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.

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

MIGNOGNA, MICHELE DAVIDE;FORTUNA, GIULIO;FALLETI, JESSICA;LEUCI, STEFANIA
2009

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/375744
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