Histopathologic Terminology

The use of descriptive terms in histopathology is a valuable method for standard communication which allows both the pathologist and the clinician to understand specific histologic characteristics of biological materials. One or more of these characteristics may be specific for certain lesions, thus allowing a more precise diagnosis. In some cases, knowledge of such characteristics can also help the clinician make a provisional diagnosis that might allow therapeutic decisions such as to biopsy or not, or to treat medically or to observe.

In the following pages we describe and illustrate the more common descriptive terms in histopathologic diagnosis, which are used throughout this book.

Acantholysis

Acantholytic Basal Cell Carcinoma

Acantholysis is the loss of cohesion between epidermal (or epithelial) cells leading to the formation of intraepidermal clefts, vesicles, or bul-lae. Primary acantholysis results from dissolution or separation of the desmosomes between unaltered cells. Secondary acantholysis occurs between damaged cells such as during viral infection. An example of primary acantholysis in pemphigus vulgaris is shown.

Acanthosis

Hyper Acanthosis

Acanthosis is an increase in the thickness of the squamous cell layer (stratum spinosum) of the epidermis. Acanthosis often results in elongated projections of the epidermis into the dermis, as shown in this example.

Actinic Elastosis

Actinic Elastosis Histology

Actinic elastosis, also referred to as solar elastosis, is characterized by lightly basophilic, irregular, thickened elastic fibers in the dermis. Individual fibers are sometimes not evident, and there may be only an amorphous mass of lightly basophilic material in the dermis. Elastic tissue stains may be used to highlight actinic elastosis.

Apoptosis

Apoptotic Cell Chromatin Condensation

Apoptosis is programmed cell death recognizable morphologically by chromatin condensation, cell shrinkage, and hypereosinophilia. Apoptotic cells with no remaining nucleus appear as homogenous, eosinophilic, round structures termed colloid bodies or cytoid bodies. Apoptosis requires energy, transcription of new genes, and protein synthesis.

Ballooning Degeneration of the Epidermis

Cytoid Bodies Skin

In ballooning degeneration of the epidermis, marked intracellular edema leads to acantholysis and subsequent formation of an intraepidermal vesicle or bulla. Ballooning degeneration is characteristic of cutaneous viral infections.

Birefringence

Birefringence is the splitting of a light wave into two waves that have perpendicular polarizations and speed of travel. Birefringence results from a substance having different indexes of refraction, and is thus also referred to as double refraction. Birefringent objects appear as shining bodies on a dark background when viewed with polarized light. Birefringent objects are usually white or yellow in sections stained with hematoxylin and eosin. Collagen and hair are normal structures in the skin that are birefringent, while foreign bodies are the most frequent extraneous birefringent materials. Amyloid is birefringent when stained with Congo red, as shown here.

Pulmonary Amyloidosis Congo Red

Bulla

Clear Fluid Filled Cyst Eyelid Rim

A bulla is a fluid-filled blister greater than 0.5 or 1 cm in diameter, depending on the author. Bullae may be subcorneal (shown), intraepidermal, suprabasilar, or subepidermal.

Colloid Body

Colloid Bodies

Colloid bodies are also known as cytoid bodies, Civatte bodies, hyalin bodies, and apoptotic bodies. They are apoptotic epidermal cells (keratinocytes) lacking nuclei and appear as homogeneous, eosinophilic, and round structures. Colloid bodies are not specific for any disease, but they are commonly seen in lupus erythematosus, lichen planus, and graft-versus-host disease.

Decapitation Secretion

Pyknotic Dyskeratotic Cells

Decapitation secretion is characteristic of apocrine cells. During decapitation secretion, portions of the apical eosinophilic cytoplasm of the cells is pinched off into the lumina lined by the apocrine cells.

Dyskeratosis

The meaning of the term dyskeratosis varies depending on the disease. In acute graft-versus-host disease, lichen planus, and lupus erythematosus, dyskeratot-ic cells are cells undergoing apoptosis and are smaller than adjacent epidermal keratinocytes, have brightly eosinophilic cytoplasm, and shrunken hyper-basophilic nuclei (see Apoptosis). In acan-tholytic dermatosis, the dyskeratotic cells are also termed "corps ronds" and have a central, basophilic, pyknotic nucleus surrounded by a clear halo and enveloped within a basophilic or eosinophilic rim. Neoplastic dyskeratosis is manifest as brightly eosinophilic bodies, sometimes with remnants of nuclei, within a tumor (shown). These bodies represent neoplastic cells undergoing apoptosis.

Civatte Bodies

Epidermotropism

Blast Cells Atypical Lymphocytes

Epidermotropism is the presence of atypical lymphocytes in the epidermis without spongiosis and is characteristic of mycosis fungoides. The atypical lymphocytes in the epidermis may occur singly surrounded by a clear halo or they may form small clusters referred to as Pautrier microabscesses.

Epithelioid Cells

Clear Cell Dyskeratosis

Epithelioid cells are activated macrophages that have an epithelial-like appearance. They are large cells with oval to elongated nuclei, eosinophilic cytoplasm, and indistinct cell borders. They occur singly or may form groups termed granulomas.

Exocytosis

Exocytosis Example

Exocytosis refers to the presence of inflammatory cells within the epidermis in conjunction with spongiosis. Exocytosis is characteristic of inflammatory dermatoses.

Fibrinoid Degeneration (Necrosis)

Ballooning Degeneration Epidermis

Fibrinoid degeneration, also referred to as fibrinoid necrosis, is manifest by the deposition of fibrin within vessel walls or dermal collagen. Fibrin is homogeneous and eosinophilic in sections stained with hematoxylin and eosin. In the skin, fibrinoid necrosis of vessel walls is seen in leukocytoclastic vasculitis, while fibrin deposition in dermal collagen is seen in rheumatoid nodules and sometimes in lupus erythematosus, especially the systemic variant. An orbital vessel in a patient with Wegener's granulomatosis is shown.

Foam Cell

Foam Cell Breast

A foam cell is a macrophage laden with lipid, causing it to have vacuolated, bubbly-appearing cytoplasm.

Foreign Body Giant Cell

Multinucleated Giant Cells Tubule

A foreign body giant cell is a multinucleated giant cell derived from fusion of epithelioid cells (activated macrophages). Foreign body giant cells are characterized by their large size and haphazardly arrayed nuclei.

Granulation Tissue

Granulation Tissue

Granulation tissue is the hallmark of wound healing, and the term comes from the soft, pink, granular appearance when viewed from the surface of a wound. Histologically, granulation tissue consists of a proliferation of small blood vessels and fibroblasts, often accompanied by edema.

Granuloma

Zirconium Granuloma

A granuloma is a microscopic aggregate containing varying proportions of activated macrophages (epithelioid cells), multinucleated giant cells resulting from fusion of epithelioid cells, and other mononuclear leukocytes (lymphocytes, plasma cells, monocytes, and macrophages). Foreign body granulomas are reactions to relatively inert particles and typically have multinucleated giant cells, macrophages, and usually only small numbers of epithelioid cells. Immune or allergic granulomas are a response to insoluble particles that can induce a cell-mediated immune response; they may result from foreign substances such as zirconium, beryllium, or dyes used for tattoos, or microbes such as Mycobacterium tuberculosis and fungi. Immune/allergic granulomas typically contain abundant epithelioid cells and variable numbers of multinucleated giant cells. Other descriptors used for granulomas are sarcoidal, tuberculoid, and palisading. Sarcoidal granulomas, also termed naked granulomas, have epithelioid cells and multinucleated giant cells with only a sparse periphery of lymphocytes (shown). Sarcoidal granulomas are characteristic not only of sarcoidosis, but they also are seen in some infections, granulomatous rosacea, orofacial granulomatosis (including the Melkersson-Rosenthal syndrome), and as a response to some foreign materials. Tuberculoid granulomas have epithelioid cells, multinucleated giant cells (especially Langhans' giant cells), and a moderate to dense periphery of lymphocytes. Central necrosis ("caseation necrosis") may or may not be present. Tuberculoid granulomas are characteristic not only of Mycobacterium tuberculosis infection but are also seen in other infectious diseases. Palisading granulomas in the skin have a central zone of degenerated collagen (termed "necrobiosis") surrounded by macrophages, palisading epithelioid cells, lymphocytes, and variable numbers of multinucleated giant cells. Palisading granulomas are characteristic of granuloma annulare, necrobiosis lipoidica, rheumatoid nodules, and necrobiotic xanthogranuloma.

Horn Cyst

Palisading Granulomas And Microabscesses

A horn cyst is a circumscribed, round, intraepidermal accumulation of keratin. Keratin-filled invaginations of the epidermis are referred to as "pseudo-horn cysts." Both horn cysts and pseudo-horn cysts are characteristic of seborrheic keratoses, though they may also be seen in other neoplasms of the skin.

Hydropic Degeneration of Basal Layer

Hydropic Degeneration Skin

Hydropic degeneration of the basal layer, also termed vacuolar degeneration and liquefactive degeneration, refers to degeneration of the basal cell layer characterized by formation of clear spaces (vacuoles) beneath the basal layer. It is a histologi-cal feature prominent in lupus erythematosus, erythema multiforme, graft-versus-host disease, as well as other dermatological diseases not common to the eyelids.

Hyperkeratosis

Epidermis Hyperkeratosis

Hyperkeratosis is increased thickness of the stratum corneum (horny layer) of the epidermis. Hyperkeratosis may result from orthokeratosis, parakeratosis, or a combination of these two. Refer to Orthokeratosis and Parakeratosis (below).

Keratohyalin

Remnant Nucleus Parakeratosis

Keratohyalin is seen as darkly basophilic granules found in keratinocytes of the granular layer (stratum granulosum) of the epidermis. Keratohyaline granules form matrix that cements cytokeratin tonofibrils together resulting in increased strength and stability.

Koilocyte

Koilocytes Skin

Koilocytes are vacuolated keratinocytes with eccentrically placed, basophilic, shrunken nuclei surrounded by clear halos. They are found in the upper spinous and granular cell layers of the epidermis in human papillomavirus infections (verruca vulgaris, in the eyelid).

Langhans' Giant Cell

Giant Cell Reaction Dermis

Langhans' giant cells are multinucleated giant cells derived from fusion of epithelioid cells (activated macrophages). They are large cells with their nuclei arranged along the periphery of the cell forming an arc. Langhans' giant cells are non-specific, and they may be seen in both immune-type granulomas (such as sarcoidosis and tuberculosis) and foreign body granulomas.

Lichenoid Inflammation

Tattoo Lichenoid Reaction

Lichenoid inflammation or lichenoid reaction pattern refers to a dense band of lymphocytes clustered around the interface between the epidermis and dermis, often causing it to be obscured. Lichenoid inflammation is common to many dermatological conditions, though only a few, such as erythema multiforme and graft-versus-host disease, are seen in the eyelids.

Melanophage

Macrophage With Phagocytized Fungi

A macrophage containing phagocytized melanin is referred to as a melanophage. Melanin granules are dark brown and non-refractile in sections stained with hematoxylin and eosin. Melanophages are seen in the dermis in inflammatory conditions affecting the epidermis, as well as in neoplasms such as seborrheic keratosis, blue nevus, and melanomas.

Necrobiosis

Cellular Blue Nevus

Necrobiosis refers to death of cells or tissue due to aging or overuse. Zones of smudged or homogenized dermal collagen characterize it histologically. Necrobiosis is often seen as the center of a palisading granuloma. In granuloma annulare, the necro-biotic zone contains mucin, while in rheumatoid nodules there is usually fibrin within the necrobiotic area. The photomicrograph shows a zone of necro-biosis at the top left, surrounded by palisading epithelioid cells in a case of granuloma annulare involving the eyelid.

Orthokeratosis

Orthokeratosis

Orthokeratosis is an increased thickness of the horny layer (stratum corneum) by anucleate (i.e., normal appearing) cells. Orthokeratosis my be compact, laminated, or have a basket-weave configuration.

Papillomatosis

Hyperkeratotic Seborrheic Keratosis

Papillomatosis is characterized histologically by abnormally elongated epidermis and papillary dermis resulting in irregular undulation of the epidermal surface. Papillomatosis is seen most commonly in seborrheic keratosis and verruca vulgaris (shown).

Parakeratosis

Parakeratosis Meaning

Parakeratosis is an increased thickness of the horny layer (stratum corneum) by nucleated cells. Parakeratosis represents a defect in cellular differentiation and is usually associated with a thinned or absent granular layer. An example of parakeratosis in a specimen with actinic keratosis is shown here.

Pigment Incontinence

Melanin Incontinence

Pigment incontinence refers to the release of melanin granules from the epidermis and its resulting deposition in the upper dermis either free or within macrophages (melanophages).

Pseudocarcinomatous (Pseudoepitheliomatous) Hyperplasia

Pseudocarcinomatous Hyperplasia

Pseudocarcinomatous hyperplasia is a histopatho-logical reaction pattern manifest as irregular hyper-plasia of the epidermis with prominent acanthotic downgrowth of the epidermis. The epidermal proliferation occurs in response to a wide range of stimuli including chronic irritation, trauma, and dermal fungal infections. Pseudocarcinomatous hyperplasia differs from squamous cell carcinoma by having minimal cytological atypia and fewer mitoses.

Psoriasiform Dermatitis

Psoriasiform Dermatitis

Psoriasiform dermatitis, also known as superficial dermatitis with psoriasiform proliferation, refers to a form of epidermal thickening with uniform elongation of rete ridges that extend downward into the dermis. Parakeratosis is common. The nature of the inflammatory cells in the dermis, the presence and degree of spongiosis, and the presence of exocytosis are features that aid in rendering a more specific diagnosis.

Shadow Cell

Squamous Cell Carcinoma Ghost Cell

Shadow cells, also known as ghost cells, are characteristic of pilomatrixomas. They are pale, eosinophilic cells with a clear area in place of the nucleus.

Spongiosis

Moderate Spongiosis

Spongiosis is intercellular edema between squamous cells of the epidermis. It is characteristic of acute dermatitis and may lead to micro- and macro-vesicles (spongiotic blisters). Intracellular edema may accompany severe spongiosis, resulting in bursting of epidermal cells and formation of multilocular bulla.

Squamous Eddies

Squamous Eddies Picture

Squamous eddies are whorled onionskin-like foci of brightly eosinophilic keratinocytes. They are a typical feature of irritated seborrheic keratoses.

Touton Giant Cell

Touton Giant Cell Histology

Touton giant cells are multinucleated giant cells derived from fusion of epithelioid cells (activated macrophages). They have a ring of nuclei surrounding eosinophilic non-vacuolated cytoplasm centrally and lipid-filled foamy cytoplasm peripherally. They are characteristic of xanthogranulomas.

Vesicle

Psoriasiforme Hyperplasie
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