Search

The occurrence of pseudolymphomatous infiltrates in cutaneous lupus erythematosus (cLE) is described mainly in lupus panniculitis and lupus tumidus/lymphocytic infiltration of the skin (Jessner-Kanof). We collected 15 cases of pseudolymphomatous cLE other than lupus panniculitis and lupus tumidus (M:F = 4:11; age range: 23-79 years; mean age: 50.9 years; median age: 57 years). Of the 15 cases, 9 (60%) were characterized by dense nodular infiltrates. Three cases (20%) showed an angiocentric pattern with cytological atypia of lymphoid cells; 2 cases (13.3%) showed a band-like infiltrate mimicking mycosis fungoides, and 1 case had mixed features of the band-like and angiocentric patterns. Clues to the histopathological diagnosis of cLE were presence of interface dermatitis, clusters of plasmacytoid dendritic cells, and dermal mucin deposition. Our study shows that the spectrum of pseudolymphomatous presentations of cLE is broader than previously described, including band-like cases that may be misconstrued as mycosis fungoides, and angiocentric cases that may be misinterpreted as an aggressive lymphoma. Recognition of such cases is possible only on careful clinicopathologic correlation and requires a high level of histopathological suspicion to allow a correct diagnosis and the proper management of the patients.

The pathogenesis of leprosy is still not fully understood. Several studies have been performed on the involvement of T cells in leprosy and more recently have focused on genetic factors and innate immune response. There are still only few reports about the role of B cells in active leprosy lesions in different spectral forms of the disease. The literature on tuberculosis suggests that B cells play an important role in the regulation of the granulomas, in cytokine production, T-cell response, and antigen presentation. Only few studies investigated the role of B cell in leprosy. We investigated the distribution of B cells in 85 leprosy biopsies covering all forms of the disease and compared results with 13 biopsies of tuberculosis and atypical mycobacteriosis, expanding the previous experiences. A statistically significant difference in the number of CD20 (P = 0.014) and CD138+ (P = 0.01) cells between the different forms of leprosy was observed. A remarkable amount of CD138+ cells could also be detected in borderline tuberculoid. The median of the CD20 cells decreased from the bacilloscopy-negative samples to the bacilloscopy-positive samples by 50% (P = 0.004). Contrarily, the median of CD138+ cells showed an increase from bacilloscopy-negative to bacilloscopy-positive samples of 966.67% (P = 0.001). In our experience, tuberculoid leprosy showed more B cells and less plasma cells than lepromatous leprosy. Our results show that B cells might be implicated in leprosy pathogenesis, not only in the lepromatous pole as previously postulated, but also in tuberculoid granuloma formation and type 1 reactions.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.

The specific dermatoses of pregnancy represent a recently reclassified heterogeneous group of pruritic inflammatory skin diseases unique to pregnancy that include pemphigoid gestationis, polymorphic eruption of pregnancy (PEP), intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy (AEP). Among them, PEP and AEP are the most frequent ones. We performed a histopathological study of a series of PEP and AEP patients (n = 41). Twenty-two patients had PEP that started in the third trimester in 16 (73%) patients and postpartum in 6 (27%) patients. Histopathology revealed a superficial or superficial and deep perivascular dermatitis with eosinophils in all biopsies and signs of a lymphocytic vasculitis in 5 (23%) cases. Epidermal changes, including epidermal hyperplasia, spongiosis, and parakeratosis, occurred in 8 cases, in particular in elder lesions. Nineteen patients had AEP that started earlier [less than third trimester, 14 (74%) patients; third trimester, 5 (26%) patients]. Clinically, 5 (26%) patients showed eczematous lesions, 7 (37%) papular lesions, 3 (16%) presented both eczematous and prurigo lesions, and 4 (21%) experienced exacerbation of preexisting atopic dermatitis. Histopathologically, AEP was characterized by a perivascular lymphohistiocytic infiltrate with frequent eosinophils (74%) and epidermal changes in all but most of P-type biopsies. No definitive differential histopathological criteria between PEP and AEP were found. Only lymphocytic vasculitis with a mixed infiltrate with eosinophils was more frequent in PEP patients. Timing of onset, morphology of skin lesions, and a detailed clinicopathologic correlation are essential for diagnosis.

Phenotypic variants of mycosis fungoides (MF) include mainly the expression of cytotoxic markers by neoplastic cells (either α/β or γ/δ cytotoxic). To manage the patient properly, distinction from other cutaneous cytotoxic natural killer/T-cell lymphomas is paramount. Particularly for cutaneous γ/δ T-cell lymphoma, distinction is often based on clinicopathologic correlation (presence of tumors at first diagnosis as opposed to patches only in MF). The authors report a case of cytotoxic MF characterized by expression of TCRγ in two of three biopsies performed within a time frame of 1 week. The patient presented with patches, plaques, and 1 tumor at the time of first diagnosis; thus, distinction from cutaneous γ/δ T-cell lymphoma was not possible on clinical grounds alone. The diagnosis of MF was established, thanks to the phenotypic variations revealed by the three biopsies, with 1 lacking expression of cytotoxic proteins (TIA-1 and granzyme B) and of TCRγ. This case shows the importance to perform several biopsies in cases of cutaneous lymphoma, as morphologic and phenotypic features are variable and information gathered from a single biopsy may result in a wrong diagnosis.

Ancient melanocytic nevi are benign melanocytic neoplasms that show degenerative and atypical changes, sometimes leading to a misdiagnosis of melanoma. We describe 6 patients (M:F ratio 4:2; age range, 15-84 years; median, 50 years) who presented with cellular blue nevi showing stromal changes resembling those of ancient melanocytic nevi. The lesions were located on the buttocks (4 patients) and on the trunk (2 patients) and clinically consisted of heavily pigmented nodules. Histology revealed the architectural pattern of cellular blue nevi. However, the architecture was strikingly altered by stromal changes like those seen in ancient melanocytic nevi, including increased number of large, dilated vessels with pseudoangiomatous features in 4 cases, hyaline angiopathy in 4 cases, myxoid changes, sclerosis or hyalinization of the stroma in all cases, and variable amounts of edema in 4 cases. In 2 cases, a large edematous area was present in the center of the lesion, and nests of ovoidal melanocytes and single dendritic melanocytes appeared to "float" in the stroma. Pleomorphic melanocytes were observed in all cases. Ancient blue nevi represent a morphologic variation of cellular blue nevi-Masson neuronevi with degenerative stromal changes. Recognition of these lesions can help prevent overdiagnosis of melanoma.

Pseudolymphomas are a rare complication of vaccination, presenting with dense lymphoid infiltrates and prominent follicular pattern. We report our observations on 4 patients with vaccination-induced B-cell pseudolymphoma (all females; age range 19 to 60 years; median: 34.5 years). Clinically 3 patients presented with subcutaneous nodules and 1 presented with a large, indurated, erythematous plaque. Histology revealed in all cases dense lymphoid infiltrates in the subcutaneous fat with prominent follicular pattern. The follicles displayed features of reactive germinal centers (normal mantle zone, presence of tingible body macrophages, normal proliferation). Necrotic areas surrounded by palisaded histiocytes were seen in 3 biopsies from 2 patients. A mixed-cell infiltrate with eosinophils and plasma cells was present in all cases. In addition, histiocytes with granular basophilic cytoplasm could be observed around the focal area of necrosis or within the inflammatory infiltrate. Follow-up was available for 3 patients. One patient was alive with persistent disease 6 months after the first observation. Two patients were treated with local radiotherapy and are alive and free of disease after 12 and 72 months, respectively. One of these two patients had a second pseudolymphoma on the contralateral arm after a new injection of vaccine. Cutaneous pseudolymphoma after vaccination should be distinguished histopathologically from low-grade cutaneous B-cell lymphomas (follicle center cell lymphoma, marginal zone lymphoma) and from other B-cell pseudolymphomas with prominent follicular pattern requiring different treatment (eg, Borrelia burgdorferi-induced lymphocytoma cutis).

Telepathology is the practice of diagnostic histopathology performed on digital pictures. In this study, we focused on the technical requirements for achievement of a correct diagnosis on digital histopathologic images. A collection of 560 melanocytic lesions was selected from the files of the Department of Dermatology, Medical University of Graz, Austria. From each lesion one histologic slide was completely digitally scanned with a robotic microscope. Digital pictures were reviewed by 4 dermatopathologists using a presentation program, which recorded the number of image calls, applied magnifications, overall time needed, and amount of transmitted bits during the digital sign-out. One month later, the 4 microscopists had to review the corresponding slides and render a direct diagnosis on each case. Telepathologic diagnoses corresponded with the original diagnoses in a range from 90.4% to 96.4% of cases ([kappa] 0.80 to 0.93; P < 0.001). The median time needed for achievement of a diagnosis was 22 seconds and was significantly higher for melanomas compared with nevi. The median transmission effort for each diagnosis was 510 kilobytes after JPEG compression. Using an ISDN line with a transmission capacity of 64 kilobits/ second, this correlates to a transmission time of about 1 minute. Our results demonstrate that correct reporting on digital histopathologic images is possible with only a little time exposure. For an adequately fast transmission ISDN lines are suffcient after JPEG compression.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.

Primary cutaneous anaplastic large T-cell lymphoma (pcALCL) is a well-defined entity characterized by neoplastic cells expressing CD30, CD2, CD3, CD4, and CD5. Cases with different phenotype have been reported, including variable loss of CD2, CD3, and CD5, and expression of cytotoxic phenotype (CD8⁺) and/or of cytotoxic proteins. Aberrant phenotypes represent a diagnostic pitfall and may be the cause of misdiagnoses. We reviewed 35 cases of pcALCL (M:F = 19:16; mean age, 50.8 years; range, 14-92 years), to better characterize the immunophenotypic spectrum of the disease. Twelve cases (34%) had a T-helper phenotype (CD4⁺/CD8⁻), and TIA-1 was positive in 5 of 8 stained cases. Six cases (18%) had a T-cytotoxic phenotype (CD4⁻/CD8⁺) and were also positive for TIA-1. Positivity for both CD4 and CD8 was observed in 7 cases (20%), 4 of which were stained for TIA-1 and found to be positive, whereas both CD4 and CD8 were negative in 9 cases (26%, only 1/8 tested cases being TIA-1 positive). CD2 was positive in 21 of 27 tested cases (78%), CD3 in 21 of 34 cases (62%), and CD5 in 15 of 31 cases (48%). Interestingly, 11 cases (31%) showed a profoundly aberrant phenotype lacking simultaneously several T-cell markers. Our data allow a better characterization of pcALCL with aberrant phenotypes, showing the remarkable variability in expression of different markers.

Some cases of specific cutaneous manifestations of acute myelogenous leukemia (AML) may mimic inflammatory dermatoses both clinically and histopathologically, presenting with an inconspicuous maculopapular eruption and with only sparse dermal infiltrates. The authors studied the histopathological and immunohistochemical features of 17 biopsies from 16 patients (11 men and 5 women, age range 15-85 years) presenting with minimal skin infiltrates as the first manifestation of AML or as first sign of recurrence after complete remission of the disease. In all cases, the diagnosis of leukemia has been confirmed by bone marrow examination. Two of these cases had been sent to one of us for second expert consultation. Patients presented with generalized, exanthematic maculopapular eruptions, sometimes with a hemorrhagic note, that were mostly interpreted clinically as drug reactions. Histopathologically, the lesions showed sparse, superficial, and mid-dermal infiltrates with minimal perivascular and periadnexal accentuation. Infiltrating cells consisted mostly of neoplastic monocytoid elements with only few reactive lymphocytes and histiocytes. Immunohistochemical stainings revealed in the majority of cases positivity for CD68 (14 of 16 patients), naphthol chloroacetate esterase (NaSDCl) (7 of 10 patients), and myeloperoxidase (6 of 9 patients). Other markers tested were positive only in a minority of cases. These cases represent a pitfall both in the clinical and in the histopathological diagnosis of cutaneous AML. Accurate morphologic and phenotypic correlation together with a high index of suspicion allows a precise diagnosis in these unconventional cases.

In this study, we describe the clinicopathologic features of pseudolymphomatous infiltrates found within lesions of acrodermatitis chronica atrophicans (ACA). We studied 11 patients (10 females, 1 male, age range 60-88 years). The diagnosis of ACA in all cases was confirmed by clinicopathologic correlation and positive serology for Borrelia. Histopathologic examination revealed prominent, pseudolymphomatous inflammatory cell infiltrates in all cases, with 2 distinct patterns. Eight of 11 cases showed a band-like lymphocytic infiltrate, exocytosis of lymphocytes and a fibrotic papillary dermis, similar to features seen in mycosis fungoides. The other 3 cases showed dense, nodular-diffuse dermal infiltrates with many plasma cells and without germinal centers. The plasma cells expressed both kappa and lambda immunoglobulin light chains with a polyclonal pattern in all 3 cases. In conclusion, ACA may present with pseudolymphomatous infiltrates showing both a T-cell and, less frequently, a B-cell pattern. These lesions need to be distinguished from a cutaneous lymphoma. In the context of the knowledge of Borrelia-associated cutaneous lymphomas, follow-up seems advisable in these cases.

Leprosy is characterized by spectrum of histologically different granulomatous skin lesions that reflects the patient's immune response to Mycobacterium leprae. Presence, frequency, and distribution of both CD4+ CD25+ FoxP3+ T regulatory cells (T-regs) and CD123+ plasmacytoid dendritic cells in leprosy have never been investigated. We performed a retrospective immunohistochemical study on 20 cases of leprosy [tuberculoid tuberculoid (TT): 1 patient; borderline tuberculoid (BT): 3 patients; borderline lepromatous (BL): 5 patients; lepromatous lepromatous (LL): 5 patients; borderline borderline in reversal reaction (BB-RR): 1 patient; BT-RR: 2 patients; and erythema nodosum leprosum (ENL): 3 patients]. FoxP3-positive cells were present in 95% of the cases with an average density of 2.9% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was no statistical difference of FoxP3 expression between TT, BT, BL, and LL, whereas a statistical significant increment (P = 0.042) was observed in patients affected by reversal leprosy reactions (BT-RR and BB-RR) compared with patients affected by ENL and patients with nonreactional disease forms (BL, LL, BT, TT). CD123 expression was not observed in any of the biopsy specimens evaluated; with the exception of 2 cases of ENL, in which a focal positivity for CD123 was observed. Our results show that plasmacytoid dendritic cells are not involved in the immune response against M. leprae while T-regs are present in leprosy skin lesions. These data raise the question if T-regs have a pathogenetic role in HD as previously demonstrated in Leishmania major and Mycobacterium tuberculosis.

A new resorbable filler, Matridex, became commercially available during the last years with scarce evidence regarding side effects. A 43-year-old woman complained of multiple, painful, reddish, nonulcerated, hard nodules on both cheeks and periocular regions. Four weeks before, she had been injected by a general practitioner with Matridex for aesthetic purposes to correct wrinkles in the same areas of the nodular eruption. Histopathology showed a diffuse suppurative granulomatous reaction with the presence of multinucleate giant cells and many neutrophils involving the entire dermis. No areas of caseation were observed. The inflammatory granulomatous reaction surrounded 2 different types of nonpolarizing, bluish, exogenous material: one arranged in filamentous structures and the second composed by large spherical particles. All nodules were incised and drained; the patient received systemic antibiotic treatment for 2 consecutive weeks. The nodules progressively regressed and almost complete resolution was seen after 6 months. Matridex is a new resorbable filler constituted by a mixture of nonanimal-stabilized hyaluronic acid (HA), cross-linked HA, and dextranomer microspheres. Foreign body reactions have been described in association with other HA fillers, but a granulomatous reaction after the injection of Matridex has not been reported yet. Interestingly, in our patient, we were able to identify both fragments of HA: the filamentous particles and the spherical particles of dextranomer microspheres within the infiltrate, these last giving a characteristic and recognizable appearance to the histopathological picture.

Teledermatopathology may involve real-time transmission of images from distant locations to consulting pathologists by the remote manipulation of a robotic microscope. Alternatively, the static store-and-forward option involves the single-file transmission of subjectively preselected and captured areas of microscopic images by a referring physician. The recent introduction of virtual slide systems (VSS) involves the digitization of whole slides at high resolution thus enabling the user to view any part of the specimen at any magnification. Such technology has surmounted previous restrictions caused by the size of preselected areas and specimen sampling for telepathology. In terms of client access, these VSS may be stored on a virtual slide server, made available on the Web for remote consultation by pathologists via an integrated virtual slide client network. Despite store-and-forward teledermatopathology being the most frequently used and less expensive approach to teledermatopathology, VSS represents the future in this discipline. The recent pilot studies suggest that the use of remote expert consultants in diagnostic dermatopathology can be integrated into daily routine, teleconsultation, and teleteaching. The new technology enables rapid and reproducible diagnoses, but despite its usability, VSS is not completely feasible for teledermatopathology of inflammatory skin diseases as the performance seems to be influenced by the availability of complete clinical data. Improvements in the diagnostic facility will no doubt follow from further development of the VSS, the slide processor, and of course training in the use of virtual microscope. Undoubtedly, as technology becomes even more sophisticated in the future, VSS will overcome the present drawbacks and find its place in all facets of teledermatopathology.

A 52-year-old man was examined for an ulcerated, rapidly growing reddish nodule. It was 5.5 cm high with an 11 x 6-cm base and located on the left clavicle. The lesion had been present for approximately 7 years, and the patient complained occasional burning and pain. Clinical differential diagnoses included cutaneous lymphoma, sarcoma, squamous cell carcinoma, and cutaneous metastasis. Histopathologic examination revealed a well-circumscribed tumor involving the whole dermis and the subcutis and composed of partially confluent aggregates of matrical cells admixed with eosinophilic cornified material containing shadow cells. In addition, multinucleated giant cells, areas of calcification and metaplastic ossification, edema, and hemorrhage were also observed. On the basis of histopathologic features, the diagnosis of pilomatricoma was made. Our report highlights an unusual clinical appearance of pilomatricoma that made us consider a variety of primary or secondary cutaneous neoplasms in its differential diagnosis.