We report histopathological evidence of mycoplasma infestation of the squamous epithelium presenting non-inflammatory benign acanthotic papule of the skin in an adult male, not reported in the previous literature. Sections showed hyper-chromatic basal layer with marked acanthosis and inclusions with nucleic body surrounded by cytoplasm devoid of cell wall. Histopathological evidence was diagnostic of mycoplasma infested non-inflammatory benign acanthotic papule of the skin. Nuclear and cytoplasmic microbial inclusions in the epithelial cells, and keratinocytic and cytolytic changes could be the source of signals to the basal strata for benign epitheliomatous proliferation, giving rise to non-inflammatory benign acanthotic papule.
Keywords: Acanthosis, benign, infestation, mycoplasma, papule, skin
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Naim M, Amin SS, Zaman S, Naim A. Non-inflammatory infestive benign acanthotic papule of the skin: Histopathological evidence. Ann Trop Med Public Health 2012;5:517-9
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Naim M, Amin SS, Zaman S, Naim A. Non-inflammatory infestive benign acanthotic papule of the skin: Histopathological evidence. Ann Trop Med Public Health [serial online] 2012 [cited 2020 Nov 29];5:517-9. Available from: https://www.atmph.org/text.asp?2012/5/5/517/105149
Diseases of the infestive nature are serious world health problems particularly in the developing and tropical regions.  Researches in the recent years have shown that new pathogens were emerging with new pathogenic trends.  A serious trend emerging in some pathogens was microbial capability to evade detection by the host inflammatory-cell immune apparatus in immune-competent patient, causing infestation of the tissue without inflammatory cell response, and responded by the host epithelial cells by phagocytising microbe and undergoing epitheliomatous proliferation.  Here we report histopathological evidence of mycoplasma infestation of the squamous epithelium presenting non-inflammatory benign acanthotic papule of the skin in an adult male, not reported in the previous literature.
A 38-year-old Indian male with a hyper pigmented papule on the left cheek for the last four months not responding to systemic and local antibiotic with corticosteroid therapy was referred to the skin specialist in this hospital. A papule of about 3 mm size showing surface hyperkeratosis and dry appearance was excised by the consultant and submitted for histopathological diagnosis. Findings on routine urine, blood, and serological tests for HIV and venereal disease were unremarkable.
Sections [Figure 1] stained with haematoxylin and eosin (H and E), and periodic acid Schiff (PAS) stains, showed hyper-chromatic basal layer with marked acanthosis resulting in hyper plastic, large, hyper-chromatic, benign acanthocytes in the par basal and prickle-cell layers, and dilated intercellular spaces showing faintly stained inclusions presenting appearance of rosary of beads in the inter cellular spaces (arrows). Inflammatory cells were remarkably absent.
|Figure 1: Showing hyper chromatic acanthotic basal strata, and poorly stained rosary-bead inclusions (arrows) in the intercellular spaces (a) H and E, x1000), and (b) (PAS x 1000)|
Silver stain [Figure 2] showed inter-cellular, intra-cytoplasm, and intra-nuclear (arrow) argyrophillic inclusions of up to five micron diameter in the basal par basal strata, prickle-cell layer, and superficial layers. Inflammatory cells were not seen in any of the parasitized layers. Surface layers showed nuclear distortions (black arrows), and absence of the granular layer, with early hyper keratosis (black arrow heads).
|Figure 2: Showing the basal strata [a], prickle-cell layer [b], and superficial layers [c and d] depicting intracellular, cytoplasmic, and nuclear (white arrow) inclusions, distorted nuclei (black arrows), and hyper keratosis (black arrow heads) (Silver Stain x500)
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Under higher magnification [Figure 3] budding forms and chains of beads shaped inclusions, comprising of dark argyrophilic nucleic body surrounded by light stained cytoplasm devoid of cell walls either capsules (black arrow heads) were characteristic of Mycoplasma.  Inclusion infested epithelial-cell-nuclei (white arrow) were distorted in contour and chromatin content, and did not show mitosis or binary fission as visible in cases of infestation by other carcinogenic species of mycoplasma.  Occasional cells showed cytolytic changes (cc) without any inflammatory cell response.
|Figure 3: Showing the inclusions, comprising nucleic body surrounded by cytoplasm devoid of cell wall (black arrow heads). Inclusion infested distorted nuclei (white arrow) did not show mitosis or binary fission. Occasional cell showed cytolytic change (cc) (Silver stain x 1250)
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After excision patient was on six week course of erythromycin. No recurrence or new lesion is reported in last three months of follow up.
Histopathological evidence in this case was diagnostic of Mycoplasma infested non-inflammatory benign acanthotic papule of the skin. Macular and papular skin lesions are known to occur in the Mycoplasma pneumonia infection diagnosed as Steven-Johnson syndrome. Such lesions, however, are multiple, appear in rash crop, last for a fortnight, and mycoplasma inclusions are not seen in the skin lesions.  Presently patient had no respiratory symptoms, and presented single non-healing skin papule of four months duration showing well defined mycoplasma inclusions in the nuclear, cytoplasmic, and inter cellular compartments in the epidermis, which differentiated the present lesion from the Steven-Johnson syndrome,  and erythema multiforme (von Hebra).  Morphology of the mycoplasma inclusions, their poor PAS staining character, nuclear and cytoplasmic changes in host epithelial cells, and absence of inflammatory cell response, in the present case, also differentiated presently Argyrophilic glycol-heterogeneous  (AGH) Mycoplasma spp inclusions from the earlier known carcinogenesis inducing strains of Mycoplasma.  Nuclear and cytoplasmo-lytic set of pathological changes, and well preserved infested cells and compartment wise inclusions, also ruled out possibilities of contamination of the biopsy-in-formalin, diagnostic of in vivo mycoplasma infestation. Such (AGH) Mycoplasma spp infested non-inflammatory benign acanthotic papule of the skin, as presently observed, was not reported in the earlier literature.
Mycoplasma infested acanthocytes, in the present case, did not show microscopic evidence of mitosis either fission, to explain acanthosis or formation of the papule. The hyper-plastic activity observed in the basal cell strata appeared to be responsible for the benign acanthosis or thickened acanthocytes-cell-layer, in this case. Parasitisation or phagocytises of microbe by the epithelial cells, in absence of any inflammatory cells, could be the possible source of (supra-kine) signals to the basal strata for benign epitheliomatous proliferation,  giving rise to benign, epitheliomatous nodule, or papule.
Mycoplasma is a hazardous microbe of micron sizes, wide spread in the nature globe wise, particularly in the tropical regions, and known to cause disease in the plants, animals and man.  In the recent decades mycoplasma spp. are reported to have been isolated from large number of different tissues particularly transplants which, on account of non visualization of the organism in formalised paraffin H and E sections under usual magnifications, caused controversy over the years of unexplainable mycoplasma-contamination of the assay samples.  Histopathological findings, of the nuclear, cytoplasmic, and inter-cellular inclusions, as in the present case, may be confirmatory evidence of in vivo Mycoplasma infestation of the tissue, and may serve as better dependable investigation for the diagnosis of Mycoplasma infestive diseases in man, than the micro-assay. 
Mycoplasma is defined as a bacterial microbe without cell wall,  although it is known to share some features of the fungi, like filamentous forms,  superbly surface-antigenic apparatus (in some cases) capable of evading inflammatory cell immune apparatus of the host  causing infestation without inflammatory cells response, and signalling basal cell proliferative activity and early keratinocytic changes.  Further interestingly some of Mycoplasma spp are known to be glycol-heterogeneous,  and cause suppression of the host mononuclear cells. 
- Human skin is susceptible to infestation by a glycol-heterogeneous Mycoplasma (GHM) spp.
- Such Mycoplasma (GHM) spp infested squamous epithelium presents with argyrophilic intra-cellular, intra-cytoplasmic and intra-nuclear inclusions of the characteristic of oval shapes of mycoplasma. Such Mycoplasma (GHM) inclusions infested cells show cytolysis without inflammatory cell response, and early keratinocytic change.
- Parasitisation or phagocytises of the microbe by the epithelial cells, keratinocytic and cytolytic changes could be the source of signals to the basal strata for benign epitheliomatous proliferation, giving rise to non-inflammatory benign acanthotic papule.
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Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]