Malignant granular cell tumor of the anal-perianal region and suprarenal hyperplasia: a casual association?

Sir,

The granular cell tumor (GCT), although originally considered a muscle tumor by Abrikossoff,[1] is now firmly identified as a neural lesion since its close association with nerve and immunohistochemical characteristics.[23]

We report the case of a 66-year-old man who presented to our department for an about 6-month history of an itching and burning solitary cutaneous nodule of the anal-perianal region; patient referred that the lesion was rapidly growing in the past 3 months. Physical examination showed a tender ruberry, round-oval-shaped nodule measuring about 5 cm × 3 cm with a smooth surface and mobile on the subcutaneous planes [Figure 1]. There was no palpable lymph node, and the patient suffered from hypertension for several years. Routine laboratorial tests and chest X-ray were performed without alterations. An incision biopsy specimen showed cutis with a proliferation of voluminous cells in the reticular dermis [Figure 2]. At higher magnification, the cells showed a coarsely granular cytoplasm [Figure 3]; furthermore, necrosis, high nucleo-cytoplasmic ratio, cellular pleomorphism, and vesicular nuclei with prominent nucleoli were observed. Immunohistochemically, tumor cells showed positivity for S-100 [Figure 4] protein and neurone-specific enolase [NSE; Figure 5] whereas laminin, cromogranin, and ACTH were negative. On the basis of physical examination, histopathological, and immunohistochemical findings, a diagnosis of malignant GCT was reached.. The neoplasm was excised completely, and several tests such as abdominal CT scan and colonoscopy were performed to exclude the presence of possible metastases. CT showed bilateral hyperplasia of the suprarenal glands and to rule out primary or secondary hyperadrenocorticism, plasma ACTH level and urinary glucocorticoid, and mineralcorticoid levels were evaluated. The results showed an increase of plasma ACTH level (98.1 pg/mL; normal level <46 pg/mL) and urinary-free cortisol level (990.5 nmol/day; normal level 153-789 nmol/day). Furthermore, skull X-ray and CT scan were performed without alterations and the patient was asymptomatic, without signs of hypercortisolism (Cushing's syndrome).

Figure 1

The itching and burning solitary cutaneous nodule of the anal-perianal region of about 5 cm × 3 cm

Figure 2

Histopathological examination showed cutis with a proliferation of voluminous cells in the reticular dermis (H and E staining, ×100)

Figure 3

At higher magnification, the cells showed a coarsed granular cytoplasm (H and E staining, ×400)

Figure 4

Immunohistochemical examination showed positivity for S-100 protein (×200)

Figure 5

Immunohistochemical examination showed positivity for NSE. Both NSE and S-100, like most nerve sheath-derived neoplasms, are hyper-expressed in the GCT (×200)

GCT is regarded as a benign uncommon soft neoplasm of nerve sheath origin and derives its name from the coarse cytoplasmic granularity that is typically found among its constituent cells. GCT can develop in any location with predilection for the head and neck region, especially the tongue; GCT can also be founded in the internal organs particularly the larynx, bronchus, stomach, and bile ducts.[4] Approximately, 10-25% of patients have lesions at multiple sites, and new lesions may appear synchronously or over a period of many years. The histopathological findings of GCT are a noncapsulated group of spindle and plump cells with coarse granular eosinophilic cytoplasm from which derives its name.[2] Ultrastructural studies have demonstrated the cytoplasmatic granules to be lysosomes and are similar to the lysosomes found within Schwann cells that have ingested myelin. Similar to most nerve sheath-derived neoplasms, GCT is notable for its constant and diffuse positivity for S-100 antigen and NSE. It is important to evaluate the presence of some characteristics as necrosis, spindling, vescicular nuclei with prominent nucleoli, increased mitotic activity (>2 mitoses/10 HPF), high nucleo-cytoplasmic ratio, and pleomorphism; in the case of three or more of these histopathological findings, the neoplasm can be considered as a malignant variant of GCT. Only 1–2% of GCT are malignant, and their appearance in the lung, liver, bone, and limph node are common. Bouraoui et al.[5] and Mnasri and Bouchoucha[6] were the first to describe a case of malignant GCT of the anal region. Other than these two reports, we have not found any other reports on occurrence of this type of malignancy in anal region. Moreover, in our patient we found a bilateral suprarenal hyperplasia associated with an increase of plasmatic ACTH level and urinary-free cortisol level. An hypothesis of the associated hypercortisolism could be an excreting ACTH adenoma of pituitary gland that we exclude since skull X-ray and CT scan showed no alterations. Another hypothesis could be a “paraneoplastic” syndrome linked to an abnormal and ectopic secretion of ACTH probably related to the malignant GCT; since the negativity of immunohistochemical examination for ACTH and the persistence of elevated levels of plasmatic ACTH and urinary-free cortisol even after the tumor excision in the absence of instrumental detectable metastases that we can exclude this hypothesis. Probably, the asymptomatic secondary hypercortisolism is linked to an occult ectopic production of ACTH in an anatomic site and from cells that we are not able to identify. In conclusion, we describe the first case of association between the rare malignant GCT of the anal-perianal region with an idiopathic suprarenal hyperplasia and hypercortisolism. We found difficult to establish if it is only a casual association or if there is a fine link between these diseases and only more reports could help to remove the dilemma.