Daniela Marocolo

Histopathological changes in bone marrow biopsies from patients with chronic myeloid leukaemia after treatment with recombinant alpha-interferon

Aims: Recombinant alpha‐interferon (r‐IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r‐IFN therapy, as well as the morphological changes induced by r‐IFN within BM. Methods and results: 73 BM biopsies were studied from 21 patients with Ph1‐positive CML in chronic phase at diagnosis and at different times during r‐IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% (P = 0.02). During therapy with r‐IFN, significant BM changes included disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P = 0.0009) and total cellularity (P = 0.0027), and increase in number of terminal megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only after long‐term therapy (mean 20 months), did reticulin fibrosis increase significantly (P = 0.032). Conclusions: The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness (P = 0.025).

Nonlymphoid intraepidermal mononuclear cell collections (pseudo-Pautrier abscesses): a morphologic and immunophenotypical characterization.

We evaluated the incidence, morphology, and immunophenotype of intraepidermal collections of mononuclear cells (ICMC) in a large number of inflammatory dermatosis and cutaneous lymphomas. ICMC appeared as small to large aggregates of cells, showing a morphology variable from monocytes to obvious dendritic cells, admixed with rare lymphocytes. ICMC were recognized in the epidermis or within hair follicle epithelium, and were either loosely or compactly arranged. ICMC were identified in 124 of 1,248 skin biopsies (9.9%) of inflammatory or lymphoid infiltrates, and were particularly frequent in spongiotic (43.4%) and in lichenoid dermatitis (10%), whereas they were rarely found in nonspecific superficial dermatitis (3.8%) and in psoriasis (4.7%). ICMC were also frequent in cutaneous T-cell lymphoma (13.3%), where they mimicked Pautrier abscesses. The ICMC forming cells showed a unique phenotype: the majority of them expressed CD1a and S-100, and lacked CD14, similar to mature Langerhans cells, but they were also strongly labeled by anti-CD11b, anti-CD36, and anti-CD68. Moreover, a subpopulation of them expressed CD83, an antigen that is usually absent on Langerhans cells. The occurrence of ICMC is a rather frequent, although hitherto poorly studied, phenomenon, occurring in several dermatosis, but particularly frequent in spongiosis-associated skin reactions. The cells within ICMC are represented by dendritic cells and dendritic cell precursors, whose phenotype indicates their derivation from circulating monocytes and differentiation into mature Langerhans cells.

Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB‐1 recognizing the cell proliferation‐associated nuclear antigen Ki‐67, and antibodies against glycophorin‐C, myeloperoxidase, factor VIII‐related antigen, and immunoglobulin light chains. Fifty‐eight B5 fixed, paraffin‐embedded bone marrow biopsies were analysed, including 11 normal controls, 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non‐lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%); no Ki‐67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB‐1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB‐1+ myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non‐lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki‐67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro‐megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki‐67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki‐67 antigen and for haematopoietic cell lineage‐associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.

Dermoscopic, histological and immunohistochemical evaluation of cancerous features in acquired melanocytic nevi that have been repeatedly exposed to UVA or UVB

Abstract:  Previous studies have reported that repeated solar and artificial UVB (280–320 nm) and UVA (320–400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow‐band (NB)‐UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis‐related proteins (MART‐1, tyrosinase, HMB‐45), cell cycle activation markers (Ki‐67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia‐associated transcription factor, STAT3). Nevi that were exposed to NB‐UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB‐UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Dermatofibrosarcoma protuberans in an adolescent: a case report and review of the literature.

Classically, dermatofibrosarcoma protuberans (DFSP) is a disease of adults. The world literature revision shows that several pediatric cases have been reported so far; this might suggest that the number of infants with the condition might be larger than that estimated previously. Here, we report the 183rd case of histologically confirmed DFSP in young age. A 14-year-old white male patient came under our care for a slowly growing, pale brownish lesion on the neck skin. A biopsy specimen showed a DFSP. Subsequently, a wide surgery excision with 3 cm of resection margins including the underlying fascia was performed. To date, the patient has been in follow-up for 6 years without evidence of recurrent disease. The clinical features and treatment of DFSP diagnosed in childhood and adolescence reported in the published literature are reviewed to provide new insights about this rare entity. The aim is to emphasize the importance of biopsy for histologic evaluation in the cases that show a persistent or a large cutaneous plaque or nodule without pathognomonic clinical features that permit a clinical diagnosis. An accurate knowledge of the disease is the prerequisite for a wider recognition and appropriate treatment.

Interval Sentinel Lymph Nodes: An Unusual Localization in Patients with Cutaneous Melanoma

Background. Recent studies have demonstrated that there exists a great variation in the lymphatic drainage in patients with malignant melanoma. Some patients have drainage to lymph nodes outside of conventional nodal basins. The lymph nodes that exist between a primary melanoma and its regional nodal basin are defined “interval nodes”. Interval node occurs in a small minority of patients with forearm melanoma. We report our experience of the Melanoma Unit of University Hospital Spedali Civili Brescia, Italy. Methods. Lymphatic mapping using cutaneous lymphoscintigraphy (LS) has become a standard preoperative diagnostic procedure to locate the sentinel lymph nodes (SLNs) in cutaneous melanoma. We used LS to identify sentinel lymph nodes biopsy (SLNB) in 480 patients. Results. From over 2100 patients affected by cutaneous melanoma, we identified 2 interval nodes in 480 patients with SLNB . The melanomas were both located in the left forearm. The interval nodes were also both located in the left arm. Conclusion. The combination of preoperative LS and intraoperative hand-held gamma detecting probe plays a remarkable role in identifying these uncommon lymph node locations. Knowledge of the unusual drainage patterns will help to ensure the accuracy and the completeness of sentinel nodes identification.

Acral lympho-histiocytic dermatitis in X-linked agammaglobulinemia: a case report showing clonal CD8+ T cells with indolent clinical behaviour

gic Agonist) per day prevented the accumulation of fat and increased the energy expenditure. Fibric acids may also be useful in the treatment of BSL. This may be due to the fact that fibric acids are PRARa agonists activating the RRARa receptor suppressing the protein expression involved in the brown fat tissue architecture. Local subcutaneous injections of corticosteroids, thyroxine, enoxaparin, deoxycholate and phosphatiddylcholine have been reported but without consistently success. Benign symmetric lipomatosis, especially the abdominal variant, is less well known and can go undiagnosed for years. Masquerading as global obesity, BSL is a severe disorder leading to impairment of inner organs, skeletal structure and psyche. Improved recognition of the abdominal variant of BSL helps us to diagnose and treat patients with refractory obesity properly and prevent them from a long history of suffering.

A Case of Acrodermatitis Continua of Hallopeau Following Chronic Pustular Cheilitis

We describe the case of a young male affected by chronic pustular psoriasis of the lips that remained the only manifestation of acrodermatitis continua of Hallopeau (ACH) for years before the onset of the characteristic hand lesions.