Nodular granular muscle degeneration of the appendix and obesity.

Granular muscle degeneration (GMD) of the appendix is rare. Although first described in 1959, the histogenesis of this lesion remains incompletely elucidated.[123] We report in this paper, a case of nodular GMD diagnosed incidentally in an appendix resected for the treatment of acute abdominal pain.

The 39-year-old, afebrile woman presented with acute abdominal pain and amenorrhea. The patient's mother had arterial hypertension and diabetes. The patient's personal history included an anal abscess (16 years previously) and, more recently, an increase in body weight with facio-truncal obesity (30 kg in 12 months, body mass index ranges 39-40.2), umbilical hernia, hirsutism, and axillary acanthosis nigricans. Three years previously, the patient had had an spontaneous abortion, with amenorrhea alternating with spotting, which was treated by dydrogesterone. Blood tests showed fluctuant hypercholesterolemia and hyperprolactinemia with normal big-big-prolactin, follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, thyroid hormones, cortisol, and glucose. A normal hypophysis was seen on MRI. Computed tomography indicated incipient appendicitis and a diffusely enlarged (12 × 7 × 6 cm) uterus with uterine body myomatous necrobiotic aspects. Appendectomy was performed. At 40 days postoperatively, the patient was well. The appendix measured 6.5 cm and did not show any macroscopic lesion. The entire appendix was analyzed microscopically. The appendiceal wall showed lymphoid follicular hyperplasia and submucosal fibrosis with mild inflammation [Figure 1]. A 3-mm plurilobar nodular lesion was observed in the inner muscle layer at 1 cm from the tip. The lesion was deforming the muscle layer and was prominent in the submucosa, which showed diffuse fibrosis with mild inflammation. The lobules were round-oval, with a focal rim of surrounding collagen. They were composed of large round and polygonal cells. These cells showed abundant pale-pink eosinophilic granular cytoplasm and rare round eosinophilic bodies of megamitochondria type. The nuclei, round-to-oval, showed focal irregularities. They were larger and normo- or hypochromic as compared to the surrounding muscle. The nuclear/cytoplasm ratio was low. No mitoses were seen. One glycogenated nucleus was observed. A total of 205 granular-appearing cells were counted (with 51 nuclei) on the hematoxylin-and-eosin stained section. Rare compressed interspersed atrophic muscle cells were seen between 2 of the lobules at the periphery of the lesion. Perilesional muscle cells were compressed. The overlying mucosa was normal. On immunohistochemistry, the granular cells expressed smooth-muscle-actin and desmin. Both proteins showed cytoplasmic expression with perimembrane/membrane reinforcement. Perinuclear accumulation for desmin was also observed. CD34, CD117, S100 protein, chromogranin, and synaptophysin were not expressed by the granular cells.

Figure 1

(A-D) The appendiceal intramuscular nodule consisted in large, polygonal cells with granular cytoplasm. (B: Arrows for mega-mitochondria-type globules. C arrow for glycogenic nucleus). They expressed smooth-muscle-actin (Dinset) and desmin (D) in a cytoplasmic/perimembranous, or perinuclear pattern (D: Arrow). Original magnification ×2.5 (A) ×40 (B-D)

Once the smooth-muscle-actin- and desmin-positive immunophenotype of the lesion was established, the main differential diagnoses were appendiceal smooth muscle lesions, in spite of the morphological resemblance to neural ganglion or granular cell tumor cells on standard stains. The diagnoses of leiomyomatosis and uterine leiomyosarcoma metastasis were not retained on the basis of the morphological features, although the patient showed a diffusely enlarged uterus characterized as “myomatous” at radiological examination. We did not favor the hypothesis of diabetic myopathy[4] either since the patient's blood glucose level was normal. The presence of a plurilobular architecture, the lack of veritable stroma, and the presence of a round and polygonal (rather than spindle) cell morphology, as well as the presence of glycogenated nucleus and cytoplasmic globules of megamitochondria type (similar to those described in obesity hepatocytes), were interpreted as being suggestive of GMD-type lesions rather than of microleiomyoma, despite the perinodular compression effect. Of interest was the patient's weight gain with obesity since GMD is thought to occur by cytoplasmic liposomal accumulation.[123] The staining pattern we have observed supported this hypothesis, with a cytoplasmic perimembraneous and perinuclear concentration of the smooth muscle actin- and desmin-positive intermediate filaments. GMD has been compared in the past to Masson's granular myoblastoma.[2] Moreover, the current knowledge does not allow us to completely rule out the hypothesis of an incipient leiomyoma, prominent in the submucosa and deforming the muscle layer, with GMD, this association being already reported in uterine leiomyoma, however voluminous (5 cm).[5]

In conclusion, here we report a case of appendiceal nodular muscular granular degeneration that was incidentally diagnosed in an obese patient. Immunohistochemical phenotyping is required for a differential diagnosis, although morphological features such as glycogenic nuclei and cytoplasmic megamitochondria might be suggestive of such lesions.