The Diagnostic Utility of Calretinin in Deep Fibromatosis when Dilemma of Spindle Cell Mimic Lesions are Considered: An Immunohistochemical Study

Nuclear beta catenin is a well known diagnostic marker for fibromatosis but with limited specificity and frequent background stain. Calretinin is an intracellular calcium binding protein that is found to be expressed in many cell types. The study included 20 desmoid cases (abdominal wall fibromatosis) along with 7 cases of intra-abdominal mesenteric fibromatosis and other spindle cell lesions including 11 MPNST (malignant peripheral nerve sheath tumor) cases, 15 cases LMS (leiomyosarcoma), 5 cases synovial sarcoma, 9 cases SFT (solitary fibrous tumor), 19 cases GIST (gastrointestinal stromal tumor), 12 cases Schwannoma and 13 cases neurofibroma which were retracted from the pathology files at Ain Shams University Hospitals with revision of all their available clinical data and available stained sections and then subjected to calretinin immunostain. Calretinin immunohistochemical expression was positive in 85.1% of deep fibromatosis cases including cases of desmoid tumor (18/20) and mesenteric fibromatosis (5/7) (48.1% patchy and 37% diffuse), 33.3% of LMS were presented by diffuse staining, 83.3% of schwannoma were presented by patchy staining. While all cases (100%) of MPNST, synovial sarcoma, SFT and GIST were negative for calretinin. Sensitivity was 85.2% and specificity 80.9% with positive predictive value 59% and negative predictive value 94%. Calretinin can be used to raise the diagnostic accuracy of fibromatosis versus other spindle cell lesions especially when MPNST, synovial sarcoma, SFT, and GIST are considered in the differential diagnosis.

Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies. We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF. We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination. Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.

Desmoid tumors, also called «agressive fibromatosis», are rare soft tissue tumors, locally invasives with a high recurrence tendency but non metastatic. They arise mainly in people with sporadic somatic CTNNB1 gene mutation or with history of trauma, surgery or during pregnancy. These tumors are often extra-abdominal but may also develop in the abdominal wall or, more rarely, in the mesentery or retroperitoneum. It is hard to distinguish local malignancy recurrence with another type of tumor such as desmoid tumor during the follow-up of intra-abdominal resected malignancy. Even if rare, desmoid tumors must be part of the differencial diagnosis, a fortiori in the context of a surgical history. Clinical behavior, high potential of local invasion and recurrency risk of the tumor must be at the center of the therapeutic decision. A conservative approach is totally justified at the price of a close clinical and radiological follow-up.

Desmoid-type fibromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of definitive treatments, and the chronic character of the disease can significantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. The most highly ranked issues by patients (n = 29) were issues concerning “tumour growth,” “feeling that there is something in the body that does not belong there,” and “fear of tumour growth into adjacent tissues or organs” with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1-4). HCPs (n = 31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8).

This study evaluates the results of the active surveillance (AS) approach in adult patients with desmoid-type fibromatosis (DTF) because AS is advocated as a front-line approach for DTF in the European consensus guidelines. A systematic literature search was conducted (December 19th, 2019, updated on April 14th, 2020). Studies describing the outcomes of the AS approach were included. The PRISMA guidelines were used. Twenty-five articles were included for data retrieval. Forty-two percent of reported patients (1480 of 3527 patients) received AS, the majority were women and the majority had a primary tumour. The median age at diagnosis ranged from 28 to 59 years. Common tumour sites were the extremities/girdles (n = 273), the abdominal wall (n = 253) and the trunk (n = 153). The median reported percentage of progressive disease, stable disease and partial response was 20% (interquartile range [IQR]: 13-35%), 59% (IQR: 37-69%) and 19% (IQR 3-23%), respectively. In 640 patients, the outcome was not specified. The median reported percentage of shifting to an active form of treatment was 29%, most commonly to systemic treatment (n = 195) and surgery (n = 107). The reported median follow-up time ranged between 8 and 73 months. The reported median time to progression and/or initiation of the subgroup shifting from AS to ‘active’ therapy ranged from 6.3 months to 19.7 months. The majority of patients undergoing AS have either stable disease or a partial response, and about one-third of patients shift to an active form of treatment. Selecting patients who will benefit from active surveillance upfront should be the priority of future studies.

We present a case of a desmoid tumor of the splenic hilum laparoscopically resected in a 70-year-old male with a previous history of chromophobe renal cell carcinoma and ocular spindle melanoma. Although benign, desmoid tumors might be infiltrative and produce serious complications. Treatment remains controversial, ranging from surgery and medical therapies to observation. Management of desmoid-type fibromatoses (DTFs) must be individualized, considering the risk of complications and recurrence.