Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases.

BACKGROUND: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. AIMS: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. MATERIALS AND METHODS: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. RESULTS: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. LIMITATIONS: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. CONCLUSION: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

[Leprosy and the testis]. / La lepra y el testículo.

INTRODUCTION: Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. MATERIAL AND METHODS: The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. RESULTS: The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. CONCLUSION: Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.

Pseudoepitheliomatous hyperplasia and transepidermal elimination in lepromatous leprosy: does T-cell plasticity play a role?

BACKGROUND: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1-predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has recently been challenged, and Cbl-b overexpression may emerge as an important factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been identified as Th1-Th2 modulators in inflammatory skin diseases, most notably psoriasis, but their roles in leprosy have not yet been elucidated. The occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal elimination of mycobacteria in LL patients, which could theoretically be a portal for contact transmission, thus raises important immunological questions: Do Th17 and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set systemically or locally? Furthermore, which microRNAs (miRs), signal transducers, and activators of transcription (STAT) proteins regulate this transition in leprosy, if any, and does differential Cb1-b expression play a role? OBSERVATION: A 71-year-old man presented with an infiltrative dermopathy characteristic of LL, as well as several hyperkeratotic plaques. Microscopic examination of the hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and transepidermal elimination of acid-fast bacilli, whereas classic histopathologic features of LL were present at other sites. HYPOTHESES: We hypothesize that: Th17 and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions, manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in LL lesions with PEH, given their association with epithelial hyperproliferation; and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions. CONCLUSION: By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to recognize these dynamic immunologic processes clinically and histopathologically and devise specific immunologic interventions.

La lepra y el testículo / Leprosy and the testis

Introducción. La afección testicular es frecuente en la lepra lepromatosa, daño que se incrementa cuando cursa con eritema nudoso leproso. Objetivo. Presentar un paciente con lepra lepromatosa y eritema nudoso leproso con grave compromiso testicular. Materiales y métodos. Se estudió un hombre de 28 años con lepra lepromatosa desde los 22, que durante la poliquimioterapia para la lepra presentó eritema nudoso leproso crónico que afectó ambos testículos y no respondió al manejo convencional. El dolor persistente obligó a practicar orquidectomía izquierda. Resultados. Este testículo presentaba atrofia tubular y fibrosis notorias, conglomerados de macrófagos espumosos, sin bacilos, hiperplasia focal de células de Leydig, endarteritis y arteritis linfocitaria y granulomatosa de vasos pequeños y medianos; estos cambios también estaban presentes en el epidídimo. Un estudio llevado a cabo dos años después de terminar su tratamiento y de la orquidectomía izquierda, demostró azoospermia, testosterona total normal, testosterona libre discretamente disminuida y hormonas lutropina (luteinizante) y folitropina (estimulante del folículo) elevadas. No había disminución de la libido ni de su actividad sexual. Se revisaron los conceptos generales sobre el eritema nudoso leproso y las alteraciones que la lepra produce en el testículo. Conclusión. La lepra lepromatosa puede conducir a hipogonadismo. Los programas de lepra deben contemplar esta complicación para corregir y evitar sus secuelas.

Introduction. Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. Material and methods. The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. Results. The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. Conclusion. Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.

Pigmented trichoblastoma with sebaceous hyperplasia.

Trichoblastoma is a rare benign trichogenic tumour with epithelial and mesenchymal components recapitulating the germinal hair bulb and associated mesenchyme. A 50- year- old male patient presented with slowly enlarging circumscribed solid nodule measuring 4x3x4.5 cm over the tip of the nose. Microscopy of tumour revealed nodular tumour spanning the entire dermis with collection of mesenchymal cells resembling follicular papilla. Areas of pigmentation and sebaceous hyperplasia were noted. There is a need for differentiation of this tumor which is benign, from other pigmented tumors having basaloid arrangement of cells such as basal cell carcinoma.

Anti-inflammatory activity of superoxide dismutase obtained from Debaryomyces hansenii on type II collagen induced arthritis in rats.

INTRODUCTION: Rheumatoid arthritis is an autoimmune inflammatory disease of unknown etiology, free radicals have been implicated in the genesis and perpetuation of damage in this pathology. OBJECTIVE: To evaluate the anti-inflammatory effect of Cu,Zn-superoxide dismutase (SOD) obtained from two different sources (bovine erythrocytes, Be-SOD, and Debaryomyces hansenii, Dh-SOD) with Type II Collagen-induced Arthritis model in rats. MATERIAL AND METHODS: Arthritis was induced by repeated injection of a porcine type II collagen-incomplete Freund adjuvant suspension on the back of Dark Augui (DA) rats. Arthritis was clinically evaluated throughout the study. Body weight was determined at three different times. Two different doses for each treatment (Be-SOD, Dh-SOD) were tested: 100 and 1,000 U/kg. At the end of the trial (day 28), histological analyses of the most inflamed ankle joint, as well as serum anti-collagen antibodies, were determined. RESULTS: Both sources of SOD decreased, although to a different extent, the incidence and severity of the disease. Arthritis score was lower in all treatments, except for the low dose of Be-SOD. Groups receiving either source of SOD showed a significant weight increase compared to the placebo group. Histological damage was similar in all groups. Only the group that received the highest dose of Dh-SOD showed a significant lower antibody titer; nevertheless, no correlation appears to derive from arthritis score and antibody titer. CONCLUSION: Our findings suggest that, although unable to counteract the arthritis syndrome, SOD may still be beneficial due to its anti-inflammatory activity. In the case of Dh-SOD, the best effect was observed at the highest dose tested.

Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness.

Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.p. injection and then challenged by OVA inhalation. Hsp were administered to each group by i.p. injection before sensitization and challenge. Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals. Administration of M. leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner. Treatment with M. leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-gamma production were increased. Furthermore, M. leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction. In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production. Depletion of gamma/delta T lymphocytes before sensitization and challenge abolished the effect of M. leprae hsp treatment on AHR. These results indicate selective and distinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Pseudoepitheliomatous hyperplasia in trophic ulcers in leprosy patients. A 28-case study.

Between 1984 and 1993, pseudoepitheliomatous hyperplasia developing in chronic ulcers were observed in 28 former Senegalese leprosy patients, which amounts to an annual frequency of 1.9 per 1000 ulcers. Correct diagnosis could only be made by histopathological examination of specimens taken from the depth of the lesion. Amputation was carried out on 17 patients and local excision on the other 10. Recurrence of growth was observed in 8 of the 10 patients treated by excision; in all of these 8 cases below knee amputation had to be subsequently performed. From our experience, it may be assumed that local excision should be carried out only in the case of small tumours. Since the aim of surgical procedure is to allow the patient to have physical autonomy, below knee amputation, followed by adaptation of prosthesis, should be the procedure chosen in the other cases.

[Tumoral proliferations in chronic plantar ulcers: how to treat?]. / Proliférations tumorales développées sur maux perforants plantaires: quelle attitude thérapeutique?

Between 1983 and 1994, 66 Senegalese leprosy patients were seen for cauliflower growths developed in chronic plantar ulcer (CPU), (2 patients had each 2 tumors). 68 biopsies for pathological examination were taken: the diagnosis of squamous cell carcinoma was effectively made in 39 cases (38 patients) and that of pseudo-epitheliomatous hyperplasia in the remaining 29 cases (28 patients). The mean annual frequency of cauliflower growths was 0.45 per 100 CPU. Among these tumors, the percentage of carcinoma was 57%. Of the 38 patients with a carcinoma, 5 refused amputation and all of them died. The 33 others were amputated and of these 8 died as a direct result of their carcinoma (24%). In the case of the 28 patients with hyperplasia, amputation was carried out on 18 patients and local excision on 10. In the months following the operation 8 recurrences were observed in 10 of the patients on whom excision had been carried out. These recurrences were treated by amputation. This gives a total of 93% of amputations in the cases of hyperplasia. These facts lead as to conclude that at least in countries where pathological examination is not available below knee amputation is the most reasonable action to take in the proliferative tumors developed on a CPU.

[Characterization of chronic plantar ulcers in former leprosy patients]. / Cancérisation des plaies chroniques plantaires chez les anciens malades de la lèpre.

Between 1988 and 1992, 21 biopsies for pathological examination were taken from 20 Senegalese leprosy patients suffering from chronic plantar ulcers (CPU) suspected of malignant transformation. The diagnosis of squamous cell carcinoma was effectively made in 13 cases and that of pseudoepitheliomatous hyperplasia in the remaining 8 cases. The mean period of time between the onset of CPU and that of malignant transformation was 10 years (range: 1 to 15 years); the mean annual frequency of the malignant transformation was 2 per 1,000 CPU. In countries where pathological examination is not available, below knee amputation could be considered whenever main clinical signs of malignant transformation are present. In countries where pathological examination is available, the therapeutic decision may differ according to the diagnosis: below knee amputation supplemented with block dissection of inguinal lymph nodes whenever possible in cases of carcinoma; below knee amputation depending on the function status of the foot and on the volume of tumor in case of pseudo-epitheliomatous hyperplasia.

Malignant transformation of plantar ulcers in leprosy.

Malignant transformation of plantar ulcers in leprosy is not uncommon. The apparent rarity of these neoplasms could be because many observed cases are not reported. To determine the extent of the problem, 133 consecutive cases of plantar ulcers seen over two years were studied clinically as well as histologically. Plantar ulcers were more common in the distal third of foot (64.67%) but malignant transformation was seen more often in plantar ulcers of proximal third of foot (64.29%). Malignant transformation was more common in plantar ulcers of long duration. Histologically, most of the lesions were benign, being instances of pseudo-epitheliomatous hyperplasia (57.89%) or atypical pseudo-epitheliomatous hyperplasia (13.53%). However, squamous cell carcinoma was observed in 10.53% cases. Thus it may be that more cases with this complication will be detected if it is borne in mind that malignant change may be encountered in such ulcers.

Bone marrow cyto-morphological changes in multibacillary leprosy.

Seventy-two cases of multibacillary leprosy were investigated for cytomorphological changes and presence of lepra bacilli in bone marrow. These patients were divided in two groups. Group A (28) comprised of new cases and group B (44) of those receiving treatment. Myeloid hyperplasia was mostly seen in patients of group B who had erythema nodosum leprosum. Megaloblastic change in erythroblasts was seen frequently in both the groups. While average number of plasma cells and macrophages was on the higher side of normal range, detection of large number of plasma cells underlined enhanced humoral response and created diagnostic problem with multiple myeloma. Morphological changes in the macrophages, their collections and epithelioid cell granulomas were observed in bone marrow. Their nature and significance is discussed.