Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: We studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: The mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: The mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Store-independent Orai1-mediated Ca2+ entry and cancer.

Ca2+ channels play an important role in the development of different types of cancer, and considerable progress has been made to understand the pathophysiological mechanisms underlying the role of Ca2+ influx in the development of different cancer hallmarks. Orai1 is among the most ubiquitous and multifunctional Ca2+ channels. Orai1 mediates the highly Ca2+-selective Ca2+ release-activated current (ICRAC) and participates in the less Ca2+-selective store-operated current (ISOC), along with STIM1 or STIM1 and TRPC1, respectively. Furthermore, Orai1 contributes to a variety of store-independent Ca2+ influx mechanisms, including the arachidonate-regulated Ca2+ current, together with Orai3 and the plasma membrane resident pool of STIM1, as well as the constitutive Ca2+ influx processes activated by the secretory pathway Ca2+-ATPase-2 (SPCA2) or supported by physical and functional interaction with the small conductance Ca2+-activated K+ channel 3 (SK3) or the voltage-dependent Kv10.1 channel. This review summarizes the current knowledge concerning the store-independent mechanisms of Ca2+ influx activation through Orai1 channels and their role in the development of different cancer features.

[Synchronous metastases of the spermatic cord from papillary renal cell carcinoma]. / Carcinoma renal papilar con metástasis sincr6nica en el cordón espermático.

Papillary renal cell carcinoma has been related with higher survival rate and lower metastatic cancer mortality rate than clear renal cell carcinoma. We present an aggressive case related to unusual features for this histological type, like a tumor size higher than ten cm, great perirrenal fat and suprarenal gland infiltration, tumoral thrombosis of the infrahepatic cava vein, retroperitoneal adenopatic tumoral infiltration, high nuclear grade and synchronous solitary distant organ metastases of the right spermatic cord, finding three previous cases in the literature with this last feature. Prognostic implication of the papillary renal cell carcinoma type is unclear in cases like this, so probably we need better molecular and cytogenetic studies to get a correct classification of this histological type.

[Primary hepatic actinomycosis]. / Actinomicosis hepática primaria.

Primary hepatic actinomycosis is a rare infection that can clinically be confused with hepatic pyogenous abscesses or neoproliferative processes. We present the case of a 71-year-old man who had previously undergone total gastrectomy for gastric adenocarcinoma. After 4 years of favorable clinical course he presented a space-occupying lesion in the right hepatic lobe. Diagnostic tests were nonspecific and the diagnosis was confirmed by histological study of a biopsy of the lesion obtained through laparotomy. Prolonged antibiotic treatment produced a complete response. The etiopathogenesis and diagnostic-therapeutic options of hepatic actinomycosis are reviewed.

Splenic and adrenal lymphangiomatosis.

Lymphangiomatosis is a rare syndrome that can affect different organs, although simultaneous splenic and adrenal involvement is exceptional. We report the case of a young female with a symptomatic massive splenomegaly and no-nhypersecreating bilateral adrenal masses incidentally discovered that represented a diagnostic challenge. The management of adrenal incidentalomas is controversial, as the presence of large sized bilateral masses are highly indicative of malignancy. Despite the different diagnostic techniques available, it is sometimes impossible to reach an accurate preoperative diagnosis. Elective splenectomy and left adrenalectomy were performed, preserving the functioning of the right adrenal gland, radiologically similar to the left one, to prevent the development of definitive adrenal insufficiency. Postoperative evolution has been favourable without initial increase of the size of the right adrenal lesion. However, the persistence of this mass obligated long-term follow-up and shall assist us in better understanding the behavior of this bening lesion.

Massive ovarian oedema.

Eighteen cases of massive ovarian oedema are presented. The age of patients averaged 26 years and 16 presented with an acute abdomen. Hormonal symptoms included virilism in three cases and one with precocious pseudopuberty. Ultrasonographic findings were variable and not diagnostically accurate. When performed, CA 125 levels were not raised. Seventy-two percent of cases occurred in the right ovary and none were bilateral. Torsion occurred in 14 cases. Salpingo-oophorectomy was performed in all cases. To elucidate its pathogenesis, be this either due to intermittent chronic torsion or to a proliferative phenomenon, immunohistochemistry for Ki-67 and PCNA proliferation antigens, alpha-actin and oestrogen and progesterone receptors was performed. The Ki-67 proliferation index ranged between 0% and 3%, demonstrating the low proliferative status of stromal cells. The PCNA indices, however, were unusually high (60% and above). The divergence between these findings is explained by the fact that PCNA positivity may be related to nuclear reparation subsequent to ischaemia. Alpha-actin was consistently positive in stromal cells, reflecting a myofibroblastic transformation of these cells. These findings together with the clinical evidence of torsion in the majority of cases, lead us to consider that ovarian oedema is a reactive, non-proliferative state of specific stromal cells, occurring as a response to torsion and subsequent ischaemia. The stromal cells have positive oestrogen progesterone receptors and may undergo stimulatory changes responsible for the hormonally related symptoms often found associated with massive ovarian oedema.

[Solitary extramedullary plasmocytoma of the nasal fossa and paranasal sinuses]. / Plasmocitomas solitarios extramedulares de fosas nasales y senos paranasales.

The clinical and morphological features of two patients with solitary extramedullary plasmacytomas of paranasal sinus and nasal cavity are presented. Patients only developed local symptomatology without features of multiple myeloma. They were treated with surgical excision and local radiotherapy. This is the treatment of choice recommended for these localized tumors. Microscopically, one tumor contained a well-differentiated plasma cell population, and the other was made up immature cells. Cytoplasmic staining for IgG was showed in both tumors for immunoperoxidase studies. However, no serum monoclone was detected at the time of diagnosis nor later. Currently, they are alive without evidence of disease 20 and 16 months, respectively, after treatment.

[Rhinosporidiosis: presentation of 4 cases]. / Rinosporidiosis: aportación de cuatro casos.

We report 4 cases of rhinosporidiosis in the province of Cáceres. Two had nasal localization and in two ocular conjunctiva was involved. Three patients, two of which came from the same village, had the antecedent of bathing in the same stagnant water. The diagnosis was made by the microscopic observation of characteristic sporangia of Rhinosporidium seeberi in the histopathological study. The lesions did not respond to antibiotic and antiinflammatory treatment. After excision there were no recurrences, and the patients are asymptomatic after 1 1/2 year follow up.