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Even when the clinical appearance of the lesions strongly suggests MF, a biopsy may not bring histologic proof in favor of this diagnosis. The papillomatosis irregular acanthosis may include, among others, the paucity and low frequency of anecdotic histopathologic criteria associated with MF, namely epidermotropism, Pautrier microabscesses and lymphocytes with cerebriform nuclei, the possibility that the biopsy site might be unrepresentative for the whole rash, or even the fact that MF infiltrates can masquerade as different reactive conditions that share similar patterns of inflamation, such as psoriasiform, lichenoid or eczematous diseases.
Vice versa, even when classical clues of MF papillomatosis irregular acanthosis present in a given specimen, their interpretation has to be carefully made, since various reactive inflammatory conditions have been reported to share similar histopathologic features with early MF, such as drug-induced T-cell pseudolymphoma 89lichen sclerosus et atrophicus 10persistent pigmented purpuric dermatoses 11actinic reticuloid 12eczematous dermatitides 1314lymphomatoid contact dermatitis 15 papillomatosis irregular acanthosis, benign lichenoid keratosis 16connective tissue disease 17and skin infections and infestations 1819among others.
In our study, we tried to comparatively assess the frequency of occurrence of different histopathologic criteria papillomatosis irregular acanthosis biopsies from early lesions of MF, respectively from various entities that microscopically mimick MF.
In the category of epidermal reaction Figure 1 we investigated the appearance of spongiosis, psoriasiform hyperplasia, interface dermatitis, epidermal atrophy and the presence of elongated mounds of parakeratosis. A significant difference between Papillomatosis irregular acanthosis and mimickers group was recorded for the presence of psoriasiform hyperplasia In our opinion, this finding signifies a relative lack of epidermal reactivity as a response to the presence of lymphomatous infiltrate.
When occured in MF cases, psoriasiform hyperplasia was rather irregular, lichen simplex chronicus-like, and was associated in a large proportion with a dense, band-like dermal infiltrate, finding which represents a combined psoriasiform and lichenoid pattern, as previousely described for MF Parakeratosis, manifested as a thin, long band on top of the affected epidermis, was observed more frequently with MF biopsies Focal spots of parakeratosis manifested as isolated columns and mounds of parakeratosis were more oftenly seen in the control group, but this feature was not recorded when parakeratosis band was not continuous over at least one quarter of biopsy section.
In other words, spongiosis was a rather common event in early MF. This finding suggests that, when detected in biopsies for clinical papillomatosis irregular acanthosis of early MF, papillomatosis irregular acanthosis low degree of spongiosis should not be the sole criterion for MF exclusion.
Figure 1. To be able to quantify the degree of epidermotropism, we looked for various patterns described before papillomatosis irregular acanthosis patch and plaque-type MF 2122like the presence papillomatosis papillomatosis irregular acanthosis acanthosis lymphocytes aligned along the basal layer of the epidermis basilar lymphocytesa diffuse spread of lymphocytes into the epidermis pagetoid lymphocytesthe presence of lymphocytes in clusters larger than 3 cells Pautrier microabscesses and areas of spongiosis where exocytosis of lymphocytes overwhelms the degree of intercellular edema usually seen with spongiotic papillomatosis irregular acanthosis dysproportionate exocytosis Figure 2.
A noteworhty feature was the occurrence of oxiuros y ajo exocytosis in MF cases as compared to mimickers This finding correlates with the frequency of papillomatosis irregular acanthosis detected in Urothelial papilloma with atypia cases.
In the same time it confirms that spongiosis may not be a truly exceptional event in early MF, but when joined by a dysproportionate number of lymphocytes in the epidermis, it may even be a feature of MF. Another notable observation regards the presence of Pautrier microasbscesses, defined as collections of intraepidermal lymphocytes devoid of spongiosis.
Their presence correlates well with MF, since this feature was recorded in none of the control cases. They represent clusters of Langerhans cells papillomatosis irregular acanthosis have been described before as pseudo-Pautrier abscesses, and usually appear in association with inflammatory dermatoses Their occurrence should not be regarded as a histopathologic clue for MF.
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Besides their cytologic features, the pseudo-Pautrier collections commonly develop in a background of spongiosis, a feature that may help in their discrimination from real Pautrier microabscesses, which are devoid of spongiosis. Although traditionally linked to cutaneous lym- Figure 2. Atypical MF lymphocytes have been clasically described as having a convoluted, cerebriform nucleus, sometimes large, hyperchromatic, with a perinuclear halo.
We tried to independently asses all papillomatosis irregular acanthosis features in our study, and observed that less than one quarter of MF cases showed at least one form of lymphoid atypia Figure 3.
The single most frequent atypical feature in the control group was the perinuclear halo, which can be possibly interpreted as a processing artefact.
Together with hyperchromasia, it had no discriminatory value between MF and mimicker groups. Cerebriform cells, despite being classicaly related to MF, were spotted in just two cases of our study, suggesting that their appearance is an exceptionally rare event in practice.
One reason for that may be of technical nature, since cell morphology can be influenced by section thickness, tissue processing protocol, staining etc. The occurrence of hypertrophic lymphocytes was the most reliable feature of atypia, reaching statistical significance Lymphocyte atypia in MF: a Papillomatosis irregular acanthosis and hyperchromatic tumoral lymphocytes at the dermalepidermal junction; b Cerebriform lymphocytes in dermal infiltrate.
We defined dermal reaction as changes induced by the presence of lymphoid infiltrate and included in this category some features such as papillary dermal fibrosis, papillary dermal edema, purpura and pigmented macrophages melanophages and siderophages Figure 4.
It might be determined by the interaction of tumoral cells and their cytokine secretion with matrix proteins and matrix remodelation Edema of the papillary dermis was deemed unusual in MF by other investigators, although it was recorded in some of our MF cases.
For example, in the largest series of MF cases to date, Massone et al.
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The presence of papillary dermal edema in All other dermal reaction changes did not reach statistical significance between the groups. An interesting finding is the occurence of extravazated erythrocytes and siderophages in some early MF cases, usually those cases with poikilodermatous changes.
Purpura was seen with similar papillomatosis irregular acanthosis in both our groups. When attempting a histopathologic diagnosis, the presence of siderophages naturally brings into question the possibility of a pigmented papillomatosis irregular acanthosis dermatosis PPD.
In some patients, MF and PPD have been shown to coexist 29a finding challenged by other investigators 11 MF in appropriate clinical setting.
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But similar patterns of inflamation can be manifested in cutaneous biopsies of secondary syphilis, actinic reticuloid, lichen simplex chronicus among others, thus the architectural criteria alone are insufficient for the diagnosis of MF On the other hand, a strictly perivascular infiltrate is rather common in reactive dermatoses and make MF unlikely, unless epidermotropic features or atypical lymphocytes are obvious. When looking at the composition of dermal infiltrate, there were 6 biopsies in MF group Similarly, eosinophils were recorded in There was no statistical difference between gropus, meaning that the presence of low numbers of eosinophils in the dermal infiltrate could not be used as a histopathologic criterion to certainly rule out early MF.
None of the mimicker cases showed higher number of eosinophils. A reason for the relative paucity of eosinophils in the mimickers group might be the fact that cases with overtly more eosinophils in the infiltrate were not selected, because they did not fulfill the criteria of histopathological mimickers of MF.
Contrary to our finding, Dalton et al. An argument for the presence of eosinophils in some of our early MF lesions might be unknown previous treatment of lesions with topical agents, Figure 4. Regarding the distribution of the dermal infiltrate Figure 5the lichenoid pattern defined as a dense, band-like infiltrate in the upper dermis correlated well with MF lesions The presence of a dense lichenoid infiltrate usually explains the palpable nature of the plaquetype MF lesions, and when seen in biopsies along with other architecutral changes, like psoriasiform epidermal hyperplasia, can be highly indicative of Figure 5.
papillomatosis irregular acanthosis
All subtypes of epidermotropism gained high specificity for early MF, but their sensitivity was usually low to papillomatosis irregular acanthosis used as pivotal diagnostic criteria. Although, in theory, lymphocyte atypia is traditionally considered a valid histopathologic clue for cutaneous lymphoma, the occurrence of cytologic features may vary depending on tissue processing and staining protocols.
Additionally, papillomatosis irregular acanthosis study showed that morphologic criteria routinely assigned to reactive conditions, such as spongiosis, eosinophils and purpura with siderophages, were present in similar degrees in both case groups and may not allow differentiation of MF from mimickers. Despite recent advancements in the field of cutaneous lymphoma, evaluating biopsies from suspected cases of MF in its early stages and rendering a definitive diagnosis remain challenging tasks.
Provided the biopsy is accompanied by comprehensive clinical history, good description of the lesions, clinical pictures and efficient communication with reffering physician, we believe that a diagnosis of MF can be made with confidence.
In certain cases, however, relying just on histopathologic criteria might prove erroneous, since there is no single criterion sensitive and specific enough to discriminate between early MF papillomatosis irregular acanthosis a pletora of reactive inflammatory rashes.
This work is licensed under a Creative Commons Attribution 4. Cutaneous lymphoma incidence patterns in the United States: a population-based study of cases. Stage I mycosis fungoides: frequent association with a favourable prognosis but disease progression and disease-specific mortality may occur.
Br J Dermatol.