Extranodal NK/T-cell lymphoma, nasal type.

Natural killer (NK) cell lymphomas and leukemias are a rare but clinically important group of neoplasms. Most of these tumors are aggressive, with a high rate of mortality. They include extranodal NK/T-cell lymphomas of nasal type and aggressive NK-cell leukemias. Both are Epstein-Barr virus (EBV) associated and show similar epidemiologic features. A closely related entity seen mainly in children is hydroa vacciniforme-like lymphoma, which also is EBV positive. EBV influences the pathophysiology of these tumors, through the induction of cytokines and chemokines. The differential diagnosis of NK-cell malignancies includes fulminant EBV-associated T-cell lymphoproliferative disorder, a condition referred to in the past as fatal infectious mononucleosis. Benign proliferations of NK cells can be seen in association with viral infection. The disease formerly referred to as blastic NK-cell lymphoma is now considered to be a malignancy derived from a dendritic cell precursor.

The pathology of NK-cell lymphomas and leukemias.

:Cutaneous eruptions caused by herpes simplex 1/2 (HSV-1/2) and herpes varicella/zoster (VZV) represent common dermatoses. In some cases, they present with atypical clinical and/or histopathologic features, including presence of dense lymphoid infiltrates with atypical lymphocytes simulating

Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster) : A broad spectrum of presentations with common pseudolymphomatous aspects

Abnormal substances in the nuclei that can be observed by light microscopy are often broadly referred to as nuclear inclusions. Although their recognition in the appropriate clinicopathological settings can aid in the diagnosis of some disease entities and tumor types, they can also be a source of error. There are 2 morphologically distinct types of inclusions with different mechanisms of formation and diagnostic significance, including bona fide nuclear inclusions and nuclear pseudoinclusions. Bona fide nuclear inclusions result from accumulation in the nuclei of viral particles, cytoplasmic materials (such as surfactant, immunoglobulin, and glycogen), biotin, nuclear lamins, or polyglutamine. Some of them are diagnostically helpful, such as surfactant inclusion, which can support the pulmonary origin of an adenocarcinoma, whereas others may be misleading, such as biotin inclusion, which can be mistaken for herpes infection. Nuclear pseudoinclusions, which represent invaginations of cytoplasm into the nucleus, are delimited by the nuclear membrane. Although not totally specific, they are particularly common in papillary thyroid carcinoma, meningioma, and usual ductal hyperplasia of the breast and hence may aid in the diagnosis of these entities. Nuclear pseudo-pseudoinclusions, which are artefactual bubbles in the nuclei that mimic nuclear pseudoinclusions or clear nuclei, can lead to misdiagnosis of follicular adenoma or hyperplastic nodule as papillary thyroid carcinoma.

Nuclear Inclusions and Pseudoinclusions: Friends or Foes of the Surgical Pathologist?:

Herpes simplex virus and varicella zoster virus are double-stranded DNA viruses that commonly infect humans, resulting in cutaneous manifestations. Diagnosis is generally made based on clinical findings; however, when the presentation is atypical, biopsy can aid in making a correct diagnosis. The classic histopathological findings of herpetic infection are well established (acantholysis, ballooning degeneration, intranuclear inclusions, multinucleation, necrosis, and formation of vesicles or ulcers). Herpes infection can also cause histopathological changes in many dermal structures. Furthermore, herpes can masquerade as a variety of hematologic malignancies or benign cutaneous conditions. The histopathological spectrum of herpes infections is reviewed and discussed.

Jeffery I Feldman

Papers

Florid CD4+, CD56+ T-cell infiltrate associated with Herpes simplex infection simulating nasal NK-/T-cell lymphoma.