Hidradenitis Suppurativa Complicated bySquamous Cell Carcinoma and ParaneoplasticNeuropathy

LAURA B. ROSENZWEIG, MD; ALLAN S. BRETT, MD; JEAN-FRANCOIS LEFAIVRE, MD;J.J. VANDERSTEENHOVEN, MD, PHD

ABSTRACT: Squamous cell carcinoma is a rare compli-cation of chronic, severe, hidradenitis suppurativa. Wedescribe a patient with a 20-year history of extensiveperineal hidradenitis suppurativa who presented withsubacute muscle weakness and sensory symptoms. Hewas subsequently diagnosed with squamous cell carci-noma arising in the area of hidradenitis. The neurologicsymptoms and signs resolved after complete excision of

the tumor. This presentation is consistent with a para-neoplastic neuropathy, which has not been reportedpreviously in patients with squamous cell carcinomaarising in patients with hidradenitis suppurativa. KEYINDEXING TERMS: Hidradenitis suppurativa; Carcino-ma; Squamous cell; Paraneoplastic polyneuropathy.[Am J Med Sci 2005;329(3):150–152.]

Hidradenitis suppurativa is a chronic inflamma-tory disorder of the apocrine glands that is

often progressive and debilitating.1 It is found mostcommonly in the axilla, perineum, external genita-lia, and inguinal regions. Many patients eventuallyrequire surgery, including incision and drainageprocedures and wide excisions.

Rarely, the chronic inflammation results in malig-nant transformation to squamous cell carcinoma.This complication occurs most commonly in the ano-genital region after several decades of disease. Inthis report, we present a patient with hidradenitissuppurativa for whom a presumed paraneoplasticneuropathy was the initial manifestation of malig-nant transformation. To our knowledge, this se-quence—a squamous cell carcinoma arising inhidradenitis suppurativa and manifesting as a para-neoplastic neuropathy—has not been describedpreviously.

Case Report

A 50-year-old man with a 20-year history of severe perinealhidradenitis suppurativa was hospitalized because of severalmonths of progressive lower extremity weakness. The weaknesshad worsened substantially during the previous week, and he was

no longer able to walk without assistance. Given the source ofinfection in the perineal region, the patient was hospitalizedbecause of concern for an epidural abscess.

During the previous 20 years, the patient had undergone nu-merous excisions of skin involved with hidradenitis, resulting ina left hemiscrotal resection and a diverting colostomy. Past med-ical history also included hypertension and gastroesophagealreflux for which he took quinapril, hydrochlorothiazide, and es-omeprazole. One month prior to admission, his family physicianprescribed prednisone (20 mg twice daily) and Augmentin (875mg twice daily) to treat chronic inflammation and infection asso-ciated with his hidradenitis. Two weeks prior to admission, thepatient noted several erythematous vesicular lesions bilaterallyon his extremities. An outpatient culture of a lesion was negativefor varicella-zoster virus, and the lesions resolved spontaneously.

Physical examination was unremarkable with the exception ofskin and neurologic findings. In the perineal region, the patienthad purulent drainage from sinus tracts with extensive granula-tion tissue and scarring (Fig. 1). No palpable lymph nodes werenoted in the cervical, axillary, or inguinal regions. Deep tendonreflexes were 2� throughout except for an absent left ankle jerk.Examination of the left leg revealed marked weakness of hipflexion and ankle dorsiflexion, and lesser weakness of other legmuscle groups. The right leg had mild weakness of all musclegroups. There was mild weakness of the triceps bilaterally withother arm muscle groups intact. No fasciculations, rigidity, orclonus were noted. Sensory examination revealed decreased lighttouch sensation diffusely over the left lower leg, not following anyspecific peripheral nerve or dermatome distribution. Pinpricksensation and proprioception were intact.

Routine laboratory study findings were normal except for ele-vated serum blood glucose (257 mg/dL) and elevated erythrocytesedimentation rate (86 mm/hr). Creatine kinase and thyroidstudy findings were normal. Magnetic resonance imaging studiesof the lumbosacral, thoracic, and cervical spine regions wereunremarkable. Analysis of cerebrospinal fluid revealed elevatedprotein (177 mg/dL), elevated glucose (147 mg/dL), no nucleatedcells, and negative culture and cytologic findings. Polymerasechain reaction testing of the cerebrospinal fluid was negative forcytomegalovirus, varicella-zoster virus, herpes simplex viruses 1and 2, Epstein-Barr virus, and mycobacterium tuberculosis.

From the Department of Medicine (LBR, ASB) and the Depart-ment of Surgery (J-FL), University of South Carolina School ofMedicine, and the Department of Pathology, Palmetto HealthRichland Hospital (JJV), Columbia, South Carolina

Submitted June 8, 2004; accepted August 31, 2004.Correspondence: Allan S. Brett, MD, University of South Caro-

lina School of Medicine, 2 Medical Park, Suite 502, Columbia, SC29203 (E-mail: abrett@sc.edu).

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Electromyography (conducted on the left leg) revealed in-creased insertional activity with decreased motor unit recruit-ment and fast firing in the tibialis anterior and peroneus longusmuscles, and increased insertional activity in the biceps femorismuscle. These findings were consistent with a polyneuropathy; nomyopathic features were present.

Prednisone was stopped on admission, and regular insulincoverage was initiated. Bilateral leg weakness progressed, andthe patient was unable to bear weight after 1 week in thehospital. Because of concern about malignant transformation ofthe hidradenitis suppurativa, a plastic surgeon was consulted. Onhospital day 9, the patient underwent surgical excision of peri-neal tissue that was thought to be suspicious for malignancy.Pathologic examination revealed extensive invasive well-differ-entiated keratinizing squamous cell carcinoma (Fig. 2). Pelviccomputed tomography and magnetic resonance imaging scanswere negative for metastasis and neural invasion. On hospitalday 17, the patient underwent a wider local excision, whichrevealed additional areas of squamous cell carcinoma. The sur-geon was concerned that this second procedure was not curativebecause of narrow histopathologic margins. Thus, a third surgerywas performed 3 weeks later, with excision of additional tissue atthe right inner thigh and groin.

Starting a few days after the first surgery and continuing overthe next month, the patient’s strength improved rapidly, dyses-thesias disappeared, and the patient regained the ability to am-bulate without difficulty. Eighteen months later, there is noevidence of tumor recurrence, neurologic examination findingsremain normal, and the patient is fully functional. During thisperiod, he underwent debridement and skin grafting on twooccasions (3 and 6 months after his initial presentation). He stillhas small open draining areas of hidradenitis but has declinedadditional surgery.

Discussion

This case demonstrates two uncommon diseaseentities, squamous cell carcinoma arising in hidra-denitis suppurativa and a probable paraneoplasticsyndrome associated with cutaneous squamous cellcancer. To our knowledge, this is the first reportedcase of a cutaneous squamous cell cancer presentingwith a paraneoplastic neuropathy.

Paraneoplastic syndromes refer to signs andsymptoms resulting from the effects of tumor on

distant organ systems. The tumor is postulated togenerate growth factors, hormones, antibodies, an-tigens, and other substances that may affect endo-crine, hematologic, or neurologic function. Paraneo-plastic disorders may herald the presence ofmalignancy, and successful treatment of the malig-nancy usually abolishes paraneoplastic signs andsymptoms.

Although commonly associated with internal tu-mors, paraneoplastic syndromes have been reportedrarely with cutaneous malignancies. Paraneoplasticophthalmoplegia and motor neuropathy has beendescribed in association with melanoma.2 Bazexsyndrome (a paraneoplastic disorder characterizedby palmoplantar hyperkeratosis and psoriasiformrash)3 and paraneoplastic hypercalcemia have beenreported with cutaneous squamous cell carcino-

Figure 1. Extensive perineal hidradenitis suppurativa, withscarring, granulation tissue, and sinus tracts.

Figure 2. (A) Microscopically, keratinizing squamous cell carci-noma is present along the surface with extension into the under-lying dermis (H&E; magnification, 100�). (B) Higher magnifica-tion illustrates central keratinization, marked cellularpleomorphism, and mitotic activity (H&E; magnification, 400�).

Rosenzweig et al

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ma.4–6 In two of the reports of hypercalcemia, thecancer occurred in a patient with hidradenitissuppurativa.5,6

Neurologic paraneoplastic syndromes can involvethe brain and cranial nerves, spinal cord, dorsal-rootganglia, peripheral nerves, and neuromuscularjunctions.7 We believe that our patient experienceda paraneoplastic neuropathy associated with cuta-neous squamous cell carcinoma that complicatedhidradenitis suppurativa. His clinical improvementafter excision of the tumor is a hallmark of paraneo-plastic syndromes. Initially, we considered severalother diagnoses. Epidural abscess was excluded byimaging. A myopathy was excluded by the presenceof both motor and sensory symptoms, a normal cre-atine kinase level, and the absence of myopathicabnormalities on electrodiagnostic testing. More-over, steroid myopathy was implausible becauseweakness had begun prior to the recent course ofprednisone. The increased insertional activity anddecreased motor unit recruitment supported a neu-ropathic process. Varicella-zoster has been associ-ated with sensory and motor neuropathies8; how-ever, a cerebrospinal fluid polymerase chainreaction test yielded negative results, viral cultureof previous unexplained skin lesion was negative,and the symptoms antedated the skin lesions byseveral months. We also considered diabetic amyo-trophy because of the elevated blood glucose level onadmission. However, hyperglycemia resolved afterprednisone was stopped, and the patient had noprevious history of diabetes. A brief episode of ste-roid-induced hyperglycemia is unlikely to havecaused this degree of neuropathy.

In summary, this case is most consistent withparaneoplastic neuropathy as a presenting manifes-tation of cutaneous squamous cell cancer arising inan area of chronic hidradenitis suppurativa. We

cannot exclude with absolute certainty a viral ornonparaneoplastic metabolic cause to explain thispatient’s findings. However, the prompt improve-ment after excision of the tumor, and our inability toidentify another plausible cause, strongly suggest aparaneoplastic origin. Physicians should be alert tothe possibility of malignant transformation in casesof chronic extensive hidradenitis suppurativa andshould consider occult malignancy when they en-counter unexplained neuropathy.

References

1. Brown TJ, Rosen T, Orengo IF. Hidradenitis suppurativa.South Med J 1998;91:1107–14.

2. Kloos L, Sillevis Smitt P, Ang CW, et al. Paraneoplasticophthalmoplegia and subacute motor axonal neuropathy asso-ciated with anti-GQ1b antibodies in a patient with malignantmelanoma. J Neurol Neurosurg Psychiatry 2003;74:507–9.

3. Hara M, Hunayama M, Aiba S, et al. Acrokeratosis para-neoplastica (Bazex syndrome) associated with primary cuta-neous squamous cell carcinoma of the lower leg, vitiligo andalopecia areata. Br J Dermatol 1995;133:121–4.

4. Cisneros G, Lara LF, Crock R, et al. Humoral hypercalce-mia of malignancy in squamous cell carcinoma of the skin:parathyroid hormone-related protein as a cause. South Med J2001;94:329–31.

5. Welsh DA, Powers JS. Elevated parathyroid hormone-re-lated protein and hypercalcemia in a patient with cutaneoussquamous cell carcinoma complicating hidradenitis suppura-tiva. South Med J 1993;86:1403–4.

6. Sparks MK, Kuhlman DS, Prieto A, et al. Hypercalcemia inassociation with cutaneous squamous cell carcinoma: occur-rence as a late complication of hidradenitis suppurativa. ArchDermatol 1985;121:243–6.

7. Darnell RB, Posner JB. Paraneoplastic syndromes involvingthe nervous system. N Engl J Med 2003;349:1543–54.

8. Mondelli M, Romano C, Rossi S, et al. Herpes zoster of thehead and limbs: electroneuromyographic and clinical findingsin 158 consecutive cases. Arch Phys Med Rehabil 2002;83:1215–21.

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