Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients.

BACKGROUND: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS: This was a case series retrospective study. CONCLUSION: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.

Primary cutaneous diffuse large B-cell lymphoma, leg type and secondary cutaneous involvement by testicular B-cell lymphoma share identical clinicopathological and immunophenotypical features.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg type can eventually disseminate to extracutaneous sites including testes. In addition, patients with testicular lymphoma can develop specific skin involvement. OBJECTIVE: We sought to describe similarities between PCDLBCL, leg type and testicular B-cell lymphoma affecting the skin. METHODS: We report two cases with typical clinicopathological and immunophenotypical features of leg type lymphoma occurring simultaneously with a testicular B-cell lymphoma. We also report an additional case of PCDLBCL, leg type with secondary testicular involvement. RESULTS: All cases presented with typical red tumors exclusively located on the legs. Histologically, all cases showed a diffuse nonepidermotropic infiltrate composed of large blastic cells mainly centroblastic type. Phenotype showed strong positivity for Bcl-2, MUM-1, and FOXP1. Epstein-Barr virus stains and CD30 were negative in the 3 cases. In all cases the testicular infiltration showed the same pathological and phenotypical changes to those observed in the skin. LIMITATIONS: This was a retrospective case series study. CONCLUSION: Skin involvement by testicular B-cell lymphomas and PCDLBCL, leg type are indistinguishable on the basis of pathologic and immunophenotypical features, therefore specific investigation and clinic correlation are needed.

Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours.

BACKGROUND: Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain. OBJECTIVE: To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases. METHODS: Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs. RESULTS: TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC. CONCLUSIONS: In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases.

BACKGROUND: The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon. OBJECTIVE: This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component. PATIENTS AND METHODS: The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30(+) cutaneous T-cell lymphoma (2 patients), CD4(+) small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed. RESULTS: The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established. CONCLUSION: The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Discussion on the indication of allogeneic stem cell transplantation for advanced cutaneous T cell lymphomas.

Advanced cutaneous T cell lymphoma (CTCL) patients have a dismal prognosis, especially those relapsing or progressing after systemic therapy. No curative therapies are available, but some new agents have prolonged disease-free survival time with a good toxicity profile. Allogeneic stem cell transplantation (allo-SCT) offers the longest disease-free survival, potentially representing the best therapeutic option for eligible patients. In the present article, we discuss current evidence about allo-SCT for CTCL patients, timing, and new therapeutic options before allo-SCT, taking into account some considerations that may impact clinical outcome.

Bullous pemphigoid and multiple sclerosis: a report of two cases with ELISA test.

We report two patients with longstanding multiple sclerosis (MS) who developed vesicles and bullae consistent with the diagnosis of bullous pemphigoid (BP). Both patients showed linear IgG at the dermal-epidermal junction, located on the epidermal side of patients' skin previously treated with 1M NaCl. In the two cases, the ELISA test was positive for the extracellular fragment of BP 180. However, the indirect immunofluorescence test (IIF) was repeatedly negative. Therapy either with prednisone plus dapsone or prednisone alone was initiated and the disease was controlled after 23 and 15 months of therapy, in patients 1 and 2, respectively. However, the first patient had a flare-up 2 months after treatment was stopped. The association of MS and BP has been described previously in 35 cases. We compare our two cases with the 25 patients previously reported in detail in the literature. We emphasize the role of the ELISA test in establishing the diagnosis of BP.

Annually recurring erythema annulare centrifugum: a distinct entity?

Four patients presenting a peculiar clinical variant of erythema annulare centrifugum are reported. The lesions were clinically and histopathologically indistinguishable from classic superficial erythema annulare centrifugum but constant annual and seasonal recurrences for many years or decades were observed. No clear precipitating factor could be identified. No associated symptoms were present and the eruption regressed spontaneously after a variable period of days to months. Annually recurring erythema annulare centrifugum seems to represent a rare distinct clinical entity that has received little attention in literature. Clinicopathologic features of this peculiar clinical disorder and the differential diagnosis with other recurrent seasonal eruptions are reviewed.

Peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement: a clinicopathologic study of four cases.

Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.

Familial leiomyomatosis cutis et uteri (Reed's syndrome).

We report a large family with leiomyomatosis cutis et uteri. Sixty-four percent of the females were involved; 18% had only uterine myomas, 10% had only cutaneous piloleiomyomas, and 36% had both. Five patients (45%) had to have an hysterectomy before age 35. Management of female patients having leiomyomatosis cutis should include a periodical gynecological examination in order to rule out the presence of uterine myomas.

[Multiple and unilateral angiofibromas of the face: forme fruste of Bourneville tuberous sclerosis]. / Angiofibromes multiples et unilatéraux de la face: forme fruste de la sclérose tubéreuse de Bourneville.

BACKGROUND: Multiple facial angiofibromas are considered a characteristic and pathognomonic feature of tuberous sclerosis. In contrast, the observation of localized multiple angiofibromas limited to one side of the face is a uncommon. OBSERVATIONS: We cared for two patients with multiple clustered unilateral angiofibromas (although one patient also presented a few angiofibromas on the other side) without other features associated with the sclerosis tuberous complex. DISCUSSION: The possibility that these patients presented an independent disorder or a minor form of tuberous sclerosis is discussed.

[Non-congenital smooth muscle hamartoma: 3 cases]. / Hamartome musculaire lisse non-congénital: 3 cas.

BACKGROUND: Smooth-muscle hamartoma is an uncommon, usually congenital cutaneous hyperplasia of the arrectores pilorum muscles. When it is acquired, it may be confused with Becker's nevus with a prominent smooth-muscle component. Both entities can be considered polar forms of a spectrum of dermal smooth muscle hyperplasia. We report three cases of acquired smooth-muscle hamartoma in adult patients. CASE REPORTS: Three healthy women in their fifties presented with adult-onset asymptomatic, multiple small papules grouped on circumscribed areas of the trunk. Results of biopsy specimens showed an excess of haphazardly oriented smooth-muscle bundles in the mid to lower dermis with an unremarkable overlying epidermis. Immunohistochemical studies showed two components in this proliferation: a smooth muscle cell population expressing vimentin and smooth muscle actin, and another population of CD34 positive dendritic cells, interspersed among the former. DISCUSSION: Proliferation of CD34+ dermal dendritic cells has been recently described as an additional component in the proliferation of smooth muscle cells, hair follicles and nerve fascicles that constitute congenital smooth muscle hamartomas. The results of immunohistochemical studies in our three cases extend this observation to the acquired variant of cutaneous smooth muscle hamartoma, which can be included in the expanding spectrum of diseases, recently characterized by the presence of a dermal proliferation of CD34 + cells.

[Congenital spontaneously regressive cutaneous Langerhans cell histiocytosis with bone involvement (eosinophilic granuloma)]. / Histiocytose langerhansienne congénitale cutanée auto-involutive avec atteinte osseuse (granulome éosinophile).

INTRODUCTION: The classification of Langerhans' cell histiocytosis into 5 forms does not cover all types of clinical presentations. We observed a patient with inborn Langerhans' cell histiocytosis involving the skin and bone tissue. The clinical course was benign during the first two years of the patient's life. CASE REPORT: Skin lesions noted at birth resolved spontaneously but recurred twice in a more benign form. Histology examination showed "band" infiltration of the papillary derma composed of Langerhans' cells in direct contact with the basal epidermal layer and a few eosinophils. Immunolabelling was intensely positive for protein S100 confirming the diagnosis of Langerhans' cell histiocytosis. Extension was limited to a lytic lesion in the lower part of the left tibia which was treated by curettage. DISCUSSION: In our opinion, Langerhans' cell histiocytosis covers a wide range of clinical presentations. Our case was remarkable because of the benign course despite its congenital nature and dissemination to skin and bone. Prolonged surveillance of Langerhans' cell histiocytosis is required for patients without any apparent prognosis factors.