Angiosarcoma Mimicking Rhinophyma

We report the case of a 61-year-old man showing persistent erythematous macules, plaques, and partially confluent nodules with irregular borders, developed on his nose for one year. During that time the patient underwent several dermatological consultations, and all produced the same diagnosis: rhinophyma. So antibiotic and steroid treatment was carried out without any improvement while the lesions kept growing. When the patient came to our observation, physical examination revealed large, infiltrative, oedematous, erythematous plaques and rare nodules, with superficial telangiectatic vessels. Cervical lymphadenopathy was not detectable. Routine laboratory analysis was normal. Punch biopsy was performed, and histopathology and immunohistochemical studies were consistent with cutaneous angiosarcoma. This is the report of a face angiosarcoma with an unusual and very deceptive clinical presentation

First report of Stephanostomum cesticillus (Molin, 1858) Looss, 1899 in Merluccius merluccius (Linnaeus, 1758) from the Tyrrhenian Sea (Southern Italy)

The genus Stephanostomum consists of digenean trematodes found in many marine teleosts. In this study, Stephanostomum cesticillus (Molin, 1858) Looss, 1899 metacercariae were identified in European hake (Merluccius merluccius, Linnaeus, 1758) caught in the Tyrrhenian Sea. The metacercariae were found encapsulated in the muscle, close to the spine and gills. Out of 131 specimens, 111 (P = 84.7%, mI = 25.1 mA = 21.3) were infected by digenean trematode metacercariae. Morphological and histological evaluations were carried out. The members of this genus are characterised by a double crown of spines close to the oral sucker. For identification of the parasite, molecular analysis was performed via 28S and 18S ribosomal DNA (rDNA) genes. Partial rDNA sequences of Stephanostomum highly matched to S. cesticillus for the percentage of similar identity from the nucleotide database of BLAST. The present survey reports the presence of S. cesticillus metacercariae in M. merluccius for the first time. Our results improve current knowledge on hake parasites to better understand the distribution of S. cesticillus in M. merluccius caught in the Mediterranean Sea and shed light on the life cycle of the parasite adding other possible hosts

IGH FISH DNA PROBE NEI PROCESSI LINFOPROLIFERATIVI B CELLULARI CUTANEI

I linfomi cutanei primitivi sono un gruppo eterogeneo di disordini che originano da cellule linfoidi T e B della cute senza alcuna evidenzia di malattia extracutanea al momento della diagnosi e nei sei mesi successivi. Tuttavia, così come in altri distretti, non tutti processi linfoproliferativi cutanei sono maligni, ma possono esistere delle forme benigne di iperplasia linfoide con o senza atipie che mimano i processi maligni e che non necessitano di nessuna terapia. I criteri per distinguere tra una iperplasia linfoide ed un linfoma B-cellulare di basso grado non sono ben definiti; la diagnosi di un processo linfoproliferativo cutaneo resta attualmente una delle maggiori difficoltà in dermatopatologia poiché le sole caratteristiche citomorfologiche sono insufficienti per la diagnosi. La morfologia, quindi, deve essere necessariamente integrata con le caratteristiche immunofenotipiche e citogenetiche. L’identificazione della clonalità in un infiltrato cellulare linfoide, in un appropriata presentazione clinica, dovrebbe far porre una diagnosi di linfoma. L’applicazione di tecniche di immunocitochimica ed analisi molecolare ha mostrato che alcuni casi classificati come iperplasia linfoide o pseudolinfoma contengono una popolazione monoclonale B cellulare e che quindi sono stati successivamente considerati veri linfomi e viceversa. Il locus della catena pesante IgH delle immunoglobuline umane è situato sul cromosoma 14q32 ed è coinvolto in diverse traslocazioni con partner cromosomici specifici in numerosi linfomi non Hodgkin (LNH). La sonda IgH FISH DNA con segnale di split è composta da due fluorocromi coniugati a due filamenti di DNA: un filamento, coniugato a fluoresceina verde, lega il segmento telomerico di 612 Kb fino al breakpoint; il secondo, coniugato a Texas Red, lega il segmento centromerico di 460 Kb fino al breakpoint. Quando il gene è integro, la sonda genera un segnale di fusione; in caso di traslocazione la sonda genera due segnali distinti (split signal) verde e rosso. Pertanto la sonda dovrebbe identificare qualsiasi punto di rottura che coinvolga il locus IgH valutando la clonalità del corrispondente processo linfoproliferativo indipendentemente dal partner coinvolto e da uno specifico sottotipo. Scopo dello studio: valutare l’efficacia della sonda IgH FISH DNA probe nella diagnosi di processi linfoproliferativi B cellulari su biopsie cutanee. Sono stati selezionati 20 casi, in particolare: 7 linfomi non-Hodgkin B-cellulari , 12 casi di iperplasia linfoide atipica B-cellulare (sia più probabilmente reattiva e sia possibile espressione di linfoma di basso grado) ed uno pseudolinfoma da Leishmaniosi cutanea. La nostra serie è costituita da 20 pazienti di cui 13 di sesso femminile e 7 di sesso maschile, con range di età compreso tra 6 e 76 anni con età media di 51.2 anni. Le biopsie sono state effettuate in diversi distretti cutanei e, nello specifico, tutte da lesioni cutanee singole in assenza di coinvolgimento linfonodale e/o sistemico. Per ogni caso sono stati contati un totale di 200 nuclei; il segnale era considerato “vero” se il nucleo era intatto e non sovrapposto ad altri. E’stato considerato positivo un segnale di split ≥ 10%, e negativo un segnale di split < 10%. I risultati ottenuti sono stati correlati con metodiche di biologia molecolare ed integrati con i dati clinici: nello specifico la sonda ha dimostrato il segnale di split nei casi diagnosticati come franco linfoma e negli unici due ove, essendo disponibile il follow-up, si evidenzia la progressione in linfoma. Tali dati ci permettono di dire che la sonda IGH FISH DNA segnale di split ha mostrato una elevata sensibilità per il riconoscimento della clonalità nei disordini linfoproliferativi cutanei valutata su campioni di biopsie cutanee: Questo risultato deve essere considerato “promettente” ed un buon punto di partenza per valutare l’applicabilità della sonda in rapporto alla PCR e, specificamente all’area grigia dell’ iperplasia linfoide atipica B-cellulare, su una casistica certamente più ampia e con un buon follow-up

Gastric diffuse large B-cell lymphoma (DLBCL) exhibiting oral acanthosis nigricans and tripe palms

Approximately one-third of non-Hodgkin lymphomas arise primarily from sites other than lymph nodes, such as spleen or bone marrow, and even from sites which normally contain no native lymphoid tissue. The extranodal lymphomas represent a challenge in routine lymphoma diagnosis, due to the variety of histological types, molecular abnormalities and clinical pictures [1]. Diffuse large B-cell lymphoma (DLBCL) is the most common extranodal lymphoma encountered in the gastrointestinal tract. This is mainly a disease of older adults in the seventh decade, even though it may occasionally affect children and young adults. It typically produces large, destructive lesions that may invade adjacent structures [2]. A 74-year-old woman was referred to our Oral Medicine Unit by the nearby Cardio-pulmonary Unit, where she was hospitalised because of severe pneumonia refractory to the antibiotic therapy. Here, routine haematological blood tests revealed lymphocytosis, mild anemia, and a slightly elevated lactate dehydrogenase, whereas a basic workup for underlying malignancy was normal, except for a mild increase of beta2-microglubulin. Clinically, diffuse micropapillary lesions on the hard palate and inner upper lips (Fig. 1A), a “cerebriform” aspect of the right cheek (Fig. 1B), and a velvety rugose appearance on palms and palmar surface of the fingers on both hands (tripe palms) (Fig. 1C and D) were detected. Oral biopsy revealed amarked epithelial thickening with papillary hyperplasia, acanthosis, and slight dyskeratosis. The dermal papillae project upward as finger-like projections with a chronic lymphomonocytic inflammatory infiltrate (Fig. 1E). Oral acanthosis nigricans (AN) associated with tripe palms was suspected. Benign AN was excluded, because no associated syndrome, obesity, or medical history of taking medicine was found. The glycosylated haemoglobin level and insulin resistant testswere normal. Conversely, malignant AN was confirmed by the presence of a hyperplastic nodular mass, with a superficial erosion, on the wall of the stomach. A biopsy revealed features consistent with DLBCL, showing a lymphoid infiltrate in the lamina propria with a predominance of small to medium-sized and scattered large cells (Fig. 1F), which turned out to be CD 20 positive (Fig. 1G), invaded and destroyed the glandular epithelium that was pancytokeratin positive (Fig. 1H). The stagewas EI2, according to theAnnArbor classificationmodified by Musshoff [3], since a total body CT scan did not detect any enlarged lymph nodes. The CT scan and tumour markers were re-performed 1 month later, some days before her demise, with negative results, as sometimes the primary tumour might not be detected for a long time [4]. Thus, no other malignancy was detected, reinforcing the association between gastric DLBCL and malignant AN. The patient died due to severe cardio-pulmonary complications. AN is a rare mucocutaneous disorder, which is characterised by cutaneous and oral papillary lesions [5]. It includes a benign and a malignant form, which is associated with an underlying, often aggressive, malignancy, either non-haematological [5] or haematological [6]. The pathogenesis of malignant AN is still unclear. A possible mechanism might involve the production of the transforming growth factor alpha (TGF-), which is closely related to the epidermal growth factor (EGF) and binds to the same receptor, EGFR. This binding activates the classical mitogen-activated protein kinase (MAPK, ERK) pathway, involved in regulating basic cellular functions such as proliferation, differentiation, and migration [7]. Since some type of cancers produce large amounts of TGF-, it is likely that keratinocyte growth might be stimulated via an endocrine route.Whether this pathogenetic mechanism might also be applied to the DLBCL remains questionable and, thus, further investigations are required

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

Capecitabine is an oral prodrug that is converted to its only active metabolite, Fluorouracile (5-FU), which has been used for numerous types of neoplasms, such as breast, esophagus, larynx cancer and, also, for the treatment of metastatic breast cancer as either a single agent or in combination with docetaxel after failure of prior anthracycline-based chemotherapy.1 Recently, FDA approved the combination of Capecitabine and Lapatinib for the treatment of advanced or metastatic breast cancer, overexpressing human epidermal growth factor receptor (HER)-2.2 A 61 year-old female patient with breast cancer, received right mastectomy, homolateral axillary lymphoadenectomy, and radiotherapy, entering in remission. After seven years, due to the metastatic progression of the disease, she received radiotherapy and anthracycline-based chemotherapy, obtaining partial results. Thus, it was administered Lapatinib (1,250 mg PO qd) continuously plus Capecitabine (2,000 mg/m2 PO qd) for a 14 days cycle with 7 days off,3 and, concurrently, Zolendronic acid (4 mg IV monthly) and lansoprazole (15 mg PO qd). During the third cycle she developed a mild palmar-plantar rash that disappeared spontaneously within 24 hours. During the fourth cycle she developed a persistent and painful bullous and lichenoid mucositis localized on the anterior third of the tongue (Fig. 1a), that showed a positive Nikolsky’s sign, as well as erythematous areas on the checks bilaterally (Fig. 1b), accompanied by a severe hand-foot syndrome (HFS). Due to these grade 3 side effects, patient was dechallenge and rechallenge for a fifth cycle at a dosage of Capecitabine adjusted to 50%. 4 Oral lesions disappeared, while HFS presented with a milder clinical aspect. She was not definitively dechallenge, because the discomfort of skin lesions did not interfere with her normal daily activities and quality of life. Oral biopsy revealed hyperparakeratosis, focal hypogranulosis, intraepithelial necrotic keratinocytes, some angiectasic vessels in the lamina propria with focal lymphomonocytic infiltrate (Fig 1c and 1d). Direct immunofluorescence, indirect imunofluorescence, immunoblotting and ELISA tests for Desmoglein 1 and 3, for BP230 and BP180 were negative. These essays allowed us to exclude a paraneoplastic and/or drug-induced autoimmune disease. The Naranjo Adverse Drug Reaction (ADR) Probability Scale showed that Capecitabine was a “probable” cause of HFSS and oral mucositis, given a score of 6 (Table 1).5 No other side effect or hematological abnormalities, except for a mild anemia and neutropenia, was detected. As the dosage of Lapatinib was maintained constant, while the dosage of Capecitabine was reduced, a diagnosis of Capecitabine-induced bullous and lichenoid stomatitis was made

Gastric Duplication Cyst: A Rare Congenital Disease Often Misdiagnosed in Adults

Gastrointestinal duplication is a rare congenital disease which affected more commonly the ileum, while the stomach is rarely involved. Generally diagnosed in paediatric or young age, it could be difficult to suspect a gastrointestinal duplication in adults. Herein, we report a 55-year-old male with a gastric duplication cyst found on routinely checkup for chronic hepatitis and first misdiagnosed as a gastrointestinal stromal tumor (GIST); we also discuss its embryology

Acinic Cell Carcinoma of the Breast Arising in Microglandular Adenosis

Acinic cell carcinoma is a rare breast tumour belonging to salivary gland-like tumours of the breast. They are “triple-negative” breast cancers even if their biological behaviour seems to be more favourable. Herein we present an acinic cell carcinoma arising on a background of typical and atypical microglandular adenosis in a 58-year-old woman, along with a review of the literature