Malignant acanthosis nigricans with occult primary

Introduction

Acanthosis nigricans (AN) is characterized by velvety, hyperpigmented, verrucous, symmetric and occasionally pruritic plaques which have a predilection for flexural areas.[1] In extreme cases, nearly the entire skin surface may be involved. Unna proposed the name "acanthosis nigricans (acantho, from the Greek for "thorn" and nigricans, from the Latin, "becoming black").[2] Schwartz described eight types of acanthosis nigricans: benign, obesity associated, syndromic, malignant, acral, unilateral, medication-induced and mixed type.[3] Malignant acanthosis nigricans (a paraneoplastic syndrome) is much less common than the other types and has a generally poor prognosis, which atleast in part is related to the low survival rate from the neoplasia concerned.[3] We report a 39 year-old woman with extensive cutaneous, oral and vulval AN, required hypertrichosis lanuginose and florid cutaneous papillomatosis in association with signet cell adenocarcinoma from an unknown primary site.

Case Report

A 39-year-old lady presented with history of progressive hyperpigmentation and thickening of the skin, all over the body, associated with pruritus, of two years′ duration. The lesions appeared initially in the cubital fossae, but soon spread to involve the whole body within a span of few months. She had no other complaints like loss of appetite or weight or melena. There was no history of drug intake, endocrine abnormalities or menstrual irregularities. The family members were unaffected. Examination re-vealed mild pallor and en-larged left su-praclavicular lymph nodes. There was hy-perpigmenta-tion and thick-ening of the skin with a vel-vety texture all over the body with accentua-tion in the flex-ures. She had multiple warty excrescences over the rug-ose skin on the face, nasal cavity and trunk (cutane-ous papilloma-tosis). On the face, in addi-tion, she also had fine lanugo hairs typical of hy-pertrichosis lanuginose [Figure - 1]. There were papillo-matous growths on the vulval mucosa and lips and the entire hard palate was covered with fleshy verru-cous plaques [Figure - 2]. She also had the characteristic pachy-dermatoglyphy Examination of the other sys-tems including per rectal and per vaginal examination, was unreward-ing.

Inve-stigations revealed low hemoglobin (9.9 gm%), raised ESR-(105mm/1st hr) and hypochromic anemia. Chestx-ray was also within normal limits. Stool occult blood was negative. Skin biopsy showed hyperkeratosis papillomatosis and mild acanthosis. [Figure - 3].

Fine needle aspiration cytology of the left supraclavicular lymph node showed metastasis from mucin secreting adenocarcinoma of the sig-net ring cell type [Figure - 4]. Abdominal ultrasonog-raphy (USG) revealed multiple peripancreatic, left common iliac and left external iliac lymph nodes. Transvaginal USG was normal. Carcinoembryonic antigen showed 20-fold increase. Oesophago-gastro-duodenoscopywas attempted, but failed as the patient was not co-operative. Contrast com-puterized tomography scan of the abdomen and pelvis showed enlargement of mesenteric, retrocrural and retroperitoneal lymph nodes with ascites but no primary malignancy could be de-tected.

Discussion

Malignant AN is usually seen in older individuals and it has sudden onset with rapid progression and extensive involvement with accompanying pruritus.[3] Hyperkeratosis with roughened thickening of the fingerprints (pachydermatoglyphy) with prominence of the creases and yellow hue, may occur in malignant acanthosis nigricans.[2] Malignant acanthosis nigricans most likely results from the secretion of tumour products with insulin-like growth factor activity at the cell receptor level.[4] Transforming growth factor-alpha is also postulated to have a role in its pathogenesis.[5] Malignant AN can coexist with other cutaneous markers of internal malignancy like the sign of Leser-Trelat,[4] florid cutaneous papillomatosis[4],[5],[6] and hypertrichosis lanuginose.[6]

Malignant AN can rarely precede the detection of malignancy by 6 to 16 years, but it usually occurs simultaneously with the malignancy.[1] It is most commonly associated with adenocarcinoma of the stomach though it can also be seen with carcinoma of the pancreas, colon, ovary, prostate, breast and lung.[1] If the diagnosis of malignant acanthosis nigricans is suspected, a vigorous effort must be made to identify the responsible tumour.[3] In rare instances the malignancy can evade all the possible investigations, so that one has to finally resort to exploratory Iaparotomy[4] and when that is not possible, the tumor can be demonstrated only by postmortem examination.[1] Sometimes even this can be unsuccessful.[7]

Our patient had all the typical features of malignant acanthosis nigricans along with acquired hypertrichosis Ianuginose and florid cutaneous papillomatosis in the presence of widespread metastases, but the search for the primary malignancy was unrewarding. Another interesting feature was that inspite of the extensive AN persisting for the past two years and the extensive metastases, she was completely asymptomatic regarding the primary malignancy. Our case highlights the coexistence of these cutaneous markers of internal malignancy thereby necessitating a thorough search for the underlying primary malignancy. The primary malignancy in our patient remains occult in every sense i.e without any overt symptoms or any specific clinical or laboratory evidence. This is a presentation, that to the best of our knowledge, has not been previously reported from India.