Erythema elevatum diutinum (EED) presents in middle-aged adults as asymptomatic symmetrical reddish-brown plaques and nodules on the dorsa of hands, elbows, knees and Achilles tendons. Initially the lesions are soft, but eventually fibrose and heal with atrophic scars. It has been associated with autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease, infections like Streptococcus, HIV, hepatitis and IgA monoclonal gammopathy.
Biopsy findings vary with the age of the lesion. In early stage, the features are suggestive of leukocytoclastic vasculitis, characterized by perivascular infiltrate of neutrophils, endothelial swelling, fibrin deposits within and around the vessel walls. Few eosinophils are also present. In late lesions, there is fascicled proliferation of spindle cells producing angiocentric eosinophilic fibrosis. Capillary proliferation and infiltration of lymphocytes, histiocytes and plasma cells are also seen. Cholesterol deposits in histiocytes and in extracellular tissue, known as extracellular cholesterolosis may be present. It differs from granuloma faciale in the predominance of neutrophils rather than eosinophils and the involvement of the adventitial dermis, which is spared in granuloma faciale.
Case contributed by Dr. Geeti Khullar
Kaposi sarcoma
Kaposi sarcoma is a multifocal, endothelial proliferation of low grade malignant potential caused by human herpesvirus 8 (HHV‐8), most often with cutaneous involvement and with or without visceral extension. There are four distinct clinical subtypes: classic, endemic, iatrogenic and AIDS associated.
Biopsy findings parallel the clinical progression of patch, plaque and tumour stages. In the patch stage, there is a dermal proliferation of irregular, often jagged, vascular channels which partly surround pre-existing blood vessels. This characteristic appearance has been termed the ‘promontory sign’. The vascular proliferation is also present around appendages and between collagen bundles. The vessels are thin walled and lined by plump or inconspicuous endothelial cells. Perivascular lymphocytes and plasma cells may be present. Extravasated erythrocytes and deposits of hemosiderin are also found in the dermis. Nodules and plaques consist of interlacing bundles of spindle cells and intimately related, poorly defined slit-like vessels. The spindle-cells show variable nuclear pleomorphism. Mitotic figures are present, but not usually frequent. Clusters of eosinophilic hyaline globules which are PAS positive, may be seen within spindle cells and macrophages or in an extracellular location. Immunohistochemical studies have demonstrated the presence of CD31, CD34, D2-40 and HHV-8. HHV-8 is largely confined to the spindle cells in the nodular stage and the endothelial cells of slit-like vessels in the early patch stage.
Case contributed by Dr. Mithilesh Chandra
Sinusoidal hemangioma
Sinusoidal hemangioma is a rare benign cutaneous vascular tumor, regarded as a variant of cavernous hemangioma. It develops in adults, predominantly females, as an asymptomatic solitary erythematous to bluish nodule on the trunk or extremities.
On biopsy, the tumor is located in the deep dermis and subcutaneous tissue. It exhibits a lobular architecture, consisting of dilated, thin-walled blood vessels lined by a single layer of flattened endothelium. The intercommunicating vascular channels lie in back-to- back arrangement without much intervening stroma, producing a sinusoidal appearance. Pseudopapillary structures and focal pleomorphism of endothelial cells have been described. There is no mitotic activity. Long standing lesions may show hyalinized collagen, thrombosis, infarction, dystrophic calcification, metaplastic ossification and foamy macrophages. Histopathological differential diagnoses include lobular capillary hemangioma and tufted angioma.
Case contributed by Dr. Mithilesh Chandra
Clear cell hidradenoma
Clear cell hidradenoma, also known as nodular or solid-cystic hidradenoma is a benign sweat gland tumor that can show either eccrine or apocrine differentiation. It is predominately seen in females in the age group of 20-50 years. Clinically it presents as a slow-growing solitary nodule on the scalp, face, trunk and proximal limbs.
On biopsy, it is a well-circumscribed non-encapsulated multilobular dermal tumor that may show connection with the epidermis in about one-fourth of the cases. It is characterized by two types of cells in variable proportions: large round cells with clear cytoplasm and small dark nuclei and the other type of cells with finely granular eosinophilic cytoplasm and elongated nuclei. Clear cells contain glycogen and some PAS-positive, diastase-resistant material but no lipid. The tumor is composed of both solid and cystic components. Cystic spaces are lined by flat to cuboidal epithelium and contain homogenous eosinophilic material. Duct-like structures are often present. The stroma between the tumor lobules varies from thin vascularised cords of fibrous tissue to focally hyalinized collagen.
Case contributed by Dr. Mithilesh Chandra
Primary subcutaneous hydatid cyst
Hydatid disease is a zoonotic parasitic infestation caused by the larval stage of Echinococcus granulosus. Humans are the intermediate host and acquire the infection after ingestion of eggs in the contaminated food transmitted through feces of dogs or sheep. Liver and lungs are most commonly affected, although any organ may be involved including the subcutis. The prevalence of subcutaneous hydatid cyst ranges between 0.6% to 2.6%. It can be either primary, when the cyst is localized only to the subcutaneous tissue with no other foci of hydatidosis or secondary when in addition to the subcutaneous tissue, it is present in at least one of the extracutaneous sites like the lung, liver or spleen.
Primary subcutaneous hydatid cyst is rare and often poses a diagnostic challenge. It commonly manifests as a painless slowly enlarging mobile swelling on the thigh and gluteal region and infrequently in the head and neck area.
Fine needle aspiration cytology, though it can precipitate an anaphylactic reaction, may demonstrate remnants of laminated membrane, scolex or hooklets.
Radiological investigations such as ultrasound is preferred in making the diagnosis, while magnetic resonance imaging and computed tomography are useful in delineating the relationship of the cyst to the surrounding structures.
On biopsy, it shows three layers. The outer adventitial layer or pericyst consists of dense fibrovascular tissue. The middle lining of the cyst shows acellular, avascular, eosinophilic, refractile and chitinous laminated membrane, which is characteristic. The laminated membrane is produced by the inner germinal layer that has scolices. The outermost layer is infiltrated by lymphocytes, histiocytes and multinucleated giant cells, resulting in a granulomatous reaction.
Complete surgical excision is the treatment of choice.
Case contributed by Dr. Mithilesh Chandra
Rheumatoid nodule
Rheumatoid nodules occur in about 20% of patients with rheumatoid arthritis, especially in seropositive disease, as asymptomatic, skin-colored, subcutaneous nodules over extensor surfaces such as elbows and knees. Accelerated rheumatoid nodulosis refers to the development of new painful rheumatoid nodules on the hands, feet and ears in patients with chronic rheumatoid arthritis under treatment with methotrexate, azathioprine and anti-TNF agents.
On biopsy, it is a classical example of a red palisading necrobiotic granuloma. The dermis and subcutis demonstrate irregular areas of necrobiosis surrounded by a palisade of histiocytes with occasional lymphocytes, neutrophils and multinucleated giant cells. The central necrobiotic foci appear intensely eosinophilic and amorphous due to fibrin. Uncommonly, acute vasculitis is seen in the surrounding vessels. Long standing lesions may show dense fibrosis and cystic degeneration of necrobiotic foci.
Subcutaneous granuloma annulare is a close differential diagnosis, which is characterized by mucin deposition and therefore appears as a blue palisading granuloma.
Case contributed by Dr. Mithilesh Chandra
Eosinophilic annular erythema
Eosinophilic annular erythema (EAE) is a rare benign recurrent disease, originally described in children, characterized by persistent non-pruritic, urticarial annular lesions with marked tissue eosinophilia. The lesions present as solitary or multiple erythematous papules or nodules that migrate and evolve to form figurate, annular plaques with a clear centre and an elevated erythematous border, mainly on the trunk and extremities. Clinically, the differential diagnoses include erythema annulare centrifugum, erythema chronicum migrans, disseminated granuloma annulare, subacute cutaneous lupus erythematosus and urticarial vasculitis. It is now believed that EAE is a peculiar clinical variant in the spectrum of Wells' syndrome.
On biopsy, there is dense superficial and deep perivascular and interstitial lympho-histiocytic infiltrate with abundant eosinophils in the dermis. Basal vacuolar degeneration and dermal mucin deposition have been described in a few cases. Well-developed and long standing lesions may demonstrate flame figures. Histologically, differential diagnoses include insect bite and drug reactions.
Case contributed by Dr. Mithilesh Chandra
Herpes genitalis
Herpes genitalis presents as small grouped vesicles, often on an erythematous base, most frequent on the glans, prepuce and shaft of the penis in males and external genitalia, mucosae of the vulva, vagina and cervix in females. Pain and dysuria are common. Although HSV-2 previously accounted for approximately 90% of the cases, there has been recent increase in the proportion of cases attributable to HSV-1.
On biopsy, the early change is increasing edema of the keratinocytes, which progresses to ballooning degeneration. Some adjacent keratinocytes fuse and appear large and multinucleate. A number of cells show acantholysis, while others rupture as a result of extreme ballooning degeneration (reticular degeneration), resulting in an irregular intraepidermal vesicle containing groups of keratinocytes, many of which are multinucleate. The nuclei of keratinocytes show margination of chromatin and may contain basophilic and/or pale ground-glass inclusions (Cowdry type A inclusions). The underlying dermis is usually intensely infiltrated by mixed inflammatory cells.